研究者詳細 - 長﨑正朗

お知らせ

写真a

ナガサキ　マサオ

長﨑正朗

NAGASAKI MASAO

所属

生体防御医学研究所附属高深度オミクスサイエンスセンター教授
生体防御医学研究所附属高深度オミクスサイエンスセンター（併任）
システム生命科学府システム生命科学専攻（併任）
医学系学府医科学専攻（併任）

電話番号

0926424815

プロフィール

生体防御医学研究所附属高深度オミクスサイエンスセンターに所属し、バイオメディカル情報解析分野を主宰している。

ホームページ

https://nagasakilab.csml.org/

外部リンク

研究分野

ライフサイエンス / ゲノム生物学

研究テーマ・研究キーワード

研究テーマ：大規模情報解析

研究キーワード：大規模情報解析

研究期間： 2024年
研究テーマ：バイオメディカルインフォマティクス

研究キーワード：バイオメディカルインフォマティクス

研究期間： 2024年
研究テーマ：バイオインフォマティクス

研究キーワード：バイオインフォマティクス

研究期間： 2024年
研究テーマ：ヒトを中心としたゲノム、オミクス情報、また、臨床情報の大規模情報について情報解析を展開できる次世代かつ即戦力となるデータサイエンス時代の人材を育成

研究キーワード：バイオインフォマティクス、メディカルインフォマティクス、大規模情報解析

研究期間： 2023年4月

受賞

最優秀論文賞

2017年8月情報処理学会DICOMO2017実行委員会プライバシ保護ゲノム解析のための秘密計算フィッシャー正確検定の実装評価
IEEE BioVis 2011 Contest Award

2011年10月 IEEE (The Institute of Electrical and Electronics Engineers, Inc.)

論文

Mutations of CYP1B1 and FOXC1 genes for childhood glaucoma in Japanese individuals

Fuse N., Kimura M., Shimizu A., Koshiba S., Hamanaka T., Nakamura M., Ishida N., Sakai H., Ikeda Y., Mori K., Endo A., Nagasaki M., Katsuoka F., Yasuda J., Matsubara Y., Nakazawa T., Yamamoto M.

Japanese Journal of Ophthalmology 2024年8月（ ISSN:0021-5155 ）

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記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Japanese Journal of Ophthalmology

Purpose: To explore the frequency and positions of genetic mutations in CYP1B1 and FOXC1 in a Japanese population. Study design: Molecular genetic analysis. Methods: Genomic DNA was extracted from 31 Japanese patients with childhood glaucoma (CG) from 29 families. We examined the CYP1B, FOXC1, and MYOC genes using Sanger sequencing and whole-exome sequencing (WES). Results: For CYP1B1, we identified 9 families that harbored novel mutations, p.A202T, p.D274E, p.Q340*, and p.V420G; the remaining mutations had been previously reported. When mapped to the CYP1B1 protein structure, all mutations appeared to influence the enzymatic activity of CYP1B1 by provoking structural deformity. Five patients were homozygotes or compound heterozygotes, supporting the recessive inheritance of the CYP1B1 mutations in CG. In contrast, four patients were heterozygous for the CYP1B1 mutation, suggesting the presence of regulatory region mutations or strong modifiers. For the FOXC1 gene, we identified 3 novel mutations, p.Q23fs, p.Q70R, and p.E163*, all of which were identified in a heterozygous state. No mutation was found in the MYOC gene in these CG patients. All individuals with CYP1B1 and FOXC1 mutations were severely affected by early-onset CG. In the CYP1B1-, FOXC1-, and MYOC-negative families, we also searched for variants in the other candidate genes reported for CG through WES, but could not find any mutations in these genes. Conclusions: Our analyses of 29 CG families revealed 9 families with point mutations in the CYP1B1 gene, and four of those patients appeared to be heterozygotes, suggesting the presence of complex pathogenic mechanisms. FOXC1 appears to be another major causal gene of CG, indicating that panel sequencing of CYP1B1 and FOXC1 will be useful for diagnosis of CG in Japanese individuals.

DOI： 10.1007/s10384-024-01103-0

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Genetically Predicted Higher Levels of Caffeic Acid Are Protective Against Ulcerative Colitis: A Comprehensive Metabolome Analysis

Naito, T; Osaka, R; Kakuta, Y; Kawai, Y; Khor, SS; Umeno, J; Tokunaga, K; Nagai, H; Shimoyama, Y; Moroi, R; Shiga, H; Nagasaki, M; Kinouchi, Y; Masamune, A

INFLAMMATORY BOWEL DISEASES 2024年6月（ ISSN:1078-0998 eISSN:1536-4844 ）

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記述言語：英語

DOI： 10.1093/ibd/izae143

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Identification of the hybrid gene <i>LILRB5-3</i> by long-read sequencing and implication of its novel signaling function

Hirayasu, K; Khor, SS; Kawai, Y; Shimada, M; Omae, Y; Hasegawa, G; Hashikawa, Y; Tanimoto, H; Ohashi, J; Hosomichi, K; Tajima, A; Nakamura, H; Nakamura, M; Tokunaga, K; Hanayama, R; Nagasaki, M

FRONTIERS IN IMMUNOLOGY 15 1398935 2024年5月（ ISSN:1664-3224 ）

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記述言語：英語出版者・発行元：Frontiers in Immunology

Leukocyte immunoglobulin (Ig)-like receptors (LILRs) on human chromosome 19q13.4 encode 11 immunoglobulin superfamily receptors, exhibiting genetic diversity within and between human populations. Among the LILR genes, the genomic region surrounding LILRB3 and LILRA6 has yet to be fully characterized due to their significant sequence homology, which makes it difficult to differentiate between them. To examine the LILRB3 and LILRA6 genomic region, a tool named JoGo-LILR CN Caller, which can call copy number from short-read whole genome sequencing (srWGS) data, was applied to an extensive international srWGS dataset comprising 2,504 samples. During this process, a previously unreported loss of both LILRB3 and LILRA6 was detected in three samples. Using long-read sequencing of these samples, we have discovered a novel large deletion (33,692 bp) in the LILRB3 and LILRA6 genomic regions in the Japanese population. This deletion spanned three genes, LILRB3, LILRA6, and LILRB5, resulting in LILRB3 exons 12-13 being located immediately downstream of LILRB5 exons 1-12 with the loss of LILRA6, suggesting the potential expression of a hybrid gene between LILRB5 and LILRB3 (LILRB5-3). Transcription and subsequent translation of the LILRB5-3 hybrid gene were also verified. The hybrid junction was located within the intracellular domain, resulting in an LILRB5 extracellular domain fused to a partial LILRB3 intracellular domain with three immunoreceptor tyrosine-based inhibitory motifs (ITIMs), suggesting that LILRB5-3 acquired a novel signaling function. Further application of the JoGo-LILR tool to srWGS samples suggested the presence of the LILRB5-3 hybrid gene in the CEU population. Our findings provide insight into the genetic and functional diversity of the LILR family.

DOI： 10.3389/fimmu.2024.1398935

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Precise immunofluorescence canceling for highly multiplexed imaging to capture specific cell states

Tomimatsu, K; Fujii, T; Bise, R; Hosoda, K; Taniguchi, Y; Ochiai, H; Ohishi, H; Ando, K; Minami, R; Tanaka, K; Tachibana, T; Mori, S; Harada, A; Maehara, K; Nagasaki, M; Uchida, S; Kimura, H; Narita, M; Ohkawa, Y

NATURE COMMUNICATIONS 15 ( 1 ) 3657 2024年5月（ eISSN:2041-1723 ）

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記述言語：英語出版者・発行元：Nature Communications

Cell states are regulated by the response of signaling pathways to receptor ligand-binding and intercellular interactions. High-resolution imaging has been attempted to explore the dynamics of these processes and, recently, multiplexed imaging has profiled cell states by achieving a comprehensive acquisition of spatial protein information from cells. However, the specificity of antibodies is still compromised when visualizing activated signals. Here, we develop Precise Emission Canceling Antibodies (PECAbs) that have cleavable fluorescent labeling. PECAbs enable high-specificity sequential imaging using hundreds of antibodies, allowing for reconstruction of the spatiotemporal dynamics of signaling pathways. Additionally, combining this approach with seq-smFISH can effectively classify cells and identify their signal activation states in human tissue. Overall, the PECAb system can serve as a comprehensive platform for analyzing complex cell processes.

DOI： 10.1038/s41467-024-47989-9

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A genome-wide association study identified <i>PTPN2</i> as a population-specific susceptibility gene locus for primary biliary cholangitis 国際誌

Hitomi, Y; Ueno, K; Aiba, Y; Nishida, N; Kono, M; Sugihara, M; Kawai, Y; Kawashima, M; Khor, SS; Sugi, K; Kouno, H; Kouno, H; Naganuma, A; Iwamoto, S; Katsushima, S; Furuta, K; Nikami, T; Mannami, T; Yamashita, T; Ario, K; Komatsu, T; Makita, F; Shimada, M; Hirashima, N; Yokohama, S; Nishimura, H; Sugimoto, R; Komura, T; Ota, H; Kojima, M; Nakamuta, M; Fujimori, N; Yoshizawa, K; Mano, Y; Takahashi, H; Hirooka, K; Tsuruta, S; Sato, T; Yamasaki, K; Kugiyama, Y; Motoyoshi, Y; Suehiro, T; Saeki, A; Matsumoto, K; Nagaoka, S; Abiru, S; Yatsuhashi, H; Ito, M; Kawata, K; Takaki, A; Arai, K; Arinaga, T; Abe, M; Harada, M; Taniai, M; Zeniya, M; Ohira, H; Shimoda, S; Komori, A; Tanaka, A; Ishigaki, K; Nagasaki, M; Tokunaga, K; Nakamura, M

HEPATOLOGY 80 ( 4 ) 776 - 790 2024年4月（ ISSN:0270-9139 eISSN:1527-3350 ）

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1097/HEP.0000000000000894

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rs10924104 in the expression enhancer motif of CD58 confers susceptibility to human autoimmune diseases 国際誌

Hitomi, Y; Ueno, K; Aiba, Y; Nishida, N; Kawai, Y; Kawashima, M; Khor, SS; Takada, S; Iwabuchi, C; Nagasaki, M; Tokunaga, K; Nakamura, M

HUMAN GENETICS 143 ( 1 ) 19 - 33 2024年1月（ ISSN:0340-6717 eISSN:1432-1203 ）

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記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Human Genetics

CD58 plays roles in cell adhesion and co-stimulation with antigen presentation from major histocompatibility complex class II on antigen-presenting cells to T-cell antigen receptors on naïve T cells. CD58 reportedly contributes to the development of various human autoimmune diseases. Recently, genome-wide association studies (GWASs) identified CD58 as a susceptibility locus for autoimmune diseases such as systemic lupus erythematosus (SLE), multiple sclerosis (MS), and primary biliary cholangitis (PBC). However, the primary functional variant and molecular mechanisms of susceptibility to autoimmune diseases in the CD58 locus were not clarified. Here, rs10924104, located in the ZNF35-binding motif within the gene expression regulatory motif, was identified as the primary functional variant for SLE, MS, and PBC among genetic variants showing stronger linkage disequilibrium (LD) with GWAS-lead variants in the CD58 locus. Expression-quantitative trait locus (e-QTL) data for each distinct blood cell type and in vitro functional analysis using the CRISPR/Cas9 system corroborated the functional role of rs10924104 in the upregulation of CD58 transcription by the disease-risk allele. Additionally, the strength of disease susceptibility observed in the CD58 locus could be accounted for by the strength of LD between rs10924104 and each GWAS-lead variant. In conclusion, the present study demonstrated for the first time the existence of a shared autoimmune disease-related primary functional variant (i.e., rs10924104) that regulates the expression of CD58. Clarifying the molecular mechanism of disease susceptibility derived from such a shared genetic background is important for understanding human autoimmune diseases and human immunology.

DOI： 10.1007/s00439-023-02617-2

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High-risk pathogenic germline variants in blood relatives of BRCA1/2 negative probands

Yoshida R., Kaneyasu T., Ueki A., Yamauchi H., Ohsumi S., Ohno S., Aoki D., Baba S., Kawano J., Matsumoto N., Nagasaki M., Ueno T., Inari H., Kobayashi Y., Takei J., Gotoh O., Nishi M., Okamura M., Kaneko K., Okawa M., Suzuki M., Amino S., Inuzuka M., Noda T., Mori S., Nakamura S.

Breast Cancer 2024年（ ISSN:13406868 ）

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出版者・発行元：Breast Cancer

Background: Tailored, preventive cancer care requires the identification of pathogenic germline variants (PGVs) among potentially at-risk blood relatives (BRs). Cascade testing is carried out for BRs of probands who are positive for PGVs of an inherited cancer but not for negative probands. This study was conducted to examine the prevalence of PGVs for BRs of PGV-negative probands. Methods: PGV prevalence was assessed for 682 BRs of 281 probands with BRCA1/BRCA2 wild-type hereditary breast and ovarian cancer (HBOC) syndrome. Results: PGVs were discovered in 22 (45.8%) of the 48 BRs of the PGV-positive probands and in 14 (2.2%) of 634 BRs of the PGV-negative probands. Eleven PGVs on high-risk BRCA1, BRCA2, and TP53 genes were present only in BRs and not in the probands (probands vs BRs in Fisher exact test; p = 0.0104; odds ratio [OR] = 0.000 [0.000–0.5489 of 95% confidence interval]), partly due to the nature of the selection criteria. The enrichment of high-risk PGVs among BRs was also significant as compared with a non-cancer East Asian population (p = 0.0016; OR = 3.0791 [1.5521–5.6694]). PGV prevalence, risk class of gene, and genotype concordance were unaffected by the cancer history among BRs. Conclusion: These findings imply the necessity to construct a novel testing scheme to complement cascade testing.

DOI： 10.1007/s12282-024-01615-0

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The Results of Genetic Analysis and Clinical Outcomes after Stent Deployment in Adult Patients with Isolated Peripheral Pulmonary Artery Stenosis 招待査読国際誌

M. Kanezawa, H. Shimokawahara, M. Tsuji, K. Suruga, A. Miyagi, M. Marunaka, T. Mukai, T. Kawaguchi, T.Y. Yang, I. Yamaguchi, M. Nagasaki, F. Matsuda, H. Matsubara

Eur Respir J 2023年11月

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記述言語：日本語掲載種別：研究論文（学術雑誌）
Analysis of Genetic Polymorphism of Bitter Taste Receptor TAS2R38 and TAS2R46, and Its Relationship with Eating and Drinking Habits in Japanese ToMMo Subjects 招待査読国際誌

M. Yamaki, H. Saito, T. Mimori, Y. Suzuki, M. Nagasaki, K. Suzuki, S. Satoh-Kuriwada, N. Shoji, K. Isono, T. Goto, H. Shirakawa, M. Komai

J Nutr Sci Vitaminol 2023年11月

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記述言語：日本語掲載種別：研究論文（学術雑誌）
抗原提示補助シグナル分子の遺伝的バリアントに起因する自己免疫疾患感受性の分子機序の解明

人見祐基, 植野和子, 相葉佳洋, 西田奈央, 河合洋介, 川嶋実苗, Khor Seik-Soon, 長崎正朗, 徳永勝士, 中村稔

MHC: Major Histocompatibility Complex 30 ( 2Suppl. ) 83 - 83 2023年9月（ ISSN:2186-9995 eISSN:2187-4239 ）

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記述言語：日本語出版者・発行元：(一社)日本組織適合性学会

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HLA-DQA1*05 and upstream variants of PPARGC1B are associated with infliximab persistence in Japanese Crohn's disease patients 国際誌

Shimoda, F; Naito, T; Kakuta, Y; Kawai, Y; Tokunaga, K; NCBN Controls WGS Consortium; Shimoyama, Y; Moroi, R; Shiga, H; Nagasaki, M; Kinouchi, Y; Masamune, A; Ishibashi-Ueda, H; Tomita, T; Noguchi, M; Takahashi, A; Goto, YI; Yoshida, S; Hattori, K; Matsumura, R; Iida, A; Maruoka, Y; Gatanaga, H; Sugiyama, M; Suzuki, S; Miyo, K; Matsubara, Y; Umezawa, A; Hata, K; Kaname, T; Ozaki, K; Tokuda, H; Watanabe, H; Niida, S; Noiri, E; Kitajima, K; Omae, Y; Miyahara, R; Shimanuki, H; Kawai, Y; Tokunaga, K

PHARMACOGENOMICS JOURNAL 23 ( 6 ) 141 - 148 2023年7月（ ISSN:1470-269X eISSN:1473-1150 ）

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記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Pharmacogenomics Journal

Recently, the HLA-DQA1*05 (rs2097432) genetic variation has been reported to be linked to early infliximab (IFX) treatment failure in the Caucasian Crohn's disease (CD) population, but that evidence is scarce in the Asian population. This study aimed to investigate the relationship between rs2097432 and the cumulative discontinuation-free time of IFX (IFX persistence) in 189 Japanese biologics-naive CD patients. We also performed a genome-wide association study (GWAS) to discover novel genetic predictors for IFX persistence. The C allele of rs2097432 significantly increased the risk of early discontinuation of IFX [Hazard ratio (HR) = 2.23 and P-value = 0.026]. In GWAS, one locus tagged by rs73277969, located upstream of PPARGC1B which attenuates macrophage-mediated inflammation, reached genome-wide significance (HR = 6.04 and P-value = 7.93E-9). Pathway analysis suggested association of signaling by PDGF and FCGR activation signaling with IFX persistence (P-value = 8.56E-5 and 5.80E-4, respectively).

DOI： 10.1038/s41397-023-00312-z

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Genetic architecture of the inflammatory bowel diseases across East Asian and European ancestries 国際誌

Liu, ZJ; Liu, RZ; Gao, H; Jung, S; Gao, X; Sun, RC; Liu, XM; Kim, Y; Lee, HS; Kawai, Y; Nagasaki, M; Umeno, J; Tokunaga, K; Kinouchi, Y; Masamune, A; Shi, WZ; Shen, CG; Guo, ZL; Yuan, K; Zhu, S; Li, DL; Liu, JJ; Ge, T; Cho, J; Daly, MJ; McGovern, DPB; Ye, BD; Song, K; Kakuta, Y; Li, MS; Huang, HL; Abreu, M; Achkar, JP; Andersen, V; Bernstein, C; Brant, SR; Bujanda, L; Ng, SC; Cho, J; Daly, MJ; Denson, LA; Duerr, RH; Ferguson, LR; Franchimont, D; Franke, A; Gearry, R; Hakonarson, H; Halfvarson, J; Heller, C; Huang, HL; Julià, A; Kelsen, J; Khalili, H; Kugathasan, S; Kupcinskas, J; Latiano, A; Louis, E; Malekzadeh, R; McCauley, JL; McGovern, DPB; Moran, C; Okou, D; Orchard, T; Palotie, A; Parkes, M; Pekow, J; Potocnik, U; Radford-Smith, G; Rioux, JD; Rogler, G; Sands, B; Silverberg, M; Sokol, H; Vermeire, S; Weersma, RK; Xavier, RJ; Hu, NZ; Cao, Q; Wang, YF; Miao, YL; Zhang, HJ; Lv, XP; Gao, X; Zhang, H; Su, JL; Feng, BS; Zhao, Y; Zhu, LR; Chen, Y; Zhu, LX; Chen, CX; Wang, YL; Wang, YD; Pang, Z; Chen, YX; Zhang, XL; Li, H; Yu, Q; Ye, M; Zhang, SM; Tang, W; Wang, M; Cao, XC; Zhu, RX; Zhou, GX; Bian, ZL; Guo, XF; Wu, XL; Liu, JC; Xu, W; Li, YQ; Guo, Q; Guo, ZG; Li, MS; Liu, ZJ

NATURE GENETICS 55 ( 5 ) 796 - 806 2023年5月（ ISSN:1061-4036 eISSN:1546-1718 ）

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記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Nature Genetics

Genetic architecture of the inflammatory bowel diseases across East Asian and European ancestriesの論文がNature Geneticsに掲載された。

DOI： 10.1038/s41588-023-01384-0

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Novel HLA allele associations with susceptibility, staging, symptomatic state, autoimmune hepatitis and hepatocellular carcinoma events for primary biliary cholangitis in the Japanese population 国際誌

Khor, SS; Ueno, K; Nishida, N; Kawashima, M; Kawai, Y; Aiba, Y; Hitomi, Y; Nagasaki, M; Nakamura, M; Tokunaga, K

FRONTIERS IN IMMUNOLOGY 14 1151502 - 1151502 2023年5月（ ISSN:1664-3224 ）

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記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Frontiers in Immunology

Primary biliary cholangitis (PBC) is a rare autoimmune disease with a clear predisposition for human leukocyte antigen (HLA)-DR/DQ-associated loss of immune tolerance for the E2 component of the pyruvate dehydrogenase complex. Three-field-resolution HLA imputation of 1,670 Japanese PBC patients and 2,328 healthy controls was conducted using Japanese population-specific HLA reference panels. Eighteen previously reported Japanese PBC-associated HLA alleles were confirmed and extended to 3-field-resolution, including HLA-DRB1*08:03 to HLA-DRB1*08:03:02, HLA-DQB1*03:01 to HLA-DQB1*03:01:01, HLA-DQB1*04:01 to HLA-DQB1*04:01:01 and HLA-DQB1*06:04 to HLA-DQB1*06:04:01. In addition, additional significant novel HLA alleles were identified, including 3 novel susceptible HLA-DQA1 alleles: HLA-DQA1*03:03:01, HLA-DQA1*04:01:01, HLA-DQA1*01:04:01 and 1 novel protective HLA-DQA1 allele, HLA-DQA1*05:05:01. In addition, PBC patients carrying HLA-DRB1*15:01:01 and HLA-DQA1*03:03:01 would have a higher predisposition toward developing concomitant autoimmune hepatitis (AIH). Further, late-stage and symptomatic PBC shared the same susceptible HLA alleles of HLA-A*26:01:01, HLA-DRB1*09:01:02 and HLA-DQB1*03:03:02. Lastly, HLA-DPB1*05:01:01 was identified as a potential risk HLA allele for development of hepatocellular carcinoma (HCC) in PBC patients. In conclusion, we have extended the current knowledge of HLA allele associations to 3-field resolution and identified novel HLA allele associations with predisposition risk, staging, symptomatic state, and AIH and HCC events for Japanese PBC patients.

DOI： 10.3389/fimmu.2023.1151502

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Genome-Wide Association Study and Transcriptome of Japanese Patients with Developmental Dysplasia of the Hip Demonstrates an Association with the Ferroptosis Signaling Pathway

Mori Y., Ueno K., Chiba D., Hashimoto K., Kawai Y., Baba K., Tanaka H., Aki T., Ogasawara M., Shibasaki N., Tokunaga K., Aizawa T., Nagasaki M.

International Journal of Molecular Sciences 24 ( 5 ) 5019 - 5019 2023年3月（ ISSN:16616596 eISSN:1422-0067 ）

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記述言語：その他掲載種別：研究論文（学術雑誌）出版者・発行元：International Journal of Molecular Sciences

This study examined the association between developmental dysplasia of the hip (DDH) and disease-associated loci in a Japanese cohort. A genome-wide association study (GWAS) of 238 Japanese patients with DDH and 2044 healthy individuals was performed. As a replicate, GWAS was also conducted on the UK Biobank data with 3315 cases and matched 74,038 controls. Gene set enrichment analyses (GSEAs) of both the genetics and transcriptome of DDH were performed. Transcriptome analysis of cartilage specimens from DDH-associated osteoarthritis and femoral neck fractures was performed as a control. Most of the lead variants were very low-frequency ones in the UK, and variants in the Japanese GWAS could not be replicated with the UK GWAS. We assigned DDH-related candidate variants to 42 and 81 genes from the Japanese and UK GWASs, respectively, using functional mapping and annotation. GSEA of gene ontology, disease ontology, and canonical pathways identified the most enriched pathway to be the ferroptosis signaling pathway, both in the Japanese gene set as well as the Japanese and UK merged set. Transcriptome GSEA also identified significant downregulation of genes in the ferroptosis signaling pathway. Thus, the ferroptosis signaling pathway may be associated with the pathogenic mechanism of DDH.

DOI： 10.3390/ijms24055019

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Prediction Model with HLA-A*33:03 Reveals Number of Days to Develop Liver Cancer from Blood Test 国際誌

Nishida, N; Ohashi, J; Suda, G; Chiyoda, T; Tamaki, N; Tomiyama, T; Ogasawara, S; Sugiyama, M; Kawai, Y; Khor, SS; Nagasaki, M; Fujimoto, A; Tsuchiura, T; Ishikawa, M; Matsuda, K; Yano, H; Yoshizumi, T; Izumi, N; Hasegawa, K; Sakamoto, N; Mizokami, M; Tokunaga, K

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 24 ( 5 ) 2023年3月（ ISSN:16616596 eISSN:1422-0067 ）

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記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：International Journal of Molecular Sciences

The development of liver cancer in patients with hepatitis B is a major problem, and several models have been reported to predict the development of liver cancer. However, no predictive model involving human genetic factors has been reported to date. For the items incorporated in the prediction model reported so far, we selected items that were significant in predicting liver carcinogenesis in Japanese patients with hepatitis B and constructed a prediction model of liver carcinogenesis by the Cox proportional hazard model with the addition of Human Leukocyte Antigen (HLA) genotypes. The model, which included four items-sex, age at the time of examination, alpha-fetoprotein level (log10AFP) and presence or absence of HLA-A*33:03-revealed an area under the receiver operating characteristic curve (AUROC) of 0.862 for HCC prediction within 1 year and an AUROC of 0.863 within 3 years. A 1000 repeated validation test resulted in a C-index of 0.75 or higher, or sensitivity of 0.70 or higher, indicating that this predictive model can distinguish those at high risk of developing liver cancer within a few years with high accuracy. The prediction model constructed in this study, which can distinguish between chronic hepatitis B patients who develop hepatocellular carcinoma (HCC) early and those who develop HCC late or not, is clinically meaningful.

DOI： 10.3390/ijms24054761

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CFH-CFHR1 hybrid genes in two cases of atypical hemolytic uremic syndrome

Sugawara Y., Kato H., Nagasaki M., Yoshida Y., Fujisawa M., Minegishi N., Yamamoto M., Nangaku M.

Journal of Human Genetics 68 ( 6 ) 427 - 430 2023年2月（ ISSN:1434-5161 eISSN:1435-232X ）

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記述言語：その他掲載種別：研究論文（学術雑誌）出版者・発行元：Journal of Human Genetics

Abstract

Atypical hemolytic uremic syndrome (aHUS) is a rare complement-mediated disease that manifests as the triad of thrombotic microangiopathy. We identified two aHUS patients with neither anti-complement factor H (CFH) antibodies nor causative variants of seven aHUS-related genes (CFH, CFI, CFB, C3, MCP, THBD, and DGKE); however, their plasma showed increased levels of hemolysis by hemolytic assay, which strongly suggests CFH-related abnormalities. Using a copy number variation (CNV) analysis of the CFH/CFHR gene cluster, we identified CFH-CFHR1 hybrid genes in these patients. We verified the absence of aHUS-related abnormal CNVs of the CFH gene in control genomes of 2036 individuals in the general population, which suggests that pathogenicity is related to these hybrid genes. Our study emphasizes that, for patients suspected of having aHUS, it is important to perform an integrated analysis based on a clinical examination, functional analysis, and detailed genetic investigation.

DOI： 10.1038/s10038-023-01129-1

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その他リンク： https://www.nature.com/articles/s10038-023-01129-1
Design and implementation of a hybrid cloud system for large-scale human genomic research 査読国際誌

Masao Nagasaki, Yayoi Sekiya, Akihiro Asakura, Ryo Teraoka, Ryoko Otokozawa, Hiroki Hashimoto, Takahisa Kawaguchi, Keiichiro Fukazawa, Yuichi Inadomi, Ken T. Murata, Yasuyuki Ohkawa, Izumi Yamaguchi, Takamichi Mizuhara, Katsushi Tokunaga, Yuji Sekiya, Toshihiro Hanawa, Ryo Yamada, Fumihiko Matsuda

Human Genome Variation 10 ( 1 ) 6 - 6 2023年2月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1038/s41439-023-00231-2
Secure secondary utilization system of genomic data using quantum secure cloud

Fujiwara M., Hashimoto H., Doi K., Kujiraoka M., Tanizawa Y., Ishida Y., Sasaki M., Nagasaki M.

Scientific Reports 12 ( 1 ) 2022年12月

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出版者・発行元：Scientific Reports

Secure storage and secondary use of individual human genome data is increasingly important for genome research and personalized medicine. Currently, it is necessary to store the whole genome sequencing information (FASTQ data), which enables detections of de novo mutations and structural variations in the analysis of hereditary diseases and cancer. Furthermore, bioinformatics tools to analyze FASTQ data are frequently updated to improve the precision and recall of detected variants. However, existing secure secondary use of data, such as multi-party computation or homomorphic encryption, can handle only a limited algorithms and usually requires huge computational resources. Here, we developed a high-performance one-stop system for large-scale genome data analysis with secure secondary use of the data by the data owner and multiple users with different levels of data access control. Our quantum secure cloud system is a distributed secure genomic data analysis system (DSGD) with a “trusted server” built on a quantum secure cloud, the information-theoretically secure Tokyo QKD Network. The trusted server will be capable of deploying and running a variety of sequencing analysis hardware, such as GPUs and FPGAs, as well as CPU-based software. We demonstrated that DSGD achieved comparable throughput with and without encryption on the trusted server Therefore, our system is ready to be installed at research institutes and hospitals that make diagnoses based on whole genome sequencing on a daily basis.

DOI： 10.1038/s41598-022-22804-x

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Sex-Specific Differences in the Transcriptome of the Human Dorsolateral Prefrontal Cortex in Schizophrenia 国際誌

Yu Z., Ueno K., Funayama R., Sakai M., Nariai N., Kojima K., Kikuchi Y., Li X., Ono C., Kanatani J., Ono J., Iwamoto K., Hashimoto K., Kinoshita K., Nakayama K., Nagasaki M., Tomita H.

Molecular Neurobiology 60 ( 2 ) 1083 - 1098 2022年11月（ ISSN:08937648 ）

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記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Molecular Neurobiology

Schizophrenia presents clinical and biological differences between males and females. This study investigated transcriptional profiles in the dorsolateral prefrontal cortex (DLPFC) using postmortem data from the largest RNA-sequencing (RNA-seq) database on schizophrenic cases and controls. Data for 154 male and 113 female controls and 160 male and 93 female schizophrenic cases were obtained from the CommonMind Consortium. In the RNA-seq database, the principal component analysis showed that sex effects were small in schizophrenia. After we analyzed the impact of sex-specific differences on gene expression, the female group showed more significantly changed genes compared with the male group. Based on the gene ontology analysis, the female sex-specific genes that changed were overrepresented in the mitochondrion, ATP (phosphocreatine and adenosine triphosphate)-, and metal ion-binding relevant biological processes. An ingenuity pathway analysis revealed that the differentially expressed genes related to schizophrenia in the female group were involved in midbrain dopaminergic and γ-aminobutyric acid (GABA)-ergic neurons and microglia. We used methylated DNA-binding domain-sequencing analyses and microarray to investigate the DNA methylation that potentially impacts the sex differences in gene transcription using a maternal immune activation (MIA) murine model. Among the sex-specific positional genes related to schizophrenia in the PFC of female offspring from MIA, the changes in the methylation and transcriptional expression of loci ACSBG1 were validated in the females with schizophrenia in independent postmortem samples by real-time PCR and pyrosequencing. Our results reveal potential genetic risks in the DLPFC for the sex-dependent prevalence and symptomology of schizophrenia.

DOI： 10.1007/s12035-022-03109-6

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rs2013278 in the multiple immunological-trait susceptibility locus CD28 regulates the production of non-functional splicing isoforms 国際誌

Hitomi Y., Aiba Y., Ueno K., Nishida N., Kawai Y., Kawashima M., Tsuiji M., Iwabuchi C., Takada S., Miyake N., Nagasaki M., Tokunaga K., Nakamura M.

Human Genomics 16 ( 1 ) 46 - 46 2022年10月（ ISSN:14739542 ）

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記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Human Genomics

BACKGROUND: Ligation of CD28 with ligands such as CD80 or CD86 provides a critical second signal alongside antigen presentation by class II major histocompatibility complex expressed on antigen-presenting cells through the T cell antigen receptor for naïve T cell activation. A number of studies suggested that CD28 plays an important role in the pathogenesis of various human diseases. Recent genome-wide association studies (GWASs) identified CD28 as a susceptibility locus for lymphocyte and eosinophil counts, multiple sclerosis, ulcerative colitis, celiac disease, rheumatoid arthritis, asthma, and primary biliary cholangitis. However, the primary functional variant and molecular mechanisms of disease susceptibility in this locus remain to be elucidated. This study aimed to identify the primary functional variant from thousands of genetic variants in the CD28 locus and elucidate its functional effect on the CD28 molecule. RESULTS: Among the genetic variants exhibiting stronger linkage disequilibrium (LD) with all GWAS-lead variants in the CD28 locus, rs2013278, located in the Rbfox binding motif related to splicing regulation, was identified as a primary functional variant related to multiple immunological traits. Relative endogenous expression levels of CD28 splicing isoforms (CD28i and CD28Δex2) compared with full-length CD28 in allele knock-in cell lines generated using CRISPR/Cas9 were directly regulated by rs2013278 (P < 0.05). Although full-length CD28 protein expressed on Jurkat T cells showed higher binding affinity for CD80/CD86, both CD28i and CD28Δex2 encoded loss-of-function isoforms. CONCLUSION: The present study demonstrated for the first time that CD28 has a shared disease-related primary functional variant (i.e., rs2013278) that regulates the CD28 alternative splicing that generates loss-of-function isoforms. They reduce disease risk by inducing anergy of effector T cells that over-react to autoantigens and allergens.

DOI： 10.1186/s40246-022-00419-7

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原発性胆汁性胆管炎の肝組織におけるPOU2AF1とその関連遺伝子の解析

相葉佳洋, 伊東正博, 植野和子, 人見祐基, 小森敦正, 阿比留正剛, 長岡進矢, 八橋弘, 長崎正朗, 徳永勝士, 中村稔

日本臨床免疫学会総会プログラム・抄録集 50回 109 - 109 2022年10月

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記述言語：日本語出版者・発行元：(一社)日本臨床免疫学会

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Genome-wide Survival Analysis for Macular Neovascularization Development in Central Serous Chorioretinopathy Revealed Shared Genetic Susceptibility with Polypoidal Choroidal Vasculopathy 査読国際誌

Mori Y., Miyake M., Hosoda Y., Miki A., Takahashi A., Muraoka Y., Miyata M., Sato T., Tamura H., Ooto S., Yamada R., Yamashiro K., Nakamura M., Tajima A., Nagasaki M., Honda S., Tsujikawa A.

Ophthalmology 129 ( 9 ) 1034 - 1042 2022年9月（ ISSN:01616420 ）

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記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Ophthalmology

PURPOSE: To identify susceptibility genes for macular neovascularization (MNV) development in central serous chorioretinopathy (CSC). DESIGN: Genome-wide survival analysis using a longitudinal cohort study. PARTICIPANTS: We included 402 and 137 patients with CSC but without MNV at their first visit from the Kyoto CSC Cohort and Kobe CSC dataset, respectively. All patients underwent detailed ophthalmologic examinations, including multimodal imaging, such as fundus autofluorescence, spectral-domain optical coherence tomography, and fluorescein angiography/indocyanine green angiography and/or optimal coherence tomography angiography. METHODS: We conducted a genome-wide survival analysis using the Kyoto CSC Cohort. We applied the Cox proportional hazard model to adjust for age, sex, and the first principal component. Single nucleotide polymorphisms (SNPs) with P-values <1.0×10-5 were carried forward to the replication in the Kobe CSC dataset. Moreover, we evaluated the contribution of previously-reported age-related macular degeneration (AMD) susceptibility loci. We used FUMA and ToppFun for the functional enrichment analysis. MAIN OUTCOME MEASURES: The association between SNPs and MNV development in patients with CSC. RESULTS: Rs370974631 near ARMS2 displayed a genome-wide significant association in the meta-analysis of discovery and replication result (hazard ratio [HR]meta = 3.63; Pmeta = 5.76×10-9). Among previously-reported AMD susceptibility loci, we additionally identified CFH rs800292 (HR = 0.39, P = 2.55×10-4), COL4A3 rs4276018 (HR = 0.26, P = 1.56×10-3), and B3GALTL rs9564692 (HR = 0.56, P = 8.30×10-3) as susceptibility loci for MNV development in CSC. The functional enrichment analysis revealed significant enrichment of eight pathways (GO:0051561, GO:0036444, GO:0008282, GO:1990246, GO:0015272, GO:0030955, GO:0031420, and GO:0005242) related to ion transport. CONCLUSIONS: ARMS2, CFH, COL4A3, and B3GALTL were identified as susceptibility genes for MNV development in CSC. The aforementioned four genes are known as susceptibility genes for AMD, whereas COL4A3 and B3GALTL were previously reported to be polypoidal choroidal vasculopathy (PCV)-specific susceptibility genes. Our findings revealed the shared genetic susceptibility between PCV and MNV secondary to CSC.

DOI： 10.1016/j.ophtha.2022.04.018

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Antiemetic effects of baclofen in a shrew model of postoperative nausea and vomiting: Whole‐transcriptome analysis in the nucleus of the solitary tract 国際誌

Daisuke Konno, Shigekazu Sugino, Tomoko F Shibata, Kazuharu Misawa, Yuka Imamura‐Kawasawa, Jun Suzuki, Kanta Kido, Masao Nagasaki, Masanori Yamauchi

CNS Neuroscience and Therapeutics 28 ( 6 ) 922 - 931 2022年3月（ ISSN:17555930 ）

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記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：CNS Neuroscience and Therapeutics

AIMS: The molecular genetic mechanisms underlying postoperative nausea and vomiting (PONV) in the brain have not been fully elucidated. This study aimed to determine the changes in whole transcriptome in the nucleus of the solitary tract (NTS) in an animal model of PONV, to screen a drug candidate and to elucidate the molecular genetic mechanisms of PONV development. METHODS: Twenty-one female musk shrews were assigned into three groups: the Surgery group (shrew PONV model, n = 9), the Sham group (n = 6), and the Naïve group (n = 6). In behavioral studies, the main outcome was the number of emetic episodes. In genetic experiments, changes in the transcriptome in the NTS were measured. In a separate study, 12 shrews were used to verify the candidate mechanism underlying PONV. RESULTS: A median of six emetic episodes occurred in both the Sham and Surgery groups. Whole-transcriptome analysis indicated the inhibition of the GABAB receptor-mediated signaling pathway in the PONV model. Baclofen (GABAB receptor agonist) administration eliminated emetic behaviors in the shrew PONV model. CONCLUSIONS: Our findings suggest that the GABAB receptor-mediated signaling pathway is involved in emesis and that baclofen may be a novel therapeutic or prophylactic agent for PONV.

DOI： 10.1111/cns.13823

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A single-nucleotide-polymorphism in the 5′-flanking region of MSX1 gene as a predictive marker candidate for platinum-based therapy of esophageal carcinoma 国際誌

Mori T., Ueno K., Tokunaga K., Kawai Y., Matsuda K., Nishida N., Komine K., Saito S., Nagasaki M.

Therapeutic Advances in Medical Oncology 14 175883592210805 - 175883592210805 2022年2月（ ISSN:1758-8359 ）

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記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Therapeutic Advances in Medical Oncology

<jats:sec><jats:title>Background:</jats:title><jats:p> Platinum derivatives are important treatment options for patients with esophageal carcinoma (EC), and a predictive marker for platinum-based therapy is needed for precision medicine. </jats:p></jats:sec><jats:sec><jats:title>Patients and methods:</jats:title><jats:p> This study contained two cohorts consisting of EC patients treated using platinum-based chemoradiation therapy (CRT) as the first-line and another external cohort of nationwide clinicogenomic data from the BioBank Japan (BBJ). </jats:p></jats:sec><jats:sec><jats:title>Results:</jats:title><jats:p> Genome-wide association study (GWAS) of therapeutic outcomes, refractory disease or not, following platinum-based CRT as first-line in 94 patients in the first cohort suggested the association of 89 SNPs using p < 0.0001. The top 10 SNPs selected from each chromosomal region by odds ratio were evaluated for progression-free survival (PFS) and overall survival (OS) hazard ratios in the first cohort, resulting in four candidates ( p < 0.0025). The four selected candidates were re-evaluated in another cohort of 24 EC patients, which included patients prospectively enrolled in this study to fulfill the sample size statistically suggested by the results of the first cohort, and of the four, only rs3815544 was replicated ( p < 0.0125). Furthermore, this candidate genotype of rs3815544 proceeded to the re-evaluation study in an external cohort consisting of EC patients treated with platinum derivatives and/or by radiation therapy as the first-line treatment in BBJ, which confirmed that the alternative allele (G) of rs3815544 was statistically associated with non-response (SD or PD) to platinum-based therapy in EC patients (odds ratio = 1.801, p = 0.048). The methylation QTL database as well as online clinicogenomic databases suggested that the region including rs3815544 may regulate MSX1 expression through CpG methylation, and this down-regulation was statistically associated with poor prognosis after platinum-based therapies for EC. </jats:p></jats:sec><jats:sec><jats:title>Conclusion:</jats:title><jats:p> rs3815544 is a novel candidate predictive marker for platinum-based EC therapy. </jats:p></jats:sec>

DOI： 10.1177/17588359221080580

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Genetic Background of Mesalamine-induced Fever and Diarrhea in Japanese Patients with Inflammatory Bowel Disease

Suzuki K., Kakuta Y., Naito T., Takagawa T., Hanai H., Araki H., Sasaki Y., Sakuraba H., Sasaki M., Hisamatsu T., Motoya S., Matsumoto T., Onodera M., Ishiguro Y., Nakase H., Andoh A., Hiraoka S., Shinozaki M., Fujii T., Katsurada T., Kobayashi T., Fujiya M., Otsuka T., Oshima N., Suzuki Y., Sato Y., Hokari R., Noguchi M., Ohta Y., Matsuura M., Kawai Y., Tokunaga K., Nagasaki M., Kudo H., Minegishi N., Okamoto D., Shimoyama Y., Moroi R., Kuroha M., Shiga H., Li D., McGovern D.P.B., Kinouchi Y., Masamune A., Ikeya K., Nishida A., Nakagawa S., Miura M., Toyonaga T., Onodera K., Takahara M., Yanai S., Ishihara S., Nagahori M., Matsuoka K., Arai K., Mizuno S., Naganuma M., Nakamura S., Ishikawa T., Nakajima H., Terasaki H., Saito R., Amemiya I., Ohyama H., Korekawa K., Iwaki H., Takahashi S., Makuuchi M., Inomata Y., Shimoda F., Takahashi T., Yano K., Abe I., Handa T., Masu Y., Hishinuma K., Kanazawa Y., Kimura T., Negoro K., Kato M.

Inflammatory Bowel Diseases 28 ( 1 ) 21 - 31 2022年1月（ ISSN:10780998 ）

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出版者・発行元：Inflammatory Bowel Diseases

Background: Some patients with inflammatory bowel disease (IBD) who were under mesalamine treatment develop adverse reactions called "mesalamine allergy,"which includes high fever and worsening diarrhea. Currently, there is no method to predict mesalamine allergy. Pharmacogenomic approaches may help identify these patients. Here we analyzed the genetic background of mesalamine intolerance in the first genome-wide association study of Japanese patients with IBD. Methods: Two independent pharmacogenetic IBD cohorts were analyzed: the MENDEL (n = 1523; as a discovery set) and the Tohoku (n = 788; as a replication set) cohorts. Genome-wide association studies were performed in each population, followed by a meta-analysis. In addition, we constructed a polygenic risk score model and combined genetic and clinical factors to model mesalamine intolerance. Results: In the combined cohort, mesalamine-induced fever and/or diarrhea was significantly more frequent in ulcerative colitis vs Crohn's disease. The genome-wide association studies and meta-analysis identified one significant association between rs144384547 (upstream of RGS17) and mesalamine-induced fever and diarrhea (P = 7.21e-09; odds ratio = 11.2). The estimated heritability of mesalamine allergy was 25.4%, suggesting a significant correlation with the genetic background. Furthermore, a polygenic risk score model was built to predict mesalamine allergy (P = 2.95e-2). The combined genetic/clinical prediction model yielded a higher area under the curve than did the polygenic risk score or clinical model alone (area under the curve, 0.89; sensitivity, 71.4%; specificity, 90.8%). Conclusions: Mesalamine allergy was more common in ulcerative colitis than in Crohn's disease. We identified a novel genetic association with and developed a combined clinical/genetic model for this adverse event.

DOI： 10.1093/ibd/izab004

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rs9459874 and rs1012656 in CCR6/FGFR1OP confer susceptibility to primary biliary cholangitis 国際誌

Hitomi Y., Aiba Y., Ueno K., Nishida N., Kawai Y., Kawashima M., Yasunami M., Gervais O., Ito M., Cordell H.J., Mells G.F., Nagasaki M., Tokunaga K., Tsuiji M., Nakamura M.

Journal of Autoimmunity 126 102775 - 102775 2022年1月（ ISSN:08968411 ）

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記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Journal of Autoimmunity

Primary biliary cholangitis (PBC) is a chronic cholestatic autoimmune liver disease that appears to be strongly influenced by genetic factors. Recently, an international meta-analysis of genome-wide association studies (GWAS) identified CC-Motif Chemokine Receptor-6 (CCR6) and FGFR1 Oncogene-Partner (FGFR1OP) as PBC-susceptibility genes. However, the lead single nucleotide polymorphisms (SNPs) of CCR6/FGFR1OP showed low linkage disequilibrium with each other in East Asian and European populations. Additionally, the primary functional variants and the molecular mechanisms responsible for PBC-susceptibility remain unclear. Here, among the PBC-susceptibility SNPs identified by high-density association mapping in our previous meta-GWAS (Patients: n = 10,516; healthy controls: n = 20,772) within the CCR6/FGFR1OP locus, rs9459874 and rs1012656 were identified as primary functional variants. These functional variants accounted for the effects of GWAS-identified lead SNPs in CCR6/FGFR1OP. Additionally, the roles of rs9459874 and rs1012656 in regulating FGFR1OP transcription and CCR6 translation, respectively, were supported by expression quantitative trait loci (eQTL) analysis and gene editing technology using the CRISPR/Cas9 system. Immunohistochemistry showed higher expression of CCR6 protein in the livers of patients with PBC than in those of a non-diseased control. In conclusion, we identified primary functional variants in CCR6/FGFR1OP and revealed the molecular mechanisms by which these variants confer PBC-susceptibility in an eQTL-dependent or -independent manner. The approach in this study is applicable for the elucidation of the pathogenesis of other autoimmune disorders in which CCR6/FGFR1OP is known as a susceptibility locus, as well as PBC.

DOI： 10.1016/j.jaut.2021.102775

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Mapping of susceptible variants for cold medicine-related Stevens–Johnson syndrome by whole-genome resequencing 国際誌

6 ( 1 ) 9 - 9 2021年12月

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記述言語：英語掲載種別：研究論文（学術雑誌）

Stevens-Johnson syndrome (SJS) and its severe condition with extensive skin detachment and a poor prognosis, toxic epidermal necrolysis (TEN), are immunologically mediated severe cutaneous reactions of the skin and mucous membranes such as the ocular surface. Genetic variations on the HLA-A and other autosomal genes have been identified as risk factors for cold medicine-related SJS/TEN with severe ocular complications (CM-SJS/TEN with SOC). Using a whole-genome sequencing (WGS) approach, we explored other susceptible variants of CM-SJS/TEN with SOC, especially among rare variants and structural variants (SVs). WGS was performed on samples from 133 patients with CM-SJS/TEN with SOC and 418 healthy controls to obtain single nucleotide polymorphisms (SNPs) and SVs. Genome-wide association tests were performed with these variants. Our genome-wide association test reproduced the associations of the common variants of HLA-A and loci on chromosome 16q12.1. We also identified novel associations of SVs on these loci and an aggregation of rare coding variants on the TPRM8 gene. In silico gene expression analysis on the HLA-A locus revealed that the SNP (rs12202296), which was significantly associated with susceptibility to CM-SJS/TEN with SOC, was correlated to an increase in HLA-A expression levels in the whole blood (P = 2.9 × 10-17), from the GTEx database. The majority of variants that were significantly associated with CM-SJS/TEN with SOC were found in non-coding regions, indicating the regulatory role of genetic variations in the pathogenesis of CM-SJS/TEN with SOC.

DOI： 10.1038/s41525-021-00171-2
Crohn's Disease and Early Exposure to Thiopurines are Independent Risk Factors for Mosaic Chromosomal Alterations in Patients with Inflammatory Bowel Diseases 国際誌

Kakuta, Y; Iwaki, H; Umeno, J; Kawai, Y; Kawahara, M; Takagawa, T; Shimoyama, Y; Naito, T; Moroi, R; Kuroha, M; Shiga, H; Watanabe, K; Nakamura, S; Nakase, H; Sasaki, M; Hanai, H; Fuyuno, Y; Hirano, A; Matsumoto, T; Kudo, H; Minegishi, N; Nakamura, M; Hisamatsu, T; Andoh, A; Nagasaki, M; Tokunaga, K; Kinouchi, Y; Masamune, A

JOURNAL OF CROHNS & COLITIS 16 ( 4 ) 643 - 655 2021年11月（ ISSN:1873-9946 eISSN:1876-4479 ）

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記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Journal of Crohn's and Colitis

BACKGROUND AND AIMS: Mosaic chromosomal alterations (mCAs) increase the risk for hematopoietic malignancies and may be risk factors for several other diseases. Inflammatory bowel diseases (IBDs), including Crohn's disease (CD) and ulcerative colitis (UC), are associated with mCAs, and patients may be at risk for hematopoietic malignancy development and/or modification of IBD phenotypes. In the present study, we screened patients with IBD for the presence of mCAs and explored the possible pathophysiological and genetic risk factors for mCAs. METHODS: We analyzed mCAs in peripheral blood from 3,339 patients with IBD and investigated the clinical and genetic risk factors for mCAs. RESULTS: CD and exposure to thiopurines before the age of 20 years were identified as novel independent risk factors for mCAs (odds ratio = 2.15 and 5.68, P = 1.17e-2 and 1.60e-3, respectively). In contrast, there were no significant associations of disease duration, anti-tumor necrosis factor alpha antibodies, or other clinical factors with mCAs. Gene ontology enrichment analysis revealed that genes specifically located in the mCAs in patients with CD were significantly associated with factors related to mucosal immune responses. A genome-wide association study revealed that ERBIN, CD96, and AC068672.2 were significantly associated with mCAs in patients with CD (P = 1.56e-8, 1.65e-8, and 4.92e-8, respectively). CONCLUSION: The difference in mCAs between patients with CD and UC supports the higher incidence of hematopoietic malignancies in CD. Caution should be exercised when using thiopurines in young patients with IBD, particularly CD, in light of possible chromosomal alterations.

DOI： 10.1093/ecco-jcc/jjab199

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Machine learning approaches to predict gestational age in normal and complicated pregnancies via urinary metabolomics analysis. 国際誌

Takafumi Yamauchi, Daisuke Ochi, Naomi Matsukawa, Daisuke Saigusa, Mami Ishikuro, Taku Obara, Yoshiki Tsunemoto, Satsuki Kumatani, Riu Yamashita, Osamu Tanabe, Naoko Minegishi, Seizo Koshiba, Hirohito Metoki, Shinichi Kuriyama, Nobuo Yaegashi, Masayuki Yamamoto, Masao Nagasaki, Satoshi Hiyama, Junichi Sugawara

Scientific reports 11 ( 1 ) 17777 - 17777 2021年9月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1038/s41598-021-97342-z
まれな変異に重点を置いた尿酸値の遺伝率の研究

三澤計治, 三島英換, 長谷川嵩矩, 大内基司, 小島要, 河合洋介, 松尾雅文, 安西尚彦, 長崎正朗

痛風と尿酸・核酸 45 ( 1 ) 23 - 30 2021年7月

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記述言語：日本語

痛風は,尿酸が原因で起こる関節炎であり,罹患者も多い.先行研究では血清尿酸値の遺伝率は30～70%と推定されている.遺伝子ベース検定を用いた最近の研究では,まれな変異の有無がヒト集団中の血清尿酸値分散に大きく寄与していることが示唆されている.遺伝子ベース検定は,1つの遺伝子に含まれる複数の遺伝子変異の影響を1回の検定で考慮するものである.本論文では,数値計算を用い,遺伝子ベース検定のサンプルサイズと検出力の関係を解析した.仮想的なヒト集団を,まれな変異を持つ人々と持たない人々の二つの群に分けた.この二群間での尿酸値の平均値の差は,先行研究によるURAT1変異の有無によって生じる差と同じ値を使った.また,各個人の尿酸値は,その個人が属する各群の平均値を期待値とする正規分布に従うと仮定した.等分散性を仮定しないWelchのt検定を行い,検出力を計算した.今回の数値計算から,まれな変異は,一つのSNPだけを用いている場合,1万人から数万人ほどの大きさのサンプルが必要であることがわかった.複数のSNPをまとめた検定を行うことで,検出力が上がり,数百から数千人規模の研究でも検出できることが示された.この研究は,今まで主に研究対象となってきた「ありふれた疾患,ありふれた変異」に加え,遺伝子ベース検定による,「ありふれた疾患,まれな変異」の研究の可能性を示した.(著者抄録)
X Chromosome Contribution to the Genetic Architecture of Primary Biliary Cholangitis. 国際誌

Rosanna Asselta, Elvezia M Paraboschi, Alessio Gerussi, Heather J Cordell, George F Mells, Richard N Sandford, David E Jones, Minoru Nakamura, Kazuko Ueno, Yuki Hitomi, Minae Kawashima, Nao Nishida, Katsushi Tokunaga, Masao Nagasaki, Atsushi Tanaka, Ruqi Tang, Zhiqiang Li, Yongyong Shi, Xiangdong Liu, Ma Xiong, Gideon Hirschfield, Katherine A Siminovitch, Marco Carbone, Giulia Cardamone, Stefano Duga, M Eric Gershwin, Michael F Seldin, Pietro Invernizzi

Gastroenterology 160 ( 7 ) 2483 - 2495 2021年6月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1053/j.gastro.2021.02.061
An international genome-wide meta-analysis of primary biliary cholangitis: novel risk loci and candidate drugs 国際誌

Heather J. Cordell, James J. Fryett, Kazuko Ueno, Rebecca Darlay, Yoshihiro Aiba, Yuki Hitomi, Minae Kawashima, Nao Nishida, Seik-Soon Khor, Olivier Gervais, Yosuke Kawai, Masao Nagasaki, Katsushi Tokunaga, Ruqi Tang, Yongyong Shi, Zhiqiang Li, Brian D. Juran, Elizabeth J. Atkinson, Alessio Gerussi, Marco Carbone, Rosanna Asselta, Angela Cheung, Mariza de Andrade, Aris Baras, Julie Horowitz, Manuel A.R. Ferreira, Dylan Sun, David E. Jones, Steven Flack, Ann Spicer, Victoria L. Mulcahy, Jinyoung Byan, Younghun Han, Richard N. S, ford, Konstantinos N. Lazaridis, Christopher I. Amos, Gideon M. Hirschfield, Michael F. Seldin, Pietro Invernizzi, Katherine A. Siminovitch, Xiong Ma, Minoru Nakamura, George F. Mells, Katherine A. Siminovitch, Gideon M. Hirschfield, Andrew Mason, Catherine Vincent, Gang Xie, Jinyi Zhang, Ruqi Tang, Xiong Ma, Zhiqiang Li, Yongyong Shi, Andrea Affronti, Piero L. Almasio, Domenico Alvaro, Pietro Andreone, Angelo Andriulli, Francesco Azzaroli, Pier Maria Battezzati, Antonio Benedetti, MariaConsiglia Bragazzi, Maurizia Brunetto, Savino Bruno, Vincenza Calvaruso, Vincenzo Cardinale, Giovanni Casella, Nora Cazzagon, Antonio Ciaccio, Barbara Coco, Agostino Colli, Guido Colloredo, Massimo Colombo, Silvia Colombo, Laura Cristoferi, Carmela Cursaro, Lory Saveria Croc{`{e } }, Andrea Crosignani, Daphne D'Amato, Francesca Donato, Gianfranco Elia, Stefano Fagiuoli, Carlo Ferrari, Annarosa Floreani, Andrea Galli, Edoardo Giannini, Ignazio Grattagliano, Pietro Lampertico, Ana Lleo, Federica Malinverno, Clara Mancuso, Fabio Marra, Marco Marzioni, Sara Massironi, Alberto Mattalia, Luca Miele, Chiara Milani, Lorenzo Morini, Filomena Morisco, Luigi Muratori, Paolo Muratori, Grazia A. Niro, Sarah O'Donnell, Antonio Picciotto, Piero Portincasa, Cristina Rigamonti, Vincenzo Ronca, Floriano Rosina, Giancarlo Spinzi, Mario Strazzabosco, Mirko Tarocchi, Claudio Tiribelli, Pierluigi Toniutto, Luca Valenti, Maria Vinci, Massimo Zuin, Hitomi Nakamura, Seigo Abiru, Shinya Nagaoka, Atsumasa Komori, Hiroshi Yatsuhashi, Hiromi Ishibashi, Masahiro Ito, Kiyoshi Migita, Hiromasa Ohira, Shinji Katsushima, Atsushi Naganuma, Kazuhiro Sugi, Tatsuji Komatsu, Tomohiko Mannami, Kouki Matsushita, Kaname Yoshizawa, Fujio Makita, Toshiki Nikami, Hideo Nishimura, Hiroshi Kouno, Hirotaka Kouno, Hajime Ota, Takuya Komura, Yoko Nakamura, Masaaki Shimada, Noboru Hirashima, Toshiki Komeda, Keisuke Ario, Makoto Nakamuta, Tsutomu Yamashita, Kiyoshi Furuta, Masahiro Kikuchi, Noriaki Naeshiro, Hironao Takahashi, Yutaka Mano, Seiji Tsunematsu, Iwao Yabuuchi, Yusuke Shimada, Kazuhiko Yamauchi, Rie Sugimoto, Hironori Sakai, Eiji Mita, Masaharu Koda, Satoru Tsuruta, Hiroshi Kamitsukasa, Takeaki Sato, Naohiko Masaki, Tatsuro Kobata, Nobuyoshi Fukushima, Yukio Ohara, Toyokichi Muro, Eiichi Takesaki, Hitoshi Takaki, Tetsuo Yamamoto, Michio Kato, Yuko Nagaoki, Shigeki Hayashi, Jinya Ishida, Yukio Watanabe, Masakazu Kobayashi, Michiaki Koga, Takeo Saoshiro, Michiyasu Yagura, Keisuke Hirata, Atsushu Tanaka, Hajime Takikawa, Mikio Zeniya, Masanori Abe, Morikazu Onji, Shuichi Kaneko, Masao Honda, Kuniaki Arai, Teruko Arinaga-Hino, Etsuko Hashimoto, Makiko Taniai, Takeji Umemura, Satoru Joshita, Kazuhiko Nakao, Tatsuki Ichikawa, Hidetaka Shibata, Satoshi Yamagiwa, Masataka Seike, Koichi Honda, Shotaro Sakisaka, Yasuaki Takeyama, Masaru Harada, Michio Senju, Osamu Yokosuka, Tatsuo K, a, Yoshiyuki Ueno, Kentaro Kikuchi, Hirotoshi Ebinuma, Takashi Himoto, Michio Yasunami, Kazumoto Murata, Masashi Mizokami, Kazuhito Kawata, Shinji Shimoda, Yasuhiro Miyake, Akinobu Takaki, Kazuhide Yamamoto, Katsuji Hirano, Takafumi Ichida, Akio Ido, Hirohito Tsubouchi, Kazuaki Chayama, Kenichi Harada, Yasuni Nakanuma, Yoshihiko Maehara, Akinobu Taketomi, Ken Shirabe, Yuji Soejima, Akira Mori, Shintaro Yagi, Shinji Uemoto, H. Egawa, Tomohiro Tanaka, Noriyo Yamashiki, Sumito Tamura, Yasuhiro Sugawara, Norihiro Kokudo, Richard Sturgess, Christopher Healey, Andrew Yeoman, Anton VJ. Gunasekera, Paul Kooner, Kapil Kapur, V. Sathyanarayana, Yiannis Kallis, Javaid Subhani, Rory Harvey, Roger McCorry, Paul Rooney, David Ramanaden, Richard Evans, Thiriloganathan Mathialahan, Jaber Gasem, Christopher Shorrock, Mahesh Bhalme, Paul Southern, Jeremy A. Tibble, David A. Gorard, Susan Jones, George Mells, Victoria Mulcahy, Brijesh Srivastava, Matthew R. Foxton, Carole E. Collins, David Elphick, Mazn Karmo, Francisco Porras-Perez, Michael Mendall, Tom Yapp, Minesh Patel, Rol, Ede, Joanne Sayer, James Jupp, Neil Fisher, Martyn J. Carter, Konrad Koss, Jayshri Shah, Andrzej Piotrowicz, Glyn Scott, Charles Grimley, Ian R. Gooding, Simon Williams, Judith Tidbury, Guan Lim, Kuldeep Cheent, Sass Levi, Dina Mansour, Matilda Beckley, Coral Hollywood, Terry Wong, Richard Marley, John Ramage, Harriet M. Gordon, Jo Ridpath, Theodore Ngatchu, Vijay Paul Bob Grover, Ray G. Shidrawi, George Abouda, L. Corless, Mark Narain, Ian Rees, Ashley Brown, Simon Taylor-Robinson, Joy Wilkins, Leonie Grellier, Paul Banim, Debasish Das, Michael A. Heneghan, Howard Curtis, Helen C. Matthews, Faiyaz Mohammed, Mark Aldersley, Raj Srirajaskanthan, Giles Walker, Alistair McNair, Amar Sharif, Sambit Sen, George Bird, Martin I. Prince, Geeta Prasad, Paul Kitchen, Adrian Barnardo, Chirag Oza, Nurani N. Sivaramakrishnan, Prakash Gupta, Amir Shah, Chris DJ. Evans, Subrata Saha, Katharine Pollock, Peter Bramley, Ashis Mukhopadhya, Stephen T. Barclay, Natasha McDonald, Andrew J. Bathgate, Kelvin Palmer, John F. Dillon, Simon M. Rushbrook, Robert Przemioslo, Chris McDonald, Andrew Millar, Cheh Tai, Stephen Mitchell, Jane Metcalf, Syed Shaukat, Mary Ninkovic, Udi Shmueli, Andrew Davis, Asifabbas Naqvi, Tom JW. Lee, Stephen Ryder, Jane Collier, Howard Klass, Matthew E. Cramp, Nichols Sharer, Richard Aspinall, Deb Ghosh, Andrew C. Douds, Jonathan Booth, Earl Williams, Hyder Hussaini, John Christie, Steven Mann, Douglas Thorburn, Aileen Marshall, Imran Patanwala, Aftab Ala, Julia Maltby, Ray Matthew, Chris Corbett, Sam Vyas, Saket Singhal, Dermot Gleeson, Sharat Misra, Jeff Butterworth, Keith George, Tim Harding, Andrew Douglass, Harriet Mitchison, Simon Panter, Jeremy Shearman, Gary Bray, Michael Roberts, Graham Butcher, Daniel Forton, Zahid Mahmood, Matthew Cowan, Debashis Das, Chin Lye Ch{ extquotesingle}ng, Mesbah Rahman, Gregory C.A. Whatley, Emma Wesley, Aditya M, al, Sanjiv Jain, Stephen P. Pereira, Mark Wright, Palak Trivedi, Fiona H. Gordon, Esther Unitt, Altaf Palejwala, Andrew Austin, Vishwaraj Vemala, Allister Grant, Andrew D. Higham, Alison Brind, Ray Mathew, Mark Cox, Subramaniam Ramakrishnan, Alistair King, Simon Whalley, Jocelyn Fraser, S.J. Thomson, Andrew Bell, Voi Shim Wong, Richard Kia, Ian Gee, Richard Keld, Rupert Ransford, James Gotto, Charles Millson, Brian D. Juran, Elizabeth J. Atkinson, Angela Cheung, Mariza de Andrade, Konstantinos N. Lazaridis, Naga Chalasani, Vel Luketic, Joseph Odin, Kapil Chopra, Aris Baras, Julie Horowitz, Goncalo Abecasis, Michael Cantor, Giovanni Coppola, Aris Economides, Luca A. Lotta, John D. Overton, Jeffrey G. Reid, Alan Shuldiner, Christina Beechert, Caitlin Forsythe, Erin D. Fuller, Zhenhua Gu, Michael Lattari, Alex, er Lopez, John D. Overton, Thomas D. Schleicher, Maria Sotiropoulos Padilla, Karina Toledo, Louis Widom, Sarah E. Wolf, Manasi Pradhan, Kia Manoochehri, Ricardo H. Ulloa, Xiaodong Bai, Suganthi Balasubramanian, Lel, Barnard, Andrew Blumenfeld, Gisu Eom, Lukas Habegger, Alicia Hawes, Shareef Khalid, Jeffrey G. Reid, Evan K. Maxwell, William Salerno, Jeffrey C. Staples, Marcus B. Jones, Lyndon J. Mitnaul

Journal of Hepatology 75 ( 3 ) 572 - 581 2021年5月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1016/j.jhep.2021.04.055
Regional heritability mapping identifies several novel loci (STAT4, ULK4, and KCNH5) for primary biliary cholangitis in the Japanese population 国際誌

Olivier Gervais, Kazuko Ueno, Yosuke Kawai, Yuki Hitomi, Yoshihiro Aiba, Mayumi Ueta, Minoru Nakamura, Katsushi Tokunaga, Masao Nagasaki

European Journal of Human Genetics 29 ( 8 ) 1282 - 1291 2021年4月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1038/s41431-021-00854-5
High-speed parameter search of dynamic biological pathways from time-course transcriptomic profiles using high-level Petri net

Chen Li, Jiale Qin, Keisuke Kuroyanagi, Lu Lu, Masao Nagasaki, Miyano Satoru

Biosystems 201 104332 - 104332 2021年3月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1016/j.biosystems.2020.104332
rs1944919 on chromosome 11q23.1 and its effector genes COLCA1/COLCA2 confer susceptibility to primary biliary cholangitis. 国際誌

Yuki Hitomi, Yoshihiro Aiba, Yosuke Kawai, Kaname Kojima, Kazuko Ueno, Nao Nishida, Minae Kawashima, Olivier Gervais, Seik-Soon Khor, Masao Nagasaki, Katsushi Tokunaga, Minoru Nakamura, Makoto Tsuiji

Scientific reports 11 ( 1 ) 4557 - 4557 2021年2月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1038/s41598-021-84042-x
Practical guide for managing large-scale human genome data in research

Tomoya Tanjo, Yosuke Kawai, Katsushi Tokunaga, Osamu Ogasawara, Masao Nagasaki

Journal of Human Genetics 66 ( 1 ) 39 - 52 2021年1月

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記述言語：その他掲載種別：研究論文（学術雑誌）

DOI： 10.1038/s10038-020-00862-1
Long non-coding RNA MIR4300HG polymorphisms are associated with postoperative nausea and vomiting: a genome-wide association study 査読

Masao Nagasaki

Human Genomics 14 ( 1 ) 2020年12月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1186/s40246-020-00282-4
Direct reprogramming of human umbilical vein- and peripheral blood-derived endothelial cells into hepatic progenitor cells

Hiroki Inada, Miyako Udono, Kanae Matsuda-Ito, Kenichi Horisawa, Yasuyuki Ohkawa, Shizuka Miura, Takeshi Goya, Junpei Yamamoto, Masao Nagasaki, Kazuko Ueno, Daisuke Saitou, Mikita Suyama, Yoshihiko Maehara, Wataru Kumamaru, Yoshihiro Ogawa, Sayaka Sekiya, Atsushi Suzuki

Nature Communications 11 ( 1 ) 2020年12月

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記述言語：その他掲載種別：研究論文（学術雑誌）

DOI： 10.1038/s41467-020-19041-z
Digenic mutations in ALDH2 and ADH5 impair formaldehyde clearance and cause a multisystem disorder, AMeD syndrome.

Masao Nagasaki

Science advances 6 ( 51 ) eabd7197 - eabd7197 2020年12月

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記述言語：その他掲載種別：研究論文（学術雑誌）

DOI： 10.1126/sciadv.abd7197
A multi-ethnic meta-analysis identifies novel genes, including ACSL5, associated with amyotrophic lateral sclerosis 査読

Masao Nagasaki

Communications Biology 3 ( 1 ) 2020年12月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1038/s42003-020-01251-2
Identification of the Novel Variants in Patients With Chronic Thromboembolic Pulmonary Hypertension. 国際誌

Nobuhiro Yaoita, Kimio Satoh, Taijyu Satoh, Toru Shimizu, Sakae Saito, Koichiro Sugimura, Shunsuke Tatebe, Saori Yamamoto, Tatsuo Aoki, Nobuhiro Kikuchi, Ryo Kurosawa, Satoshi Miyata, Masao Nagasaki, Jun Yasuda, Hiroaki Shimokawa

Journal of the American Heart Association 9 ( 21 ) e015902 2020年11月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1161/JAHA.120.015902
Genome‐Wide Association Study of Lean Nonalcoholic Fatty Liver Disease Suggests Human Leukocyte Antigen as a Novel Candidate Locus 査読国際誌

4 ( 8 ) 1124 - 1135 2020年8月

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記述言語：英語掲載種別：研究論文（学術雑誌）

Nonalcoholic fatty liver disease (NAFLD) is supposed to manifest its metabolic phenotype in the liver, but it is common to have lean individuals diagnosed with NAFLD, known as lean NAFLD. We conducted a two-stage analysis to identify NAFLD-associated loci in Japanese patients. In stage I, 275 metabolically healthy normal-weight patients with NAFLD were compared with 1,411 non-NAFLD controls adjusted for age, sex, and alcohol consumption by a genome-wide association study (GWAS). In stage II, human leukocyte antigen (HLA) in chromosome 6 (chr6) (P = 6.73E-08), microRNA (MIR) MIR548F3 in chr7 (P = 4.25E-07), myosin light chain 2 (MYL2) in chr12 (P = 4.39E-07), and glycoprotein precursor (GPC)6 in chr13 (P = 5.43E-07), as suggested by the GWAS, were assessed by single nucleotide polymorphism (SNP) association analysis of whole NAFLD against non-NAFLD in 9,726 members of the general population. A minor allele of the secondary lead SNP in chr6, rs2076529, was significantly associated (odds ratio [OR], 1.19; 95% confidence interval [CI], 1.11-1.28; P = 2.10E-06) and the lead SNP in chr7 was weakly associated (OR 1.15; 95% CI, 1.04-1.27; P = 6.19E-03) with increased NAFLD risk. Imputation-based typing of HLA showed a significant difference in the distribution of HLA-B, HLA-DR-beta chain 1 (DRB1), and HLA-DQ-beta chain 1 (DQB1) alleles in lean NAFLD GWAS. Next-generation sequence-based typing of HLA in 5,649 members of the general population replicated the significant difference of HLA-B allele distribution and the significant increase of the HLA-B*54:01 allele in whole NAFLD. Fecal metagenomic analysis of 3,420 members of the general population showed significant dissimilarity in beta-diversity analysis of rs2076529 and HLA-B*54:01 allele carriers from noncarriers. Veillonellaceae was increased but Verrucomicrobia was decreased in rs2076529 minor allele and HLA-B*54:01 allele carriers as in NAFLD. Conclusion: HLA was identified as a novel locus associated with NAFLD susceptibility, which might be affected by the alteration of gut microbiota.

DOI： 10.1002/hep4.1529
The Dynamics of Transcriptional Activation by Hepatic Reprogramming Factors 国際誌

Kenichi Horisawa, Miyako Udono, Kazuko Ueno, Yasuyuki Ohkawa, Masao Nagasaki, Sayaka Sekiya, Atsushi Suzuki

Molecular Cell 79 ( 4 ) 660 - 676.e8 2020年8月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1016/j.molcel.2020.07.012
尿酸値の失われた遺伝率は、レアバリアントがかなりの部分を説明する

三澤計治, 長谷川嵩矩, 三島英換, Jutabha Promsuk, 大内基司, 小島要, 河合洋介, 長崎正朗, 安西尚彦

痛風と尿酸・核酸 44 ( 1 ) 86 - 86 2020年7月

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記述言語：日本語
肥満と肥満にかかわる環境要因を考慮し日本人集団における17形質のゲノム遺伝率および相関査読国際誌

Olivier Gervais, 植野和子, 河合洋介, 人見祐基, 三澤計治, 寺口俊介, Yen-Yen Wang, 徳永勝士, 長﨑正朗

10 ( 7 ) 2221 - 2228 2020年7月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1534/g3.120.401242
尿酸値の失われた遺伝率は、レアバリアントがかなりの部分を説明する

三澤計治, 長谷川嵩矩, 三島英換, Jutabha Promsuk, 大内基司, 小島要, 河合洋介, 長崎正朗, 安西尚彦

痛風と尿酸・核酸 44 ( 1 ) 86 - 86 2020年7月

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記述言語：日本語
An Integrated Genomic and Transcriptomic Analysis Reveals Candidates of Susceptibility Genes for Crohn's Disease in Japanese Populations. 査読国際誌

Yoichi Kakuta, Ryo Ichikawa, Yuta Fuyuno, Atsushi Hirano, Junji Umeno, Takehiro Torisu, Kazuhiro Watanabe, Akihiro Asakura, Takeru Nakano, Yasuhiro Izumiyama, Daisuke Okamoto, Takeo Naito, Rintaro Moroi, Masatake Kuroha, Yoshitake Kanazawa, Tomoya Kimura, Hisashi Shiga, Takeshi Naito, Motohiro Esaki, Yosuke Kawai, Katsushi Tokunaga, Minoru Nakamura, Takayuki Matsumoto, Masao Nagasaki, Yoshitaka Kinouchi, Michiaki Unno, Atsushi Masamune

Scientific reports 10 ( 1 ) 10236 - 10236 2020年6月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1038/s41598-020-66951-5
Prevalence of disease-causing genes in Japanese patients with BRCA1/2-wildtype hereditary breast and ovarian cancer syndrome. 査読国際誌

Tomoko Kaneyasu, Seiichi Mori, Hideko Yamauchi, Shozo Ohsumi, Shinji Ohno, Daisuke Aoki, Shinichi Baba, Junko Kawano, Yoshio Miki, Naomichi Matsumoto, Masao Nagasaki, Reiko Yoshida, Sadako Akashi-Tanaka, Takuji Iwase, Dai Kitagawa, Kenta Masuda, Akira Hirasawa, Masami Arai, Junko Takei, Yoshimi Ide, Osamu Gotoh, Noriko Yaguchi, Mitsuyo Nishi, Keika Kaneko, Yumi Matsuyama, Megumi Okawa, Misato Suzuki, Aya Nezu, Shiro Yokoyama, Sayuri Amino, Mayuko Inuzuka, Tetsuo Noda, Seigo Nakamura

NPJ breast cancer 6 25 - 25 2020年6月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1038/s41523-020-0163-1
Common risk variants in NPHS1 and TNFSF15 are associated with childhood steroid-sensitive nephrotic syndrome 査読国際誌

Masao Nagasaki

Kidney International 98 ( 5 ) 1308 - 1322 2020年6月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1016/j.kint.2020.05.029
Variants That Affect Function of Calcium Channel TRPV6 Are Associated With Early-Onset Chronic Pancreatitis. 査読国際誌

Gastroenterology 158 ( 6 ) 1626 - 1641 2020年5月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1053/j.gastro.2020.01.005
Integrated GWAS and mRNA Microarray Analysis Identified IFNG and CD40L as the Central Upstream Regulators in Primary Biliary Cholangitis. 査読国際誌

Kazuko Ueno, Yoshihiro Aiba, Yuki Hitomi, Shinji Shimoda, Hitomi Nakamura, Olivier Gervais, Yosuke Kawai, Minae Kawashima, Nao Nishida, Seik-Soon Kohn, Kaname Kojima, Shinji Katsushima, Atsushi Naganuma, Kazuhiro Sugi, Tatsuji Komatsu, Tomohiko Mannami, Kouki Matsushita, Kaname Yoshizawa, Fujio Makita, Toshiki Nikami, Hideo Nishimura, Hiroshi Kouno, Hirotaka Kouno, Hajime Ohta, Takuya Komura, Satoru Tsuruta, Kazuhiko Yamauchi, Tatsuro Kobata, Amane Kitasato, Tamotsu Kuroki, Seigo Abiru, Shinya Nagaoka, Atsumasa Komori, Hiroshi Yatsuhashi, Kiyoshi Migita, Hiromasa Ohira, Atsushi Tanaka, Hajime Takikawa, Masao Nagasaki, Katsushi Tokunaga, Minoru Nakamura

Hepatology communications 4 ( 5 ) 724 - 738 2020年5月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1002/hep4.1497
Longitudinal plasma amino acid profiling with maternal genomic background throughout human pregnancy 査読国際誌

Matsuyuki Shirota, Daisuke Saigusa, Riu Yamashita, Yasutake Kato, Mitsuyo Matsumoto, Junya Yamagishi, Noriko Ishida, Kazuki Kumada, Yuji Oe, Hisaaki Kudo, Junji Yokozawa, Yoko Kuroki, Ikuko Motoike, Fumiki Katsuoka, Masao Nagasaki, Seizo Koshiba, Keiko Nakayama, Osamu Tanabe, Jun Yasuda, Shigeo Kure, Kengo Kinoshita, Hirohito Metoki, Shinichi Kuriyama, Nobuo Yaegashi, Masayuki Yamamoto, Junichi Sugawara

Medical Mass Spectrometry 4 ( 1 ) 36 - 49 2020年4月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.24508/mms.2020.06.001
Cohort Profile: Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study (TMM BirThree Cohort Study): rationale, progress and perspective. 査読国際誌

Shinichi Kuriyama, Hirohito Metoki, Masahiro Kikuya, Taku Obara, Mami Ishikuro, Chizuru Yamanaka, Masato Nagai, Hiroko Matsubara, Tomoko Kobayashi, Junichi Sugawara, Gen Tamiya, Atsushi Hozawa, Naoki Nakaya, Naho Tsuchiya, Tomohiro Nakamura, Akira Narita, Mana Kogure, Takumi Hirata, Ichiro Tsuji, Fuji Nagami, Nobuo Fuse, Tomohiko Arai, Yoshio Kawaguchi, Shinichi Higuchi, Masaki Sakaida, Yoichi Suzuki, Noriko Osumi, Keiko Nakayama, Kiyoshi Ito, Shinichi Egawa, Koichi Chida, Eiichi Kodama, Hideyasu Kiyomoto, Tadashi Ishii, Akito Tsuboi, Hiroaki Tomita, Yasuyuki Taki, Hiroshi Kawame, Kichiya Suzuki, Naoto Ishii, Soichi Ogishima, Satoshi Mizuno, Takako Takai-Igarashi, Naoko Minegishi, Jun Yasuda, Kazuhiko Igarashi, Ritsuko Shimizu, Masao Nagasaki, Osamu Tanabe, Seizo Koshiba, Hiroaki Hashizume, Hozumi Motohashi, Teiji Tominaga, Sadayoshi Ito, Kozo Tanno, Kiyomi Sakata, Atsushi Shimizu, Jiro Hitomi, Makoto Sasaki, Kengo Kinoshita, Hiroshi Tanaka, Tadao Kobayashi, Shigeo Kure, Nobuo Yaegashi, Masayuki Yamamoto

International journal of epidemiology 49 ( 1 ) 18 - 19 2020年2月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1093/ije/dyz169
Genetic Analysis of Ulcerative Colitis in Japanese Individuals Using Population-specific SNP Array. 査読国際誌

Daisuke Okamoto, Yosuke Kawai, Yoichi Kakuta, Takeo Naito, Takehiro Torisu, Atsushi Hirano, Junji Umeno, Yuta Fuyuno, Dalin Li, Takeru Nakano, Yasuhiro Izumiyama, Ryo Ichikawa, Keiichiro Hiramoto, Rintaro Moroi, Masatake Kuroha, Yoshitake Kanazawa, Hisashi Shiga, Katsushi Tokunaga, Minoru Nakamura, Motohiro Esaki, Takayuki Matsumoto, Dermot P B McGovern, Masao Nagasaki, Yoshitaka Kinouchi, Atsushi Masamune

Inflammatory bowel diseases 26 ( 8 ) 1177 - 1187 2020年2月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1093/ibd/izaa033
Exploring the Novel Susceptibility Gene Variants for Primary Open-Angle Glaucoma in East Asian Cohorts: The GLAU-GENDISK Study. 査読

Kim YW, Kim YJ, Cheong HS, Shiga Y, Hashimoto K, Song YJ, Kim SH, Choi HJ, Nishiguchi KM, Kawai Y, Nagasaki M, Nakazawa T, Park KH, Kim DM, Jeoung JW

Scientific reports 10 ( 1 ) 221 2020年1月

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記述言語：その他

Exploring the Novel Susceptibility Gene Variants for Primary Open-Angle Glaucoma in East Asian Cohorts: The GLAU-GENDISK Study.

DOI： 10.1038/s41598-019-57066-7
尿酸値の失われた遺伝率は、レアバリアントがかなりの部分を説明する

三澤計治, 長谷川嵩矩, 三島英換, Jutabha Promsuk, 大内基司, 小島要, 河合洋介, 長崎正朗, 安西尚彦

日本痛風・核酸代謝学会総会プログラム抄録集 53回 66 - 66 2020年1月

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記述言語：日本語
Study profile of The Tohoku Medical Megabank Community-Based Cohort Study. 査読

Atsushi Hozawa, Kozo Tanno, Naoki Nakaya, Tomohiro Nakamura, Naho Tsuchiya, Takumi Hirata, Akira Narita, Mana Kogure, Kotaro Nochioka, Ryohei Sasaki, Nobuyuki Takanashi, Kotaro Otsuka, Kiyomi Sakata, Shinichi Kuriyama, Masahiro Kikuya, Osamu Tanabe, Junichi Sugawara, Kichiya Suzuki, Yoichi Suzuki, Eiichi N Kodama, Nobuo Fuse, Hideyasu Kiyomoto, Hiroaki Tomita, Akira Uruno, Yohei Hamanaka, Hirohito Metoki, Mami Ishikuro, Taku Obara, Tomoko Kobayashi, Kazuyuki Kitatani, Takako Takai-Igarashi, Soichi Ogishima, Mamoru Satoh, Hideki Ohmomo, Akito Tsuboi, Shinichi Egawa, Tadashi Ishii, Kiyoshi Ito, Sadayoshi Ito, Yasuyuki Taki, Naoko Minegishi, Naoto Ishii, Masao Nagasaki, Kazuhiko Igarashi, Seizo Koshiba, Ritsuko Shimizu, Gen Tamiya, Keiko Nakayama, Hozumi Motohashi, Jun Yasuda, Atsushi Shimizu, Tsuyoshi Hachiya, Yuh Shiwa, Teiji Tominaga, Hiroshi Tanaka, Kotaro Oyama, Ryoichi Tanaka, Hiroshi Kawame, Akimune Fukushima, Yasushi Ishigaki, Tomoharu Tokutomi, Noriko Osumi, Tadao Kobayashi, Fuji Nagami, Hiroaki Hashizume, Tomohiro Arai, Yoshio Kawaguchi, Shinichi Higuchi, Masaki Sakaida, Ryujin Endo, Satoshi Nishizuka, Ichiro Tsuji, Jiro Hitomi, Motoyuki Nakamura, Kuniaki Ogasawara, Nobuo Yaegashi, Kengo Kinoshita, Shigeo Kure, Akio Sakai, Seiichiro Kobayashi, Kenji Sobue, Makoto Sasaki, Masayuki Yamamoto

Journal of epidemiology 31 ( 1 ) 65 - 76 2020年1月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.2188/jea.JE20190271
A low-frequency IL4R locus variant in Japanese patients with intravenous immunoglobulin therapy-unresponsive Kawasaki disease 査読

Yuji Amano, Yohei Akazawa, Jun Yasuda, Kazuhisa Yoshino, Katsuhiko Kojima, Norimoto Kobayashi, Satoshi Matsuzaki, Masao Nagasaki, Yosuke Kawai, Naoko Minegishi, Noriko Ishida, Noriko Motoki, Akira Hachiya, Yozo Nakazawa, Masayuki Yamamoto, Kenichi Koike, Toshikazu Takeshita

Pediatric Rheumatology 17 ( 1 ) 34 2019年12月

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記述言語：その他掲載種別：研究論文（学術雑誌）

DOI： 10.1186/s12969-019-0337-2
Construction of JRG (Japanese reference genome) with single-molecule real-time sequencing

Masao Nagasaki, Yoko Kuroki, Tomoko F. Shibata, Fumiki Katsuoka, Takahiro Mimori, Yosuke Kawai, Naoko Minegishi, Atsushi Hozawa, Shinichi Kuriyama, Yoichi Suzuki, Hiroshi Kawame, Fuji Nagami, Takako Takai-Igarashi, Soichi Ogishima, Kaname Kojima, Kazuharu Misawa, Osamu Tanabe, Nobuo Fuse, Hiroshi Tanaka, Nobuo Yaegashi, Kengo Kinoshita, Shiego Kure, Jun Yasuda, Masayuki Yamamoto

Human Genome Variation 6 2019年12月

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記述言語：英語掲載種別：研究論文（学術雑誌）

Construction of JRG (Japanese reference genome) with single-molecule real-time sequencing
© 2019, The Author(s). In recent genome analyses, population-specific reference panels have indicated important. However, reference panels based on short-read sequencing data do not sufficiently cover long insertions. Therefore, the nature of long insertions has not been well documented. Here, we assembled a Japanese genome using single-molecule real-time sequencing data and characterized insertions found in the assembled genome. We identified 3691 insertions ranging from 100 bps to ~10,000 bps in the assembled genome relative to the international reference sequence (GRCh38). To validate and characterize these insertions, we mapped short-reads from 1070 Japanese individuals and 728 individuals from eight other populations to insertions integrated into GRCh38. With this result, we constructed JRGv1 (Japanese Reference Genome version 1) by integrating the 903 verified insertions, totaling 1,086,173 bases, shared by at least two Japanese individuals into GRCh38. We also constructed decoyJRGv1 by concatenating 3559 verified insertions, totaling 2,536,870 bases, shared by at least two Japanese individuals or by six other assemblies. This assembly improved the alignment ratio by 0.4% on average. These results demonstrate the importance of refining the reference assembly and creating a population-specific reference genome. JRGv1 and decoyJRGv1 are available at the JRG website.

DOI： 10.1038/s41439-019-0057-7
CD45+CD326+ Cells are Predictive of Poor Prognosis in Non-Small Cell Lung Cancer Patients. 査読国際誌

Kota Ishizawa, Mie Yamanaka, Yuriko Saiki, Eisaku Miyauchi, Shinichi Fukushige, Tetsuya Akaishi, Atsuko Asao, Takahiro Mimori, Ryota Saito, Yutaka Tojo, Riu Yamashita, Michiaki Abe, Akira Sakurada, Nhu-An Pham, Ming Li, Yoshinori Okada, Tadashi Ishii, Naoto Ishii, Seiichi Kobayashi, Masao Nagasaki, Masakazu Ichinose, Ming-Sound Tsao, Akira Horii

Clinical cancer research : an official journal of the American Association for Cancer Research 25 ( 22 ) 6756 - 6763 2019年11月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1158/1078-0432.CCR-19-0545
Correction to: High-resolution melt analysis enables simple genotyping of complicated polymorphisms of codon 18 rendering the NUDT15 diplotype. 査読

Kakuta Y, Izumiyama Y, Okamoto D, Nakano T, Ichikawa R, Naito T, Moroi R, Kuroha M, Kanazawa Y, Kimura T, Shiga H, Kudo H, Minegishi N, Kawai Y, Tokunaga K, Nagasaki M, Kinouchi Y, Suzuki Y, Masamune A, MENDEL study group

Journal of gastroenterology 55 ( 1 ) 67 - 77 2019年11月

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記述言語：英語掲載種別：研究論文（学術雑誌）

Correction to: High-resolution melt analysis enables simple genotyping of complicated polymorphisms of codon 18 rendering the NUDT15 diplotype.
Background The genetic variants of NUDT15 have been verified to induce adverse events (AEs) of thiopurines. Codon 139 variants are frequently observed in Asians, while multiple variants are seen in codon 18 which also cause AEs including the European ancestry. The purpose of this study is to establish a technique capable of the simple genotyping of NUDT15 codon 18 and to evaluate its efficacy. Methods A high-resolution melt (HRM) technique is performed to simply determine genotypes. The accuracy of HRM analysis was evaluated with DNAs from 1245 Japanese patients with inflammatory bowel diseases. Subsequently, another group of 572 patients was analyzed to verify the method. The diplotypes and the frequency of their AEs were estimated on the basis of codon 18 and 139 genotypes. Results The HRM analysis enabled the correct identification of the three main genotypes, ref/ref, ref/ins, and ref/V18I, in 1236 of 1241 cases. All rare genotypes including ref/del were identified as the impossible-to-determine group, the proper diagnosis rate was 99.6%. In the verification test using other samples, the diagnosis rate was 99.7%. By estimating diplotypes using both codon 18 and 139 genotypes, 2.74% and 2.13% of Japanese patients with Arg/Arg and Arg/Cys of codon 139 have a lower enzymatic activity of NUDT15 and a higher risk for adverse responses than those estimated by codon 139 genotypes alone. Conclusions Our study showed that HRM method enables simple genotyping of complicated codon 18 variants essential to haplotype estimation of the NUDT15.

DOI： 10.1007/s00535-019-01646-x
High-resolution melt analysis enables simple genotyping of complicated polymorphisms of codon 18 rendering the NUDT15 diplotype. 査読

Kakuta Y, Izumiyama Y, Okamoto D, Nakano T, Ichikawa R, Naito T, Moroi R, Kuroha M, Kanazawa Y, Kimura T, Shiga H, Kudo H, Minegishi N, Kawai Y, Tokunaga K, Nagasaki M, Kinouchi Y, Suzuki Y, Masasmune A, MENDEL study group

Journal of gastroenterology 55 ( 1 ) 67 - 77 2019年10月

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記述言語：英語掲載種別：研究論文（学術雑誌）

High-resolution melt analysis enables simple genotyping of complicated polymorphisms of codon 18 rendering the NUDT15 diplotype.
Background The genetic variants of NUDT15 have been verified to induce adverse events (AEs) of thiopurines. Codon 139 variants are frequently observed in Asians, while multiple variants are seen in codon 18 which also cause AEs including the European ancestry. The purpose of this study is to establish a technique capable of the simple genotyping of NUDT15 codon 18 and to evaluate its efficacy. Methods A high-resolution melt (HRM) technique is performed to simply determine genotypes. The accuracy of HRM analysis was evaluated with DNAs from 1245 Japanese patients with inflammatory bowel diseases. Subsequently, another group of 572 patients was analyzed to verify the method. The diplotypes and the frequency of their AEs were estimated on the basis of codon 18 and 139 genotypes. Results The HRM analysis enabled the correct identification of the three main genotypes, ref/ref, ref/ins, and ref/V18I, in 1236 of 1241 cases. All rare genotypes including ref/del were identified as the impossible-to-determine group, the proper diagnosis rate was 99.6%. In the verification test using other samples, the diagnosis rate was 99.7%. By estimating diplotypes using both codon 18 and 139 genotypes, 2.74% and 2.13% of Japanese patients with Arg/Arg and Arg/Cys of codon 139 have a lower enzymatic activity of NUDT15 and a higher risk for adverse responses than those estimated by codon 139 genotypes alone. Conclusions Our study showed that HRM method enables simple genotyping of complicated codon 18 variants essential to haplotype estimation of the NUDT15.

DOI： 10.1007/s00535-019-01638-x
Genome-wide association meta-analysis and Mendelian randomization analysis confirm the influence of ALDH2 on sleep durationin the Japanese population. 査読国際誌

Takeshi Nishiyama, Masahiro Nakatochi, Atsushi Goto, Motoki Iwasaki, Tsuyoshi Hachiya, Yoichi Sutoh, Atsushi Shimizu, Chaochen Wang, Hideo Tanaka, Miki Watanabe, Akihiro Hosono, Yuya Tamai, Tamaki Yamada, Taiki Yamaji, Norie Sawada, Kentaro Fukumoto, Kotaro Otsuka, Kozo Tanno, Hiroaki Tomita, Kaname Kojima, Masao Nagasaki, Atsushi Hozawa, Asahi Hishida, Tae Sasakabe, Yuichiro Nishida, Megumi Hara, Hidemi Ito, Isao Oze, Yohko Nakamura, Haruo Mikami, Rie Ibusuki, Toshiro Takezaki, Teruhide Koyama, Nagato Kuriyama, Kaori Endoh, Kiyonori Kuriki, Tanvir C Turin, Takashima Naoyuki, Sakurako Katsuura-Kamano, Hirokazu Uemura, Rieko Okada, Sayo Kawai, Mariko Naito, Yukihide Momozawa, Michiaki Kubo, Makoto Sasaki, Masayuki Yamamoto, Shoichiro Tsugane, Kenji Wakai, Sadao Suzuki

Sleep 42 ( 6 ) 2019年6月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1093/sleep/zsz046
3.5KJPNv2: an allele frequency panel of 3552 Japanese individuals including the X chromosome. 査読国際誌

Shu Tadaka, Fumiki Katsuoka, Masao Ueki, Kaname Kojima, Satoshi Makino, Sakae Saito, Akihito Otsuki, Chinatsu Gocho, Mika Sakurai-Yageta, Inaho Danjoh, Ikuko N Motoike, Yumi Yamaguchi-Kabata, Matsuyuki Shirota, Seizo Koshiba, Masao Nagasaki, Naoko Minegishi, Atsushi Hozawa, Shinichi Kuriyama, Atsushi Shimizu, Jun Yasuda, Nobuo Fuse, Gen Tamiya, Masayuki Yamamoto, Kengo Kinoshita

Human genome variation 6 28 - 28 2019年6月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1038/s41439-019-0059-5
A 12-kb structural variation in progressive myoclonic epilepsy was newly identified by long-read whole-genome sequencing. 査読国際誌

Takeshi Mizuguchi, Takeshi Suzuki, Chihiro Abe, Ayako Umemura, Katsushi Tokunaga, Yosuke Kawai, Minoru Nakamura, Masao Nagasaki, Kengo Kinoshita, Yasunobu Okamura, Satoko Miyatake, Noriko Miyake, Naomichi Matsumoto

Journal of human genetics 64 ( 5 ) 359 - 368 2019年5月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1038/s10038-019-0569-5
A Genome-wide Association Study Identifying RAP1A as a Novel Susceptibility Gene for Crohn's Disease in Japanese Individuals. 査読国際誌

Yoichi Kakuta, Yosuke Kawai, Takeo Naito, Atsushi Hirano, Junji Umeno, Yuta Fuyuno, Zhenqiu Liu, Dalin Li, Takeru Nakano, Yasuhiro Izumiyama, Ryo Ichikawa, Daisuke Okamoto, Hiroshi Nagai, Shin Matsumoto, Katsutoshi Yamamoto, Naonobu Yokoyama, Hirofumi Chiba, Yusuke Shimoyama, Motoyuki Onodera, Rintaro Moroi, Masatake Kuroha, Yoshitake Kanazawa, Tomoya Kimura, Hisashi Shiga, Katsuya Endo, Kenichi Negoro, Jun Yasuda, Motohiro Esaki, Katsushi Tokunaga, Minoru Nakamura, Takayuki Matsumoto, Dermot P B McGovern, Masao Nagasaki, Yoshitaka Kinouchi, Tooru Shimosegawa, Atsushi Masamune

Journal of Crohn's & colitis 13 ( 5 ) 648 - 658 2019年4月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1093/ecco-jcc/jjy197
Construction of full-length Japanese reference panel of class I HLA genes with single-molecule, real-time sequencing 査読

Takahiro Mimori, Jun Yasuda, Yoko Kuroki, Tomoko F. Shibata, Fumiki Katsuoka, Sakae Saito, Naoki Nariai, Akira Ono, Naomi Nakai-Inagaki, Kazuharu Misawa, Keiko Tateno, Yosuke Kawai, Nobuo Fuse, Atsushi Hozawa, Shinichi Kuriyama, Junichi Sugawara, Naoko Minegishi, Kichiya Suzuki, Kengo Kinoshita, Masao Nagasaki, Masayuki Yamamoto

The Pharmacogenomics Journal 19 ( 2 ) 136 - 146 2019年4月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1038/s41397-017-0010-4
Estimating carrier frequencies of newborn screening disorders using a whole-genome reference panel of 3552 Japanese individuals. 査読国際誌

Yamaguchi-Kabata Y, Yasuda J, Uruno A, Shimokawa K, Koshiba S, Suzuki Y, Fuse N, Kawame H, Tadaka S, Nagasaki M, Kojima K, Katsuoka F, Kumada K, Tanabe O, Tamiya G, Yaegashi N, Kinoshita K, Yamamoto M, Kure S, Tohoku Medical Megabank Project, Study Group

Human genetics 138 ( 4 ) 389 - 409 2019年3月

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記述言語：英語掲載種別：研究論文（学術雑誌）

Estimating carrier frequencies of newborn screening disorders using a whole-genome reference panel of 3552 Japanese individuals.
Incidence rates of Mendelian diseases vary among ethnic groups, and frequencies of variant types of causative genes also vary among human populations. In this study, we examined to what extent we can predict population frequencies of recessive disorders from genomic data, and explored better strategies for variant interpretation and classification. We used a whole-genome reference panel from 3552 general Japanese individuals constructed by the Tohoku Medical Megabank Organization (ToMMo). Focusing on 32 genes for 17 congenital metabolic disorders included in newborn screening (NBS) in Japan, we identified reported and predicted pathogenic variants through variant annotation, interpretation, and multiple ways of classifications. The estimated carrier frequencies were compared with those from the Japanese NBS data based on 1,949,987 newborns from a previous study. The estimated carrier frequency based on genomic data with a recent guideline of variant interpretation for the PAH gene, in which defects cause hyperphenylalaninemia (HPA) and phenylketonuria (PKU), provided a closer estimate to that by the observed incidence than the other methods. In contrast, the estimated carrier frequencies for SLC25A13, which causes citrin deficiency, were much higher compared with the incidence rate. The results varied greatly among the 11 NBS diseases with single responsible genes; the possible reasons for departures from the carrier frequencies by reported incidence rates were discussed. Of note, (1) the number of pathogenic variants increases by including additional lines of evidence, (2) common variants with mild effects also contribute to the actual frequency of patients, and (3) penetrance of each variant remains unclear.

DOI： 10.1007/s00439-019-01998-7
NFKB1 and MANBA Confer Disease Susceptibility to Primary Biliary Cholangitis via Independent Putative Primary Functional Variants 査読国際誌

Hitomi Yuki, Nakatani Ken, Kojima Kaname, Nishida Nao, Kawai Yosuke, Kawashima Minae, Aiba Yoshihiro, Nagasaki Masao, Nakamura Minoru, Tokunaga Katsushi

CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY 7 ( 3 ) 515 - 532 2019年2月

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記述言語：英語掲載種別：研究論文（学術雑誌）

NFKB1 and MANBA Confer Disease Susceptibility to Primary Biliary Cholangitis via Independent Putative Primary Functional Variants
BACKGROUND & AIMS: Primary biliary cholangitis (PBC) is a chronic and cholestatic liver disease that eventually leads to cirrhosis and hepatic failure. We recently identified several susceptibility genes included NFKB1 and MANBA for PBC in the Japanese population by genome-wide association study. However, the primary functional variants in the NFKB1/MANBA region and the molecular mechanism for conferring disease susceptibility to PBC have not yet been clarified. METHODS: We performed high-density association mapping based on a single-nucleotide polymorphism (SNP) imputation analysis, using data from a whole-genome sequence reference panel of 1070 Japanese individuals and the previous genome-wide association study (1389 PBC patients, 1508 healthy controls). Among SNPs (P < 5.0 × 10-7) in the NFKB1/MANBA region, putative primary functional variants and the molecular mechanism for conferring disease susceptibility to PBC were identified by in silico/in vitro functional analysis. RESULTS: Among the SNPs in the NFKB1/MANBA region, rs17032850 and rs227361, which changed the binding of transcription factors lymphoid enhancer-binding factor 1 (LEF-1) and retinoid X receptor α (RXRα), respectively, were identified as putative primary functional variants that regulate gene expression. In addition, expression-quantitative trait locus data and gene editing using a clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 system supported the potential role of rs17032850 and rs227361 in regulating NFKB1 and MANBA expression, respectively. CONCLUSIONS: We identified independent putative primary functional variants in NFKB1/MANBA and showed the distinct molecular mechanism by which each putative primary functional variant conferred susceptibility to PBC. Our approach was useful to dissect the pathogenesis not only of PBC, but also other digestive diseases in which NFKB1/MANBA has been reported as a susceptibility locus.

DOI： 10.1016/j.jcmgh.2018.11.006
Correction: Allele-specific DNA methylation of disease susceptibility genes in Japanese patients with inflammatory bowel disease. 査読国際誌

Chiba H, Kakuta Y, Kinouchi Y, Kawai Y, Watanabe K, Nagao M, Naito T, Onodera M, Moroi R, Kuroha M, Kanazawa Y, Kimura T, Shiga H, Endo K, Negoro K, Nagasaki M, Unno M, Shimosegawa T

PloS one 14 ( 2 ) e0212148 2019年2月

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記述言語：英語

Correction: Allele-specific DNA methylation of disease susceptibility genes in Japanese patients with inflammatory bowel disease.
[This corrects the article DOI: 10.1371/journal.pone.0194036.].

DOI： 10.1371/journal.pone.0212148
Maternity Log study: a longitudinal lifelog monitoring and multiomics analysis for the early prediction of complicated pregnancy. 査読

Sugawara J, Ochi D, Yamashita R, Yamauchi T, Saigusa D, Wagata M, Obara T, Ishikuro M, Tsunemoto Y, Harada Y, Shibata T, Mimori T, Kawashima J, Katsuoka F, Igarashi-Takai T, Ogishima S, Metoki H, Hashizume H, Fuse N, Minegishi N, Koshiba S, Tanabe O, Kuriyama S, Kinoshita K, Kure S, Yaegashi N, Yamamoto M, Hiyama S, Nagasaki M

BMJ open 9 ( 2 ) e025939 2019年2月

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記述言語：英語掲載種別：研究論文（学術雑誌）

Maternity Log study: a longitudinal lifelog monitoring and multiomics analysis for the early prediction of complicated pregnancy.
Purpose A prospective cohort study for pregnant women, the Maternity Log study, was designed to construct a time-course high-resolution reference catalogue of bioinformatic data in pregnancy and explore the associations between genomic and environmental factors and the onset of pregnancy complications, such as hypertensive disorders of pregnancy, gestational diabetes mellitus and preterm labour, using continuous lifestyle monitoring combined with multiomics data on the genome, transcriptome, proteome, metabolome and microbiome.Participants Pregnant women were recruited at the timing of first routine antenatal visits at Tohoku University Hospital, Sendai, Japan, between September 2015 and November 2016. Of the eligible women who were invited, 65.4% agreed to participate, and a total of 302 women were enrolled. The inclusion criteria were age >= 20 years and the ability to access the internet using a smartphone in the Japanese language.Findings to date Study participants uploaded daily general health information including quality of sleep, condition of bowel movements and the presence of nausea, pain and uterine contractions. Participants also collected physiological data, such as body weight, blood pressure, heart rate and body temperature, using multiple home healthcare devices. The mean upload rate for each lifelog item was ranging from 67.4% (fetal movement) to 85.3% (physical activity), and the total number of data points was over 6 million. Biospecimens, including maternal plasma, serum, urine, saliva, dental plaque and cord blood, were collected for multiomics analysis.Future plans Lifelog and multiomics data will be used to construct a time-course high-resolution reference catalogue of pregnancy. The reference catalogue will allow us to discover relationships among multidimensional phenotypes and novel risk markers in pregnancy for the future personalised early prediction of pregnancy complications.

DOI： 10.1136/bmjopen-2018-025939
Genome analyses for the Tohoku Medical Megabank Project towards establishment of personalized healthcare. 査読国際誌

Jun Yasuda, Kengo Kinoshita, Fumiki Katsuoka, Inaho Danjoh, Mika Sakurai-Yageta, Ikuko N Motoike, Yoko Kuroki, Sakae Saito, Kaname Kojima, Matsuyuki Shirota, Daisuke Saigusa, Akihito Otsuki, Junko Kawashima, Yumi Yamaguchi-Kabata, Shu Tadaka, Yuichi Aoki, Takahiro Mimori, Kazuki Kumada, Jin Inoue, Satoshi Makino, Miho Kuriki, Nobuo Fuse, Seizo Koshiba, Osamu Tanabe, Masao Nagasaki, Gen Tamiya, Ritsuko Shimizu, Takako Takai-Igarashi, Soichi Ogishima, Atsushi Hozawa, Shinichi Kuriyama, Junichi Sugawara, Akito Tsuboi, Hideyasu Kiyomoto, Tadashi Ishii, Hiroaki Tomita, Naoko Minegishi, Yoichi Suzuki, Kichiya Suzuki, Hiroshi Kawame, Hiroshi Tanaka, Yasuyuki Taki, Nobuo Yaegashi, Shigeo Kure, Fuji Nagami, Kenjiro Kosaki, Yoichi Sutoh, Tsuyoshi Hachiya, Atsushi Shimizu, Makoto Sasaki, Masayuki Yamamoto

Journal of biochemistry 165 ( 2 ) 139 - 158 2019年2月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1093/jb/mvy096
POGLUT1, the putative effector gene driven by rs2293370 in primary biliary cholangitis susceptibility locus chromosome 3q13.33. 査読

Hitomi Y, Ueno K, Kawai Y, Nishida N, Kojima K, Kawashima M, Aiba Y, Nakamura H, Kouno H, Kouno H, Ohta H, Sugi K, Nikami T, Yamashita T, Katsushima S, Komeda T, Ario K, Naganuma A, Shimada M, Hirashima N, Yoshizawa K, Makita F, Furuta K, Kikuchi M, Naeshiro N, Takahashi H, Mano Y, Yamashita H, Matsushita K, Tsunematsu S, Yabuuchi I, Nishimura H, Shimada Y, Yamauchi K, Komatsu T, Sugimoto R, Sakai H, Mita E, Koda M, Nakamura Y, Kamitsukasa H, Sato T, Nakamuta M, Masaki N, Takikawa H, Tanaka A, Ohira H, Zeniya M, Abe M, Kaneko S, Honda M, Arai K, Arinaga-Hino T, Hashimoto E, Taniai M, Umemura T, Joshita S, Nakao K, Ichikawa T, Shibata H, Takaki A, Yamagiwa S, Seike M, Sakisaka S, Takeyama Y, Harada M, Senju M, Yokosuka O, Kanda T, Ueno Y, Ebinuma H, Himoto T, Murata K, Shimoda S, Nagaoka S, Abiru S, Komori A, Migita K, Ito M, Yatsuhashi H, Maehara Y, Uemoto S, Kokudo N, Nagasaki M, Tokunaga K, Nakamura M

Scientific reports 9 ( 1 ) 102 2019年1月

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記述言語：その他掲載種別：研究論文（学術雑誌）

POGLUT1, the putative effector gene driven by rs2293370 in primary biliary cholangitis susceptibility locus chromosome 3q13.33.

DOI： 10.1038/s41598-018-36490-1
Susceptibility Loci for Tanning Ability in the Japanese Population Identified by a Genome-Wide Association Study from the Tohoku Medical Megabank Project Cohort Study. 査読

139 ( 7 ) 1605 - 1608.e13 2019年1月

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記述言語：英語

DOI： 10.1016/j.jid.2019.01.015
時系列ライフログと妊娠糖尿病の関連解析

熊谷沙津希, 越智大介, 山内隆史, 和形麻衣子, 長崎正朗, 菅原準一

糖尿病と妊娠 18 ( 3 ) S - 115 2018年11月

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記述言語：日本語
Identification of a two-SNP PLA2R1 Haplotype and HLA-DRB1 Alleles as Primary Risk Associations in Idiopathic Membranous Nephropathy. 査読

Latt KZ, Honda K, Thiri M, Hitomi Y, Omae Y, Sawai H, Kawai Y, Teraguchi S, Ueno K, Nagasaki M, Mabuchi A, Kaga H, Komatsuda A, Tokunaga K, Noiri E

Scientific reports 8 ( 1 ) 15576 2018年10月

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記述言語：その他

Identification of a two-SNP PLA2R1 Haplotype and HLA-DRB1 Alleles as Primary Risk Associations in Idiopathic Membranous Nephropathy.

DOI： 10.1038/s41598-018-33612-7
Time-Series Filtering for Replicated Observations via a Kernel Approximate Bayesian Computation 査読

Takanori Hasegawa, Kaname Kojima, Yosuke Kawai, Masao Nagasaki

IEEE Transactions on Signal Processing 66 ( 23 ) 6148 - 6161 2018年10月

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記述言語：英語掲載種別：研究論文（学術雑誌）

Time-Series Filtering for Replicated Observations via a Kernel Approximate Bayesian Computation

DOI： 10.1109/TSP.2018.2872864
Functional characterization of 40 CYP2B6 allelic variants by assessing efavirenz 8-hydroxylation. 査読国際誌

Watanabe T, Saito T, Rico EMG, Hishinuma E, Kumondai M, Maekawa M, Oda A, Saigusa D, Saito S, Yasuda J, Nagasaki M, Minegishi N, Yamamoto M, Yamaguchi H, Mano N, Hirasawa N, Hiratsuka M

Biochemical pharmacology 156 420 - 430 2018年9月

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記述言語：英語掲載種別：研究論文（学術雑誌）

Functional characterization of 40 CYP2B6 allelic variants by assessing efavirenz 8-hydroxylation.
Genetic variations within cytochrome P450 2B6 (CYP2B6) contribute to inter-individual variation in the metabolism of clinically important drugs, including cyclophosphamide, bupropion, methadone and efavirenz (EFZ). In this study, we performed an in vitro analysis of 40 CYP2B6 allelic variant proteins including seven novel variants identified in 1070 Japanese individuals. Wild-type and 39 variant proteins were heterologously expressed in 293FT cells to estimate the kinetic parameters (Km, Vmax, and CLint) of EFZ 8-hydroxylation and 7-ethoxy-4-trifluoromethylcoumarin (7-ETC) O-deethylation activities. The concentrations of CYP2B6 variant holo-enzymes were measured by using carbon monoxide (CO)-reduced difference spectroscopy, and the wild-type and 28 variants showed a peak at 450 nm. The kinetic parameters were measured for the wild-type and 24 variant proteins. The values for the remaining 15 variants could not be determined because the enzymatic activity was not detected at the highest substrate concentration used. Compared to wild-type, six variants showed significantly decreased EFZ 8-hydroxylation CLint values, while these values were significantly increased in another six variants, including CYP2B6.6. Although 7-ETC O-deethylation CLint values of CYP2B6 variants did not differ significantly from that of CYP2B6.1, the CLint ratios obtained for 7-ETC O-deethylation were highly correlated with EFZ 8-hydroxylation. Furthermore, three-dimensional structural modeling analysis was performed to elucidate the mechanism of changes in the kinetics of CYP2B6 variants. Our findings could provide evidence of the specific metabolic activities of the CYP2B6 proteins encoded by these variant alleles.

DOI： 10.1016/j.bcp.2018.09.010
全ゲノムシークエンス解析を用いた感冒薬関連重症薬疹(CM-SJS/TEN)発症に関わる遺伝要因の網羅的探索

人見祐基, Khor Seik-Soon, 上田真由美, 河合洋介, 外園千恵, 木下茂, 長崎正朗, 徳永勝士

25 ( 2Suppl. ) 89 - 89 2018年9月

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記述言語：日本語
NUDT15 codon 139 is the best pharmacogenetic marker for predicting thiopurine-induced severe adverse events in Japanese patients with inflammatory bowel disease: a multicenter study. 査読

Yoichi Kakuta, Yosuke Kawai, Daisuke Okamoto, Tetsuya Takagawa, Kentaro Ikeya, Hirotake Sakuraba, Atsushi Nishida, Shoko Nakagawa, Miki Miura, Takahiko Toyonaga, Kei Onodera, Masaru Shinozaki, Yoh Ishiguro, Shinta Mizuno, Masahiro Takahara, Shunichi Yanai, Ryota Hokari, Tomoo Nakagawa, Hiroshi Araki, Satoshi Motoya, Takeo Naito, Rintaro Moroi, Hisashi Shiga, Katsuya Endo, Taku Kobayashi, Makoto Naganuma, Sakiko Hiraoka, Takayuki Matsumoto, Shiro Nakamura, Hiroshi Nakase, Tadakazu Hisamatsu, Makoto Sasaki, Hiroyuki Hanai, Akira Andoh, Masao Nagasaki, Yoshitaka Kinouchi, Tooru Shimosegawa, Atsushi Masamune, Yasuo Suzuki

Journal of gastroenterology 53 ( 9 ) 1065 - 1078 2018年9月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1007/s00535-018-1486-7
Development and application of a rapid and sensitive genotyping method for pharmacogene variants using the single-stranded tag hybridization chromatographic printed-array strip (STH-PAS). 査読国際誌

Kumondai M, Ito A, Hishinuma E, Kikuchi A, Saito T, Takahashi M, Tsukada C, Saito S, Yasuda J, Nagasaki M, Minegishi N, Yamamoto M, Kaneko A, Teramoto I, Kimura M, Hirasawa N, Hiratsuka M

Drug metabolism and pharmacokinetics 33 ( 6 ) epub - epub 2018年8月

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記述言語：英語掲載種別：研究論文（学術雑誌）

Development and application of a rapid and sensitive genotyping method for pharmacogene variants using the single-stranded tag hybridization chromatographic printed-array strip (STH-PAS).
Genetic polymorphisms contribute to inter-individual variability in the metabolism of multiple clinical drugs, including warfarin, thiopurines, primaquine, and aminoglycosides. A rapid and sensitive clinical assessment of various genome biomarkers is, therefore, required to predict the individual responsiveness of each patient to these drugs. In this study, we developed a novel genotyping method for the detection of nine pharmacogene variants that are important in the prediction of drug efficiency and toxicity. This genotyping method uses competitive allele-specific PCR and a single-stranded tag hybridization chromatographic printed-array strip (STH-PAS) that can unambiguously determine the presence or absence of the gene variant by displaying visible blue lines on the chromatographic printed-array strip. Notably, the results of our STH-PAS method were in 100% agreement with those obtained using standard Sanger sequencing and KASP assay genotyping methods for CYP4F2 gene deletion. Moreover, the results were obtained within 90 min, including the PCR amplification and signal detection processes. The sensitive and rapid nature of this novel method make it ideal for clinical genetic testing to predict drug efficacy and toxicity, and in doing so will aid in the development of individualized medicine and better patient care.

DOI： 10.1016/j.dmpk.2018.08.003
Strong Association of the HLA-DR/DQ Locus with Childhood Steroid-Sensitive Nephrotic Syndrome in the Japanese Population. 査読国際誌

Xiaoyuan Jia, Tomoko Horinouchi, Yuki Hitomi, Akemi Shono, Seik-Soon Khor, Yosuke Omae, Kaname Kojima, Yosuke Kawai, Masao Nagasaki, Yoshitsugu Kaku, Takayuki Okamoto, Yoko Ohwada, Kazuhide Ohta, Yusuke Okuda, Rika Fujimaru, Ken Hatae, Naonori Kumagai, Emi Sawanobori, Hitoshi Nakazato, Yasufumi Ohtsuka, Koichi Nakanishi, Yuko Shima, Ryojiro Tanaka, Akira Ashida, Koichi Kamei, Kenji Ishikura, Kandai Nozu, Katsushi Tokunaga, Kazumoto Iijima

Journal of the American Society of Nephrology : JASN 29 ( 8 ) 2189 - 2199 2018年8月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1681/ASN.2017080859
Functional Characterization of 21 Allelic Variants of Dihydropyrimidine Dehydrogenase Identified in 1070 Japanese Individuals. 査読国際誌

Hishinuma E, Narita Y, Saito S, Maekawa M, Akai F, Nakanishi Y, Yasuda J, Nagasaki M, Yamamoto M, Yamaguchi H, Mano N, Hirasawa N, Hiratsuka M

Drug metabolism and disposition: the biological fate of chemicals 46 ( 8 ) 1083 - 1090 2018年8月

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記述言語：英語掲載種別：研究論文（学術雑誌）

Functional Characterization of 21 Allelic Variants of Dihydropyrimidine Dehydrogenase Identified in 1070 Japanese Individuals.
Dihydropyrimidine dehydrogenase (DPD, EC 1.3.1.2), encoded by the DPYD gene, is the rate-limiting enzyme in the degradation pathway of endogenous pyrimidine and fluoropyrimidine drugs such as 5-fluorouracil (5-FU). DPD catalyzes the reduction of uracil, thymine, and 5-FU. In Caucasians, DPYD mutations, including DPYD*2A, DPYD*13, c.2846A>T, and c.1129-5923C>G/hapB3, are known to contribute to interindividual variations in the toxicity of 5-FU; however, none of these DPYD polymorphisms has been identified in the Asian population. Recently, 21 DPYD allelic variants, including some novel single-nucleotide variants (SNVs), were identified in 1070 healthy Japanese individuals by analyzing their whole-genome sequences (WGSs), but the functional alterations caused by these variants remain unknown. In this study, in vitro analysis was performed on 22 DPD allelic variants by transiently expressing wild-type DPD and 21 DPD variants in 293FT cells and characterizing their enzymatic activities using 5-FU as a substrate. DPD expression levels and dimeric forms were determined using immunoblotting and blue-native PAGE, respectively. Additionally, the values of three kinetic parameters-the Michaelis constant (Km ), maximum velocity (Vmax ), and intrinsic clearance (CLint = Vmax/Km )-were determined for the reduction of 5-FU. Eleven variants exhibited significantly decreased intrinsic clearance compared with wild-type DPD. Moreover, the band patterns observed in the immunoblots of blue-native gels indicated that DPD dimerization is required for enzymatic activity in DPD. Thus, the detection of rare DPYD variants might facilitate severe adverse effect prediction of 5-FU-based chemotherapy in the Japanese population.

DOI： 10.1124/dmd.118.081737
Regional genetic differences among Japanese populations and performance of genotype imputation using whole-genome reference panel of the Tohoku Medical Megabank Project. 査読国際誌

Jun Yasuda, Fumiki Katsuoka, Inaho Danjoh, Yosuke Kawai, Kaname Kojima, Masao Nagasaki, Sakae Saito, Yumi Yamaguchi-Kabata, Shu Tadaka, Ikuko N Motoike, Kazuki Kumada, Mika Sakurai-Yageta, Osamu Tanabe, Nobuo Fuse, Gen Tamiya, Koichiro Higasa, Fumihiko Matsuda, Nobufumi Yasuda, Motoki Iwasaki, Makoto Sasaki, Atsushi Shimizu, Kengo Kinoshita, Masayuki Yamamoto

BMC genomics 19 ( 1 ) 551 - 551 2018年7月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1186/s12864-018-4942-0
網羅的全ゲノム解析法を駆使した感冒薬関連重症薬疹における疾患感受性遺伝子の同定

人見祐基, 上田真由美, 長崎正朗, 徳永勝士

臨床薬理の進歩 ( 39 ) 164 - 170 2018年6月

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記述言語：日本語

感冒薬関連重症薬疹を対象に全エクソーム解析を実施し、ゲノムワイド関連解析から取りこぼされた可能性のある遺伝要因の探索を試みた。眼障害のある感冒薬関連スティーブンス・ジョンソン症候群/中毒性表皮壊死融解症患者117例(男性46例、女性71例、平均41.5±17.1歳)を対象とした。全ゲノムシークエンス解析から得られた一塩基多型(SNP)の遺伝子型情報を比較したところ、有意水準を満たすSNPが2ヶ所以上検出された新規疾患感受性遺伝子として14ヶ所が同定された。次に、GTEX portal databaseを用いた量的形質遺伝子座(e-QTL)解析およびPolyphen2を用いたタンパク産物への影響の検証を実施した。その結果、PDIA6のrs4807、SEC16Bのrs7413442、PNCTのrs2249060などのSNPは、遺伝子発現量との強い関連を示していた。一方、MUC16のrs11670318、F5のrs6027、FAT2のrs1432862などのSNPは、その遺伝子がコードするタンパク産物へ重大な影響を与えていることが予測された。
Omics research project on prospective cohort studies from the Tohoku Medical Megabank Project. 査読国際誌

Seizo Koshiba, Ikuko Motoike, Daisuke Saigusa, Jin Inoue, Matsuyuki Shirota, Yasutake Katoh, Fumiki Katsuoka, Inaho Danjoh, Atsushi Hozawa, Shinichi Kuriyama, Naoko Minegishi, Masao Nagasaki, Takako Takai-Igarashi, Soichi Ogishima, Nobuo Fuse, Shigeo Kure, Gen Tamiya, Osamu Tanabe, Jun Yasuda, Kengo Kinoshita, Masayuki Yamamoto

Genes to cells : devoted to molecular & cellular mechanisms 23 ( 6 ) 406 - 417 2018年6月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1111/gtc.12588
Analysis of Müller glia specific genes and their histone modification using Hes1-promoter driven EGFP expressing mouse. 査読国際誌

8 ( 1 ) 8946 - 8946 2018年6月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1038/s41598-018-27041-9
NELFCD and CTSZ loci are associated with jaundice-stage progression in primary biliary cholangitis in the Japanese population. 査読国際誌

Nao Nishida, Yoshihiro Aiba, Yuki Hitomi, Minae Kawashima, Kaname Kojima, Yosuke Kawai, Kazuko Ueno, Hitomi Nakamura, Noriyo Yamashiki, Tomohiro Tanaka, Sumito Tamura, Akira Mori, Shintaro Yagi, Yuji Soejima, Tomoharu Yoshizumi, Mitsuhisa Takatsuki, Atsushi Tanaka, Kenichi Harada, Shinji Shimoda, Atsumasa Komori, Susumu Eguchi, Yoshihiko Maehara, Shinji Uemoto, Norihiro Kokudo, Masao Nagasaki, Katsushi Tokunaga, Minoru Nakamura

Scientific reports 8 ( 1 ) 8071 - 8071 2018年5月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1038/s41598-018-26369-6
Population-scale whole genome sequencing identifies 271 highly polymorphic short tandem repeats from Japanese population. 査読国際誌

Satoshi Hirata, Kaname Kojima, Kazuharu Misawa, Olivier Gervais, Yosuke Kawai, Masao Nagasaki

Heliyon 4 ( 5 ) e00625 - e00625 2018年5月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1016/j.heliyon.2018.e00625
Identification of somatic mutations in postmortem human brains by whole genome sequencing and their implications for psychiatric disorders. 査読国際誌

Masaki Nishioka, Miki Bundo, Junko Ueda, Fumiki Katsuoka, Yukuto Sato, Yoko Kuroki, Takao Ishii, Wataru Ukai, Shigeo Murayama, Eri Hashimoto, Masao Nagasaki, Jun Yasuda, Kiyoto Kasai, Tadafumi Kato, Kazuya Iwamoto

Psychiatry and clinical neurosciences 72 ( 4 ) 280 - 294 2018年4月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1111/pcn.12632
日本人原発性胆汁性胆管炎の疾患感受性遺伝子POU2AF1、PRKCBの役割の検討

相葉佳洋, 原田憲一, 伊東正博, 人見祐基, 植野和子, 小森敦正, 八橋弘, 長崎正朗, 徳永勝士, 中村稔

肝臓 59 ( Suppl.1 ) A455 - A455 2018年4月

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記述言語：日本語
Clinical and genetic risk factors for decreased bone mineral density in Japanese patients with inflammatory bowel disease. 査読国際誌

Naito T, Yokoyama N, Kakuta Y, Ueno K, Kawai Y, Onodera M, Moroi R, Kuroha M, Kanazawa Y, Kimura T, Shiga H, Endo K, Nagasaki M, Masamune A, Kinouchi Y, Shimosegawa T

Journal of gastroenterology and hepatology 33 ( 11 ) epub - epub 2018年3月

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記述言語：英語掲載種別：研究論文（学術雑誌）

Clinical and genetic risk factors for decreased bone mineral density in Japanese patients with inflammatory bowel disease.
BACKGROUND AND AIM: Patients with inflammatory bowel disease (IBD) are at a high risk of low bone mineral density (BMD). Reportedly, clinical and genetic factors cause low BMD in Caucasians; however, studies in non-Caucasian populations remain scarce. METHODS: Clinical risk factors for low BMD were investigated in 266 Japanese patients with IBD, and a genome-wide association analysis (GWAS) was performed using linear regression with associated clinical factors as covariates. Genotyping was performed using a population-optimized genotyping array (Japonica array® ). After quality control, the genotype data of 4 384 682 single-nucleotide polymorphisms (SNPs) from 254 patients with IBD were used for GWAS. RESULTS: Body mass index, age, and disease duration were independently associated with the BMD of the femoral neck (P = 1.41E - 13, 1.04E - 5, and 1.58E - 3, respectively), and body mass index and sex were associated with the BMD of the lumbar spine (P = 6.90E - 10 and 6.84E - 3, respectively). In GWAS, 118 and 42 candidate SNPs of the femoral neck and lumbar spine, respectively, were identified. Among 118, 111 candidate SNPs of the femoral neck were located within the SLC22A23 gene, which is a known IBD susceptibility gene (minimum P = 1.42E - 07). Among 42, 18 candidate SNPs of the lumbar spine were located within the MECOM gene, which is associated with osteopenia (minimum P = 5.86E - 07). Interestingly, none of the known loci showed a significant association with BMD. CONCLUSIONS: Although clinical risk factors for low BMD in IBD were similar to those in the general population, genetic risk factors were rather different.

DOI： 10.1111/jgh.14149
Allele-specific DNA methylation of disease susceptibility genes in Japanese patients with inflammatory bowel disease. 査読国際誌

Hirofumi Chiba, Yoichi Kakuta, Yoshitaka Kinouchi, Yosuke Kawai, Kazuhiro Watanabe, Munenori Nagao, Takeo Naito, Motoyuki Onodera, Rintaro Moroi, Masatake Kuroha, Yoshitake Kanazawa, Tomoya Kimura, Hisashi Shiga, Katsuya Endo, Kenichi Negoro, Masao Nagasaki, Michiaki Unno, Tooru Shimosegawa

PloS one 13 ( 3 ) e0194036 - e0194036 2018年3月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1371/journal.pone.0194036
Evaluation of reported pathogenic variants and their frequencies in a Japanese population based on a whole-genome reference panel of 2049 individuals. 査読国際誌

Yumi Yamaguchi-Kabata, Jun Yasuda, Osamu Tanabe, Yoichi Suzuki, Hiroshi Kawame, Nobuo Fuse, Masao Nagasaki, Yosuke Kawai, Kaname Kojima, Fumiki Katsuoka, Sakae Saito, Inaho Danjoh, Ikuko N Motoike, Riu Yamashita, Seizo Koshiba, Daisuke Saigusa, Gen Tamiya, Shigeo Kure, Nobuo Yaegashi, Yoshio Kawaguchi, Fuji Nagami, Shinichi Kuriyama, Junichi Sugawara, Naoko Minegishi, Atsushi Hozawa, Soichi Ogishima, Hideyasu Kiyomoto, Takako Takai-Igarashi, Kengo Kinoshita, Masayuki Yamamoto

Journal of human genetics 63 ( 2 ) 213 - 230 2018年2月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1038/s10038-017-0347-1
Identification of somatic genetic alterations in ovarian clear cell carcinoma with next generation sequencing 査読

Yusuke Shibuya, Hideki Tokunaga, Sakae Saito, Kazurou Shimokawa, Fumiki Katsuoka, Li Bin, Kaname Kojima, Masao Nagasaki, Masayuki Yamamoto, Nobuo Yaegashi, Jun Yasuda

GENES CHROMOSOMES & CANCER 57 ( 2 ) 51 - 60 2018年2月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1002/gcc.22507
Genetic analysis of Japanese primary open-angle glaucoma patients and clinical characterization of risk alleles near CDKN2B-AS1, SIX6 and GAS7 査読

Yukihiro Shiga, Japan Glaucoma Society Omics Group (JGS-OG), Koji M. Nishiguchi, Yosuke Kawai, Kaname Kojima, Kota Sato, Kosuke Fujita, Mai Takahashi, Kazuko Omodaka, Makoto Araie, Kenji Kashiwagi, Makoto Aihara, Takeshi Iwata, Fumihiko Mabuchi, Mitsuko Takamoto, Mineo Ozaki, Kazuhide Kawase, Nobuo Fuse, Masayuki Yamamoto, Jun Yasuda, Masao Nagasaki, Toru Nakazawa

PLoS ONE 12 ( 12 ) e0186678 - e0186678 2017年12月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1371/journal.pone.0186678
Security controls in an integrated Biobank to protect privacy in data sharing: rationale and study design 査読

Takako Takai-Igarashi, Kengo Kinoshita, Masao Nagasaki, Soichi Ogishima, Naoki Nakamura, Sachiko Nagase, Satoshi Nagaie, Tomo Saito, Fuji Nagami, Naoko Minegishi, Yoichi Suzuki, Kichiya Suzuki, Hiroaki Hashizume, Shinichi Kuriyama, Atsushi Hozawa, Nobuo Yaegashi, Shigeo Kure, Gen Tamiya, Yoshio Kawaguchi, Hiroshi Tanaka, Masayuki Yamamoto

BMC MEDICAL INFORMATICS AND DECISION MAKING 17 ( 1 ) 100 - 100 2017年7月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1186/s12911-017-0494-5
Analysis of Müller glia specific genes and their histone modification using Hes1-promoter driven EGFP expressing mouse. 査読

7 ( 1 ) 3578 - 3578 2017年6月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1038/s41598-017-03874-8
Identification of the functional variant driving ORMDL3 and GSDMB expression in human chromosome 17q12-21 in primary biliary cholangitis 査読

Yuki Hitomi, Kaname Kojima, Minae Kawashima, Yosuke Kawai, Nao Nishida, Yoshihiro Aiba, Michio Yasunami, Masao Nagasaki, Minoru Nakamura, Katsushi Tokunaga

SCIENTIFIC REPORTS 7 ( 1 ) 2904 - 2904 2017年6月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1038/s41598-017-03067-3
A Histologic Categorization of Aqueous Outflow Routes in Familial Open-Angle Glaucoma and Associations With Mutations in the MYOC Gene in Japanese Patients 査読

Teruhiko Hamanaka, Masae Kimura, Tetsuro Sakurai, Nobuo Ishida, Jun Yasuda, Masao Nagasaki, Naoki Nariai, Atsushi Endo, Kei Homma, Fumiki Katsuoka, Yoichi Matsubara, Masayuki Yamamoto, Nobuo Fuse

INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE 58 ( 5 ) 2818 - 2831 2017年5月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1167/iovs.16-20646
Genome-Wide Association Study Identifies TLL1 Variant Associated With Development of Hepatocellular Carcinoma After Eradication of Hepatitis C Virus Infection 査読

Kentaro Matsuura, Hiromi Sawai, Kazuho Ikeo, Shintaro Ogawa, Etsuko Iio, Masanori Isogawa, Noritomo Shimada, Atsumasa Komori, Hidenori Toyoda, Takashi Kumada, Tadashi Namisaki, Hitoshi Yoshiji, Naoya Sakamoto, Mina Nakagawa, Yasuhiro Asahina, Masayuki Kurosaki, Namiki Izumi, Nobuyuki Enomoto, Atsunori Kusakabe, Eiji Kajiwara, Yoshito Itoh, Tatsuya Ide, Akihiro Tamori, Misako Matsubara, Norifumi Kawada, Ken Shirabe, Eiichi Tomita, Masao Honda, Shuichi Kaneko, Sohji Nishina, Atsushi Suetsugu, Yoichi Hiasa, Hisayoshi Watanabe, Takuya Genda, Isao Sakaida, Shuhei Nishiguchi, Koichi Takaguchi, Eiji Tanaka, Junichi Sugihara, Mitsuo Shimada, Yasuteru Kondo, Yosuke Kawai, Kaname Kojima, Masao Nagasaki, Katsushi Tokunaga, Yasuhito Tanaka

GASTROENTEROLOGY 152 ( 6 ) 1383 - 1394 2017年5月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1053/j.gastro.2017.01.041
Genome-wide association study using the ethnicity-specific Japonica array: identification of new susceptibility loci for cold medicine-related Stevens-Johnson syndrome with severe ocular complications 査読

Mayumi Ueta, Hiromi Sawai, Ryosei Shingaki, Yusuke Kawai, Chie Sotozono, Kaname Kojima, Kyung-Chul Yoon, Mee Kum Kim, Kyoung Yul Seo, Choun-Ki Joo, Masao Nagasaki, Shigeru Kinoshita, Katsushi Tokunaga

JOURNAL OF HUMAN GENETICS 62 ( 4 ) 485 - 489 2017年4月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1038/jhg.2016.160
Genome-wide identification of inter-individually variable DNA methylation sites improves the efficacy of epigenetic association studies 査読

Tsuyoshi Hachiya, Ryohei Furukawa, Yuh Shiwa, Hideki Ohmomo, Kanako Ono, Fumiki Katsuoka, Masao Nagasaki, Jun Yasuda, Nobuo Fuse, Kengo Kinoshita, Masayuki Yamamoto, Kozo Tanno, Mamoru Satoh, Ryujin Endo, Makoto Sasaki, Kiyomi Sakata, Seiichiro Kobayashi, Kuniaki Ogasawara, Jiro Hitomi, Kenji Sobue, Atsushi Shimizu

NPJ GENOMIC MEDICINE 2 11 - 11 2017年4月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1038/s41525-017-0016-5
LRRK2 but not ATG16L1 is associated with Paneth cell defect in Japanese Crohn's disease patients. 査読国際誌

Liu TC, Naito T, Liu Z, VanDussen KL, Haritunians T, Li D, Endo K, Kawai Y, Nagasaki M, Kinouchi Y, McGovern DP, Shimosegawa T, Kakuta Y, Stappenbeck TS

JCI insight 2 ( 6 ) e91917 - e91917 2017年3月

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記述言語：英語掲載種別：研究論文（学術雑誌）

LRRK2 but not ATG16L1 is associated with Paneth cell defect in Japanese Crohn's disease patients.
BACKGROUND. Morphological patterns of Paneth cells are a prognostic biomarker in Western Crohn's disease (CD) patients, and are associated with autophagy-associated ATG16L1 and NOD2 variants. We hypothesized that genetic determinants of Paneth cell phenotype in other ethnic CD cohorts are distinct but also involved in autophagy. METHODS. We performed a hypothesis-driven analysis of 56 single nucleotide polymorphisms (SNPs) associated with CD susceptibility or known to affect Paneth cell function in 110 Japanese CD patients who underwent ileal resection. We subsequently performed a genome-wide association analysis. Paneth cell phenotype was determined by defensin-5 immunofluorescence. Selected genotype-Paneth cell defect correlations were compared to a Western CD cohort (n = 164). RESULTS. The average percentage of abnormal Paneth cells in Japanese CD was similar to Western CD (P = 0.87), and abnormal Paneth cell phenotype was also associated with early recurrence (P = 0.013). In contrast to Western CD, ATG16L1 T300A was not associated with Paneth cell defect in Japanese CD (P = 0.20). Among the 56 selected SNPs, only LRRK2 M2397T showed significant association with Paneth cell defect (P = 3.62 × 10-4), whereas in the Western CD cohort it was not (P = 0.76). Pathway analysis of LRRK2 and other candidate genes with P less than 5 × 10-4 showed connections with known CD susceptibility genes and links to autophagy and TNF-α networks. CONCLUSIONS. We found dichotomous effects of ATG16L1 and LRRK2 on Paneth cell defect between Japanese and Western CD. Genes affecting Paneth cell phenotype in Japanese CD were also associated with autophagy. Paneth cell phenotype also predicted prognosis in Japanese CD. FUNDING. Helmsley Charitable Trust, Doris Duke Foundation (grant 2014103), Japan Society for the Promotion of Science (KAKENHI grants JP15H04805 and JP15K15284), Crohn's and Colitis Foundation grant 274415, NIH (grants 1R56DK095820, K01DK109081, and UL1 TR000448).

DOI： 10.1172/jci.insight.91917
Genome-wide association studies identify PRKCB as a novel genetic susceptibility locus for primary biliary cholangitis in the Japanese population 査読

Minae Kawashima, Yuki Hitomi, Yoshihiro Aiba, Nao Nishida, Kaname Kojima, Yosuke Kawai, Hitomi Nakamura, Atsushi Tanaka, Mikio Zeniya, Etsuko Hashimoto, Hiromasa Ohira, Kazuhide Yamamoto, Masanori Abe, Kazuhiko Nakao, Satoshi Yamagiwa, Shuichi Kaneko, Masao Honda, Takeji Umemura, Takafumi Ichida, Masataka Seike, Shotaro Sakisaka, Masaru Harada, Osamu Yokosuka, Yoshiyuki Ueno, Michio Senju, Tatsuo Kanda, Hidetaka Shibata, Takashi Himoto, Kazumoto Murata, Yasuhiro Miyake, Hirotoshi Ebinuma, Makiko Taniai, Satoru Joshita, Toshiki Nikami, Hajime Ota, Hiroshi Kouno, Hirotaka Kouno, Makoto Nakamuta, Nobuyoshi Fukushima, Motoyuki Kohjima, Tatsuji Komatsu, Toshiki Komeda, Yukio Ohara, Toyokichi Muro, Tsutomu Yamashita, Kaname Yoshizawa, Yoko Nakamura, Masaaki Shimada, Noboru Hirashima, Kazuhiro Sugi, Keisuke Ario, Eiichi Takesaki, Atsushi Naganuma, Hiroshi Mano, Haruhiro Yamashita, Kouki Matsushita, Kazuhiko Yamauchi, Fujio Makita, Hideo Nishimura, Kiyoshi Furuta, Naohiro Takahashi, Masahiro Kikuchi, Naohiko Masaki, Tomohiro Tanaka, Sumito Tamura, Akira Mori, Shintaro Yagi, Ken Shirabe, Atsumasa Komori, Kiyoshi Migita, Masahiro Ito, Shinya Nagaoka, Seigo Abiru, Hiroshi Yatsuhashi, Michio Yasunami, Shinji Shimoda, Kenichi Harada, Hiroto Egawa, Yoshihiko Maehara, Shinji Uemoto, Norihiro Kokudo, Hajime Takikawa, Hiromi Ishibashi, Kazuaki Chayama, Masashi Mizokami, Masao Nagasaki, Katsushi Tokunaga, Minoru Nakamura

HUMAN MOLECULAR GENETICS 26 ( 3 ) 650 - 659 2017年2月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1093/hmg/ddw406
Monitoring of minimal residual disease in early T-cell precursor acute lymphoblastic leukaemia by next-generation sequencing 査読

Xiaoqing Pan, Naoki Nariai, Noriko Fukuhara, Sakae Saito, Yukuto Sato, Fumiki Katsuoka, Kaname Kojima, Yoko Kuroki, Inaho Danjoh, Rumiko Saito, Shin Hasegawa, Yoko Okitsu, Aiko Kondo, Yasushi Onishi, Fuji Nagami, Hideyasu Kiyomoto, Atsushi Hozawa, Nobuo Fuse, Masao Nagasaki, Ritsuko Shimizu, Jun Yasuda, Hideo Harigae, Masayuki Yamamoto

BRITISH JOURNAL OF HAEMATOLOGY 176 ( 2 ) 318 - 321 2017年1月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1111/bjh.13948
STR-realigner: a realignment method for short tandem repeat regions. 査読

Kojima K, Kawai Y, Misawa K, Mimori T, Nagasaki M

BMC genomics 17 ( 1 ) 991 - 991 2016年12月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1186/s12864-016-3294-x
Conditional Rod Photoreceptor Ablation Reveals Sall1 as a Microglial Marker and Regulator of Microglial Morphology in the Retina 査読

Hideto Koso, Asano Tsuhako, Chen-Yi Lai, Yukihiro Baba, Makoto Otsu, Kazuko Ueno, Masao Nagasaki, Yutaka Suzuki, Sumiko Watanabe

GLIA 64 ( 11 ) 2005 - 2024 2016年11月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1002/glia.23038
AP-SKAT: highly-efficient genome-wide rare variant association test. 査読

Hasegawa T, Kojima K, Kawai Y, Misawa K, Mimori T, Nagasaki M

BMC genomics 17 ( 1 ) 745 - 745 2016年9月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1186/s12864-016-3094-3
妊娠関連疾患の予防・早期発見のためのヘルスケアデータと多層オミックスデータの統合解析を目指して

原田祐希, 越智大介, 山内隆史, 山下理宇, 檜山聡, 長崎正朗, 菅原準一, マタニティログプロジェクトチーム

日本生化学会大会プログラム・講演要旨集 89回 [3P - 253] 2016年9月

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記述言語：日本語
Variants in the UBR1 gene are not associated with chronic pancreatitis in Japan 査読

Atsushi Masamune, Eriko Nakano, Tetsuya Niihori, Shin Hamada, Masao Nagasaki, Yoko Aoki, Tooru Shimosegawa

PANCREATOLOGY 16 ( 5 ) 814 - 818 2016年9月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1016/j.pan.2016.06.662
The Tohoku Medical Megabank Project: Design and Mission 査読

Shinichi Kuriyama, Nobuo Yaegashi, Fuji Nagami, Tomohiko Arai, Yoshio Kawaguchi, Noriko Osumi, Masaki Sakaida, Yoichi Suzuki, Keiko Nakayama, Hiroaki Hashizume, Gen Tamiya, Hiroshi Kawame, Kichiya Suzuki, Atsushi Hozawa, Naoki Nakaya, Masahiro Kikuya, Hirohito Metoki, Ichiro Tsuji, Nobuo Fuse, Hideyasu Kiyomoto, Junichi Sugawara, Akito Tsuboi, Shinichi Egawa, Kiyoshi Ito, Koichi Chida, Tadashi Ishii, Hiroaki Tomita, Yasuyuki Taki, Naoko Minegishi, Naoto Ishii, Jun Yasuda, Kazuhiko Igarashi, Ritsuko Shimizu, Masao Nagasaki, Seizo Koshiba, Kengo Kinoshita, Soichi Ogishima, Takako Takai-Igarashi, Teiji Tominaga, Osamu Tanabe, Noriaki Ohuchi, Toru Shimosegawa, Shigeo Kure, Hiroshi Tanaka, Sadayoshi Ito, Jiro Hitomi, Kozo Tanno, Motoyuki Nakamura, Kuniaki Ogasawara, Seiichiro Kobayashi, Kiyomi Sakata, Mamoru Satoh, Atsushi Shimizu, Makoto Sasaki, Ryujin Endo, Kenji Sobue, Masayuki Yamamoto

JOURNAL OF EPIDEMIOLOGY 26 ( 9 ) 493 - 511 2016年9月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.2188/jea.JE20150268
The structural origin of metabolic quantitative diversity 査読

Seizo Koshiba, Ikuko Motoike, Kaname Kojima, Takanori Hasegawa, Matsuyuki Shirota, Tomo Saito, Daisuke Saigusa, Inaho Danjoh, Fumiki Katsuoka, Soichi Ogishima, Yosuke Kawai, Yumi Yamaguchi-Kabata, Miyuki Sakurai, Sachiko Hirano, Junichi Nakata, Hozumi Motohashi, Atsushi Hozawa, Shinichi Kuriyama, Naoko Minegishi, Masao Nagasaki, Takako Takai-Igarashi, Nobuo Fuse, Hideyasu Kiyomoto, Junichi Sugawara, Yoichi Suzuki, Shigeo Kure, Nobuo Yaegashi, Osamu Tanabe, Kengo Kinoshita, Jun Yasuda, Masayuki Yamamoto

SCIENTIFIC REPORTS 6 31463 - 31463 2016年8月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1038/srep31463
Short tandem repeat number estimation from paired-end reads for multiple individuals by considering coalescent tree 査読

Kaname Kojima, Yosuke Kawai, Naoki Nariai, Takahiro Mimori, Takanori Hasegawa, Masao Nagasaki

BMC GENOMICS 17 494 - 494 2016年8月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1186/s12864-016-2821-0
Fine-mapping analysis revealed complex pleiotropic effect and tissue-specific regulatory mechanism of TNFSF15 in primary biliary cholangitis, Crohn's disease and leprosy 査読

Yonghu Sun, Astrid Irwanto, Licht Toyo-oka, Myunghee Hong, Hong Liu, Anand Kumar Andiappan, Hyunchul Choi, Yuki Hitomi, Gongqi Yu, Yongxiang Yu, Fangfang Bao, Chuan Wang, Xian Fu, Zhenhua Yue, Honglei Wang, Huimin Zhang, Minae Kawashima, Kaname Kojima, Masao Nagasaki, Minoru Nakamura, Suk-Kyun Yang, Byong Duk Ye, Yosua Denise, Olaf Rotzschke, Kyuyoung Song, Katsushi Tokunaga, Furen Zhang, Jianjun Liu

SCIENTIFIC REPORTS 6 31429 - 31429 2016年8月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1038/srep31429
Transition of differential histone H3 methylation in photoreceptors and other retinal cells during retinal differentiation 査読

Kazuko Ueno, Toshiro Iwagawa, Hiroshi Kuribayashi, Yukihiro Baba, Hiromitsu Nakauchi, Akira Murakami, Masao Nagasaki, Yutaka Suzuki, Sumiko Watanabe

SCIENTIFIC REPORTS 6 29264 - 29264 2016年7月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1038/srep29264
Comparison of Boiling and Robotics Automation Method in DNA Extraction for Metagenomic Sequencing of Human Oral Microbes 査読

Junya Yamagishi, Yukuto Sato, Natsuko Shinozaki, Bin Ye, Akito Tsuboi, Masao Nagasaki, Riu Yamashita

PLOS ONE 11 ( 4 ) e0154389 - e0154389 2016年4月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1371/journal.pone.0154389
A Comprehensive Genomic Analysis Reveals the Genetic Landscape of Mitochondrial Respiratory Chain Complex Deficiencies 査読

Masakazu Kohda, Yoshimi Tokuzawa, Yoshihito Kishita, Hiromi Nyuzuki, Yohsuke Moriyama, Yosuke Mizuno, Tomoko Hirata, Yukiko Yatsuka, Yzumi Yamashita-Sugahara, Yutaka Nakachi, Hidemasa Kato, Akihiko Okuda, Shunsuke Tamaru, Nurun Nahar Borna, Kengo Banshoya, Toshiro Aigaki, Yukiko Sato-Miyata, Kohei Ohnuma, Tsutomu Suzuki, Asuteka Nagao, Hazuki Maehata, Fumihiko Matsuda, Koichiro Higasa, Masao Nagasaki, Jun Yasuda, Masayuki Yamamoto, Takuya Fushimi, Masaru Shimura, Keiko Kaiho-Ichimoto, Hiroko Harashima, Taro Yamazaki, Masato Mori, Kei Murayama, Akira Ohtake, Yasushi Okazaki

PLoS Genetics 12 ( 1 ) e1005679 - e1005679 2016年1月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1371/journal.pgen.1005679
A Bayesian approach for estimating allele-specific expression from RNA-Seq data with diploid genomes 査読

Naoki Nariai, Kaname Kojima, Takahiro Mimori, Yosuke Kawai, Masao Nagasaki

BMC GENOMICS 17 2 - 2 2016年1月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1186/s12864-015-2295-5
Japonica array: improved genotype imputation by designing a population-specific SNP array with 1070 Japanese individuals 査読

Yosuke Kawai, Takahiro Mimori, Kaname Kojima, Naoki Nariai, Inaho Danjoh, Rumiko Saito, Jun Yasuda, Masayuki Yamamoto, Masao Nagasaki

JOURNAL OF HUMAN GENETICS 60 ( 10 ) 581 - 587 2015年10月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1038/jhg.2015.68
Rare variant discovery by deep whole-genome sequencing of 1,070 Japanese individuals 査読

Masao Nagasaki, Jun Yasuda, Fumiki Katsuoka, Naoki Nariai, Kaname Kojima, Yosuke Kawai, Yumi Yamaguchi-Kabata, Junji Yokozawa, Inaho Danjoh, Sakae Saito, Yukuto Sato, Takahiro Mimori, Kaoru Tsuda, Rumiko Saito, Xiaoqing Pan, Satoshi Nishikawa, Shin Ito, Yoko Kuroki, Osamu Tanabe, Nobuo Fuse, Shinichi Kuriyama, Hideyasu Kiyomoto, Atsushi Hozawa, Naoko Minegishi, James Douglas Engel, Kengo Kinoshita, Shigeo Kure, Nobuo Yaegashi, Masayuki Yamamoto

NATURE COMMUNICATIONS 6 8018 - 8018 2015年8月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1038/ncomms9018
Short tandem repeat number estimation from paired-end sequence reads by considering unobserved genealogy of multiple individuals 査読

Kaname Kojima, Yosuke Kawai, Naoki Nariai, Takahiro Mimori, Takanori Hasegawa, Masao Nagasaki

Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics) 9096 422 - 423 2015年8月

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記述言語：英語掲載種別：研究論文（その他学術会議資料等）

DOI： 10.1007/978-3-319-19048-8
Somatic alteration and depleted nuclear expression of BAP1 in human esophageal squamous cell carcinomas 査読

Takahiro Mori, Makiko Sumii, Fumiyoshi Fujishima, Kazuko Ueno, Masao Nagasaki, Chikashi Ishioka, Natsuko Chiba

CANCER RESEARCH 75 2015年8月

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記述言語：英語

DOI： 10.1158/1538-7445.AM2015-4955
Inter-Individual Differences in the Oral Bacteriome Are Greater than Intra-Day Fluctuations in Individuals 査読

Yukuto Sato, Junya Yamagishi, Riu Yamashita, Natsuko Shinozaki, Bin Ye, Takuji Yamada, Masayuki Yamamoto, Masao Nagasaki, Akito Tsuboi

PLOS ONE 10 ( 6 ) e0131607 - e0131607 2015年6月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1371/journal.pone.0131607
Estimating copy numbers of alleles from population-scale high-throughput sequencing data 査読

Takahiro Mimori, Naoki Nariai, Kaname Kojima, Yukuto Sato, Yosuke Kawai, Yumi Yamaguchi-Kabata, Masao Nagasaki

BMC BIOINFORMATICS 16 S4 - S4 2015年1月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1186/1471-2105-16-S1-S4
HLA-VBSeq: accurate HLA typing at full resolution from whole-genome sequencing data 査読

Naoki Nariai, Kaname Kojima, Sakae Saito, Takahiro Mimori, Yukuto Sato, Yosuke Kawai, Yumi Yamaguchi-Kabata, Jun Yasuda, Masao Nagasaki

BMC GENOMICS 16 S7 - S7 2015年1月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1186/1471-2164-16-S2-S7
An efficient quantitation method of next-generation sequencing libraries by using MiSeq sequencer 査読

Fumiki Katsuoka, Junji Yokozawa, Kaoru Tsuda, Shin Ito, Xiaoqing Pan, Masao Nagasaki, Jun Yasuda, Masayuki Yamamoto

ANALYTICAL BIOCHEMISTRY 466 27 - 29 2014年12月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1016/j.ab.2014.08.015
TIGAR2: sensitive and accurate estimation of transcript isoform expression with longer RNA-Seq reads 査読

Naoki Nariai, Kaname Kojima, Takahiro Mimori, Yukuto Sato, Yosuke Kawai, Yumi Yamaguchi-Kabata, Masao Nagasaki

BMC GENOMICS 15 S5 - S5 2014年12月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1186/1471-2164-15-S10-S5
胎生期ストレスが胎児のエピゲノム変化および精神行動に及ぼす影響の特定査読

兪志前, 舟山亮, 植野和子, 成相直樹, 小島要, 小野千晶, 笠原好之, 長崎正朗, 中山啓子, 富田博秋

日本臨床精神神経薬理学会・日本神経精神薬理学会合同年会プログラム・抄録集 24回・44回 204 - 204 2014年11月

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記述言語：日本語
Identification of acquired mutations by whole-genome sequencing in GATA-2 deficiency evolving into myelodysplasia and acute leukemia 査読

Tohru Fujiwara, Noriko Fukuhara, Ryo Funayama, Naoki Nariai, Mayumi Kamata, Takeshi Nagashima, Kaname Kojima, Yasushi Onishi, Yoji Sasahara, Kenichi Ishizawa, Masao Nagasaki, Keiko Nakayama, Hideo Harigae

ANNALS OF HEMATOLOGY 93 ( 9 ) 1515 - 1522 2014年9月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1007/s00277-014-2090-4
Inference of Gene Regulatory Networks Incorporating Multi-Source Biological Knowledge via a State Space Model with L1 Regularization 査読

Takanori Hasegawa, Rui Yamaguchi, Masao Nagasaki, Satoru Miyano, Seiya Imoto

PLOS ONE 9 ( 8 ) e105942 - e105942 2014年8月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1371/journal.pone.0105942
Validation of multiple single nucleotide variation calls by additional exome analysis with a semiconductor sequencer to supplement data of whole-genome sequencing of a human population 査読

Ikuko N. Motoike, Mitsuyo Matsumoto, Inaho Danjoh, Fumiki Katsuoka, Kaname Kojima, Naoki Nariai, Yukuto Sato, Yumi Yamaguchi-Kabata, Shin Ito, Hisaaki Kudo, Ichiko Nishijima, Satoshi Nishikawa, Xiaoqing Pan, Rumiko Saito, Sakae Saito, Tomo Saito, Matsuyuki Shirota, Kaoru Tsuda, Junji Yokozawa, Kazuhiko Igarashi, Naoko Minegishi, Osamu Tanabe, Nobuo Fuse, Masao Nagasaki, Kengo Kinoshita, Jun Yasuda, Masayuki Yamamoto

BMC GENOMICS 15 673 - 673 2014年8月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1186/1471-2164-15-673
SUGAR: graphical user interface-based data refiner for high-throughput DNA sequencing 査読

Yukuto Sato, Kaname Kojima, Naoki Nariai, Yumi Yamaguchi-Kabata, Yosuke Kawai, Mamoru Takahashi, Takahiro Mimori, Masao Nagasaki

BMC GENOMICS 15 664 - 664 2014年8月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1186/1471-2164-15-664
An efficient method of exploring simulation models by assimilating literature and biological observational data 査読

Takanori Hasegawa, Masao Nagasaki, Rui Yamaguchi, Seiya Imoto, Satoru Miyano

BIOSYSTEMS 121 54 - 66 2014年7月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1016/j.biosystems.2014.06.001
SVEM: A Structural Variant Estimation Method Using Multi-mapped Reads on Breakpoints 査読

Tomohiko Ohtsuki, Naoki Nariai, Kaname Kojima, Takahiro Mimori, Yukuto Sato, Yosuke Kawai, Yumi Yamaguchi-Kabata, Testuo Shibuya, Masao Nagasaki

ALGORITHMS FOR COMPUTATIONAL BIOLOGY 8542 208 - 219 2014年7月

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記述言語：英語掲載種別：研究論文（その他学術会議資料等）
CSML2SBML: A novel tool for converting quantitative biological pathway models from CSML into SBML 査読

Chen Li, Masao Nagasaki, Emi Ikeda, Yayoi Sekiya, Satoru Miyano

BIOSYSTEMS 121 22 - 28 2014年7月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1016/j.biosystems.2014.05.004
iSVP: an integrated structural variant calling pipeline from high-throughput sequencing data 査読

Takahiro Mimori, Naoki Nariai, Kaname Kojima, Mamoru Takahashi, Akira Ono, Yukuto Sato, Yumi Yamaguchi-Kabata, Masao Nagasaki

BMC SYSTEMS BIOLOGY 7 S8 - S8 2013年12月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1186/1752-0509-7-S6-S8
A statistical variant calling approach from pedigree information and local haplotyping with phase informative reads 査読

Kaname Kojima, Naoki Nariai, Takahiro Mimori, Mamoru Takahashi, Yumi Yamaguchi-Kabata, Yukuto Sato, Masao Nagasaki

BIOINFORMATICS 29 ( 22 ) 2835 - 2843 2013年11月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1093/bioinformatics/btt503
Recurrent mutations in multiple components of the cohesin complex in myeloid neoplasms. 査読国際誌

Ayana Kon, Lee-Yung Shih, Masashi Minamino, Masashi Sanada, Yuichi Shiraishi, Yasunobu Nagata, Kenichi Yoshida, Yusuke Okuno, Masashige Bando, Ryuichiro Nakato, Shumpei Ishikawa, Aiko Sato-Otsubo, Genta Nagae, Aiko Nishimoto, Claudia Haferlach, Daniel Nowak, Yusuke Sato, Tamara Alpermann, Masao Nagasaki, Teppei Shimamura, Hiroko Tanaka, Kenichi Chiba, Ryo Yamamoto, Tomoyuki Yamaguchi, Makoto Otsu, Naoshi Obara, Mamiko Sakata-Yanagimoto, Tsuyoshi Nakamaki, Ken Ishiyama, Florian Nolte, Wolf-Karsten Hofmann, Shuichi Miyawaki, Shigeru Chiba, Hiraku Mori, Hiromitsu Nakauchi, H Phillip Koeffler, Hiroyuki Aburatani, Torsten Haferlach, Katsuhiko Shirahige, Satoru Miyano, Seishi Ogawa

Nature genetics 45 ( 10 ) 1232 - 7 2013年10月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1038/ng.2731
Profiling of MicroRNA in Human and Mouse ES and iPS Cells Reveals Overlapping but Distinct MicroRNA Expression Patterns 査読

Siti Razila Abdul Razak, Kazuko Ueno, Naoya Takayama, Naoki Nariai, Masao Nagasaki, Rika Saito, Hideto Koso, Chen-Yi Lai, Miyako Murakami, Koichiro Tsuji, Tatsuo Michiue, Hiromitsu Nakauchi, Makoto Otsu, Sumiko Watanabe

PLOS ONE 8 ( 9 ) e73532 - e73532 2013年9月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1371/journal.pone.0073532
TIGAR: transcript isoform abundance estimation method with gapped alignment of RNA-Seq data by variational Bayesian inference 査読

Naoki Nariai, Osamu Hirose, Kaname Kojima, Masao Nagasaki

BIOINFORMATICS 29 ( 18 ) 2292 - 2299 2013年9月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1093/bioinformatics/btt381
Wnt3a stimulates maturation of impaired neutrophils developed from severe congenital neutropenia patient-derived pluripotent stem cells 査読

Takafumi Hiramoto, Yasuhiro Ebihara, Yoko Mizoguchi, Kazuhiro Nakamura, Kiyoshi Yamaguchi, Kazuko Ueno, Naoki Nariai, Shinji Mochizuki, Shohei Yamamoto, Masao Nagasaki, Yoichi Furukawa, Kenzaburo Tani, Hiromitsu Nakauchi, Masao Kobayashi, Kohichiro Tsuji

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 110 ( 8 ) 3023 - 3028 2013年2月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1073/pnas.1217039110
XiP: a computational environment to create, extend and share workflows 査読

Masao Nagasaki, Andre Fujita, Yayoi Sekiya, Ayumu Saito, Emi Ikeda, Chen Li, Satoru Miyano

BIOINFORMATICS 29 ( 1 ) 137 - 139 2013年1月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1093/bioinformatics/bts630
ChopSticks: High-resolution analysis of homozygous deletions by exploiting concordant read pairs 査読

Tomohiro Yasuda, Shin Suzuki, Masao Nagasaki, Satoru Miyano

BMC BIOINFORMATICS 13 279 - 279 2012年10月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1186/1471-2105-13-279
Transposon mutagenesis identifies genes that transform neural stem cells into glioma-initiating cells 査読

Hideto Koso, Haruna Takeda, Christopher Chin Kuan Yew, Jerrold M. Ward, Naoki Nariai, Kazuko Ueno, Masao Nagasaki, Sumiko Watanabe, Alistair G. Rust, David J. Adams, Neal G. Copeland, Nancy A. Jenkins

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 109 ( 44 ) E2998 - E3007 2012年10月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1073/pnas.1215899109
Epidermal Growth Factor Receptor Tyrosine Kinase Defines Critical Prognostic Genes of Stage I Lung Adenocarcinoma 査読

Mai Yamauchi, Rui Yamaguchi, Asuka Nakata, Takashi Kohno, Masao Nagasaki, Teppei Shimamura, Seiya Imoto, Ayumu Saito, Kazuko Ueno, Yousuke Hatanaka, Ryo Yoshida, Tomoyuki Higuchi, Masaharu Nomura, David G. Beer, Jun Yokota, Satoru Miyano, Noriko Gotoh

PLOS ONE 7 ( 9 ) e43923 - e43923 2012年9月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1371/journal.pone.0043923
A microarray analysis of gnotobiotic mice indicating that microbial exposure during the neonatal period plays an essential role in immune system development 査読

Masahiro Yamamoto, Rui Yamaguchi, Kaori Munakata, Kiyoe Takashima, Mitsue Nishiyama, Kyoji Hioki, Yasuyuki Ohnishi, Masao Nagasaki, Seiya Imoto, Satoru Miyano, Atsushi Ishige, Kenji Watanabe

BMC GENOMICS 13 335 - 335 2012年7月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1186/1471-2164-13-335
Whole-genome sequencing of liver cancers identifies etiological influences on mutation patterns and recurrent mutations in chromatin regulators 査読

Akihiro Fujimoto, Yasushi Totoki, Tetsuo Abe, Keith A. Boroevich, Fumie Hosoda, Ha Hai Nguyen, Masayuki Aoki, Naoya Hosono, Michiaki Kubo, Fuyuki Miya, Yasuhito Arai, Hiroyuki Takahashi, Takuya Shirakihara, Masao Nagasaki, Tetsuo Shibuya, Kaoru Nakano, Kumiko Watanabe-Makino, Hiroko Tanaka, Hiromi Nakamura, Jun Kusuda, Hidenori Ojima, Kazuaki Shimada, Takuji Okusaka, Masaki Ueno, Yoshinobu Shigekawa, Yoshiiku Kawakami, Koji Arihiro, Hideki Ohdan, Kunihito Gotoh, Osamu Ishikawa, Shun-ichi Ariizumi, Masakazu Yamamoto, Terumasa Yamada, Kazuaki Chayama, Tomoo Kosuge, Hiroki Yamaue, Naoyuki Kamatani, Satoru Miyano, Hitoshi Nakagama, Yusuke Nakamura, Tatsuhiko Tsunoda, Tatsuhiro Shibata, Hidewaki Nakagawa

NATURE GENETICS 44 ( 7 ) 760 - U182 2012年7月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1038/ng.2291
Identifying Gene Pathways Associated with Cancer Characteristics via Sparse Statistical Methods 査読

Shuichi Kawano, Teppei Shimamura, Atsushi Niida, Seiya Imoto, Rui Yamaguchi, Masao Nagasaki, Ryo Yoshida, Cristin Print, Satoru Miyano

IEEE-ACM TRANSACTIONS ON COMPUTATIONAL BIOLOGY AND BIOINFORMATICS 9 ( 4 ) 966 - 972 2012年7月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1109/TCBB.2012.48
IRView: a database and viewer for protein interacting regions 査読

Shigeo Fujimori, Naoya Hirai, Kazuyo Masuoka, Tomohiro Oshikubo, Tatsuhiro Yamashita, Takanori Washio, Ayumu Saito, Masao Nagasaki, Satoru Miyano, Etsuko Miyamoto-Sato

BIOINFORMATICS 28 ( 14 ) 1949 - 1950 2012年7月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1093/bioinformatics/bts289
ClipCrop: a tool for detecting structural variations with single-base resolution using soft-clipping information 査読

Shin Suzuki, Tomohiro Yasuda, Yuichi Shiraishi, Satoru Miyano, Masao Nagasaki

BMC BIOINFORMATICS 12 S7 - S7 2011年12月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1186/1471-2105-12-S14-S7
High Performance Hybrid Functional Petri Net Simulations of Biological Pathway Models on CUDA 査読

Georgios Chalkidis, Masao Nagasaki, Satoru Miyano

IEEE-ACM TRANSACTIONS ON COMPUTATIONAL BIOLOGY AND BIOINFORMATICS 8 ( 6 ) 1545 - 1556 2011年11月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1109/TCBB.2010.118
Frequent pathway mutations of splicing machinery in myelodysplasia 査読

Kenichi Yoshida, Masashi Sanada, Yuichi Shiraishi, Daniel Nowak, Yasunobu Nagata, Ryo Yamamoto, Yusuke Sato, Aiko Sato-Otsubo, Ayana Kon, Masao Nagasaki, George Chalkidis, Yutaka Suzuki, Masashi Shiosaka, Ryoichiro Kawahata, Tomoyuki Yamaguchi, Makoto Otsu, Naoshi Obara, Mamiko Sakata-Yanagimoto, Ken Ishiyama, Hiraku Mori, Florian Nolte, Wolf-Karsten Hofmann, Shuichi Miyawaki, Sumio Sugano, Claudia Haferlach, H. Phillip Koeffler, Lee-Yung Shih, Torsten Haferlach, Shigeru Chiba, Hiromitsu Nakauchi, Satoru Miyano, Seishi Ogawa

NATURE 478 ( 7367 ) 64 - 69 2011年10月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1038/nature10496
CSO validator: improving manual curation workflow for biological pathways 査読

Euna Jeong, Masao Nagasaki, Emi Ikeda, Yayoi Sekiya, Ayumu Saito, Satoru Miyano

BIOINFORMATICS 27 ( 17 ) 2471 - 2472 2011年9月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1093/bioinformatics/btr395
Hybrid Petri net based modeling for biological pathway simulation 査読

Hiroshi Matsuno, Masao Nagasaki, Satoru Miyano

NATURAL COMPUTING 10 ( 3 ) 1099 - 1120 2011年9月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1007/s11047-009-9164-6
A Novel Network Profiling Analysis Reveals System Changes in Epithelial-Mesenchymal Transition 査読

Teppei Shimamura, Seiya Imoto, Yukako Shimada, Yasuyuki Hosono, Atsushi Niida, Masao Nagasaki, Rui Yamaguchi, Takashi Takahashi, Satoru Miyano

PLOS ONE 6 ( 6 ) e20804 - e20804 2011年6月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1371/journal.pone.0020804
Systems biology model repository for macrophage pathway simulation 査読

Masao Nagasaki, Ayumu Saito, Andre Fujita, Georg Tremmel, Kazuko Ueno, Emi Ikeda, Euna Jeong, Satoru Miyano

BIOINFORMATICS 27 ( 11 ) 1591 - 1593 2011年6月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1093/bioinformatics/btr173
Estimating Genome-Wide Gene Networks Using Nonparametric Bayesian Network Models on Massively Parallel Computers 査読

Y Tamada, S Imoto, H Araki, M Nagasaki, C Print, D S Charnock-Jones, S Miyano

IEEE/ACM Transactions on Computational Biology and Bioinformatics 8 ( 3 ) 683 - 697 2011年5月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1109/tcbb.2010.68
Comprehensive Pharmacogenomic Pathway Screening by Data Assimilation 査読

Takanori Hasegawa, Rui Yamaguchi, Masao Nagasaki, Seiya Imoto, Satoru Miyano

BIOINFORMATICS RESEARCH AND APPLICATIONS 6674 160 - 171 2011年5月

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記述言語：英語掲載種別：研究論文（その他学術会議資料等）
MIRACH: efficient model checker for quantitative biological pathway models 査読

Chuan Hock Koh, Masao Nagasaki, Ayumu Saito, Chen Li, Limsoon Wong, Satoru Miyano

BIOINFORMATICS 27 ( 5 ) 734 - 735 2011年3月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1093/bioinformatics/btq727
Ontology-based instance data validation for high-quality curated biological pathways 査読

Euna Jeong, Masao Nagasaki, Kazuko Ueno, Satoru Miyano

BMC BIOINFORMATICS 12 S8 - S8 2011年2月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1186/1471-2105-12-S1-S8
Cell illustrator 4.0: a computational platform for systems biology. 査読国際誌

Nagasaki M, Saito A, Jeong E, Li C, Kojima K, Ikeda E, Miyano S

Studies in health technology and informatics 162 160 - 181 2011年2月

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記述言語：英語掲載種別：研究論文（学術雑誌）

Cell illustrator 4.0: a computational platform for systems biology.
Cell Illustrator is a software platform for Systems Biology that uses the concept of Petri net for modeling and simulating biopathways. It is intended for biological scientists working at bench. The latest version of Cell Illustrator 4.0 uses Java Web Start technology and is enhanced with new capabilities, including: automatic graph grid layout algorithms using ontology information; tools using Cell System Markup Language (CSML) 3.0 and Cell System Ontology 3.0; parameter search module; high-performance simulation module; CSML database management system; conversion from CSML model to programming languages (FORTRAN, C, C++, Java, Python and Perl); import from SBML, CellML, and BioPAX; and, export to SVG and HTML. Cell Illustrator employs an extension of hybrid Petri net in an object-oriented style so that biopathway models can include objects such as DNA sequence, molecular density, 3D localization information, transcription with frame-shift, translation with codon table, as well as biochemical reactions.
Model-free unsupervised gene set screening based on information enrichment in expression profiles 査読

Atushi Niida, Seiya Imoto, Rui Yamaguchi, Masao Nagasaki, Andre Fujita, Teppei Shimamura, Satoru Miyano

BIOINFORMATICS 26 ( 24 ) 3090 - 3097 2010年12月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1093/bioinformatics/btq592
Phosphoproteomics-Based Modeling Defines the Regulatory Mechanism Underlying Aberrant EGFR Signaling 査読

Shinya Tasaki, Masao Nagasaki, Hiroko Kozuka-Hata, Kentaro Semba, Noriko Gotoh, Seisuke Hattori, Jun-ichiro Inoue, Tadashi Yamamoto, Satoru Miyano, Sumio Sugano, Masaaki Oyama

PLOS ONE 5 ( 11 ) e13926 - e13926 2010年11月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1371/journal.pone.0013926
Whole-genome sequencing and comprehensive variant analysis of a Japanese individual using massively parallel sequencing 査読

Akihiro Fujimoto, Hidewaki Nakagawa, Naoya Hosono, Kaoru Nakano, Tetsuo Abe, Keith A. Boroevich, Masao Nagasaki, Rui Yamaguchi, Tetsuo Shibuya, Michiaki Kubo, Satoru Miyano, Yusuke Nakamura, Tatsuhiko Tsunoda

NATURE GENETICS 42 ( 11 ) 931 - U39 2010年11月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1038/ng.691
Identification of granger causality between gene sets 査読

Journal of Bioinformatics and Computational Biology 8 ( 4 ) 679 - 701 2010年8月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1142/S0219720010004860
DA 1.0: parameter estimation of biological pathways using data assimilation approach 査読

Chuan Hock Koh, Masao Nagasaki, Ayumu Saito, Limsoon Wong, Satoru Miyano

BIOINFORMATICS 26 ( 14 ) 1794 - 1796 2010年7月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1093/bioinformatics/btq276
An efficient biological pathway layout algorithm combining grid-layout and spring embedder for complicated cellular location information 査読

Kaname Kojima, Masao Nagasaki, Satoru Miyano

BMC BIOINFORMATICS 11 335 - 335 2010年6月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1186/1471-2105-11-335
The systems approach to the prespore-specific activation of sigma factor SigF in Bacillus subtilis 査読

Jin Hwan Do, Masao Nagasaki, Satoru Miyano

BIOSYSTEMS 100 ( 3 ) 178 - 184 2010年6月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1016/j.biosystems.2010.03.002
Gene Set-Based Module Discovery Decodes cis-Regulatory Codes Governing Diverse Gene Expression across Human Multiple Tissues 査読

Atsushi Niida, Seiya Imoto, Rui Yamaguchi, Masao Nagasaki, Satoru Miyano

PLOS ONE 5 ( 6 ) e10910 - e10910 2010年6月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1371/journal.pone.0010910
Inferring dynamic gene networks under varying conditions for transcriptomic network comparison 査読

Teppei Shimamura, Seiya Imoto, Rui Yamaguchi, Masao Nagasaki, Satoru Miyano

BIOINFORMATICS 26 ( 8 ) 1064 - 1072 2010年4月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1093/bioinformatics/btq080
Time-dependent structural transformation analysis to high-level Petri net model with active state transition diagram 査読

Chen Li, Masao Nagasaki, Ayumu Saito, Satoru Miyano

BMC SYSTEMS BIOLOGY 4 39 - 39 2010年4月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1186/1752-0509-4-39
A novel meta-analysis approach of cancer transcriptomes reveals prevailing transcriptional networks in cancer cells. 査読

Atsushi Niida, Seiya Imoto, Masao Nagasaki, Rui Yamaguchi, Satoru Miyano

Genome informatics. International Conference on Genome Informatics 22 121 - 31 2010年1月

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記述言語：英語掲載種別：研究論文（学術雑誌）
A state space representation of VAR models with sparse learning for dynamic gene networks. 査読

Kojima K, Yamaguchi R, Imoto S, Yamauchi M, Nagasaki M, Yoshida R, Shimamura T, Ueno K, Higuchi T, Gotoh N, Miyano S

Genome informatics. International Conference on Genome Informatics 22 56 - 68 2010年1月

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記述言語：英語掲載種別：研究論文（学術雑誌）

A state space representation of VAR models with sparse learning for dynamic gene networks.
We propose a state space representation of vector autoregressive model and its sparse learning based on L1 regularization to achieve efficient estimation of dynamic gene networks based on time course microarray data. The proposed method can overcome drawbacks of the vector autoregressive model and state space model; the assumption of equal time interval and lack of separation ability of observation and systems noises in the former method and the assumption of modularity of network structure in the latter method. However, in a simple implementation the proposed model requires the calculation of large inverse matrices in a large number of times during parameter estimation process based on EM algorithm. This limits the applicability of the proposed method to a relatively small gene set. We thus introduce a new calculation technique for EM algorithm that does not require the calculation of inverse matrices. The proposed method is applied to time course microarray data of lung cells treated by stimulating EGF receptors and dosing an anticancer drug, Gefitinib. By comparing the estimated network with the control network estimated using non-treated lung cells, perturbed genes by the anticancer drug could be found, whose up- and down-stream genes in the estimated networks may be related to side effects of the anticancer drug.
Ligand-based gene expression profiling reveals novel roles of glucocorticoid receptor in cardiac metabolism 査読

Noritada Yoshikawa, Masao Nagasaki, Motoaki Sano, Satori Tokudome, Kazuko Ueno, Noriaki Shimizu, Seiya Imoto, Satoru Miyano, Makoto Suematsu, Keiichi Fukuda, Chikao Morimoto, Hirotoshi Tanaka

AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM 296 ( 6 ) E1363 - E1373 2009年6月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1152/ajpendo.90767.2008
Orengedokuto and berberine improve indomethacin-induced small intestinal injury via adenosine 査読

Yoko Watanabe-Fukuda, Masahiro Yamamoto, Naoko Miura, Masato Fukutake, Atsushi Ishige, Rui Yamaguchi, Masao Nagasaki, Ayumu Saito, Seiya Imoto, Satoru Miyano, Junzo Takeda, Kenji Watanabe

JOURNAL OF GASTROENTEROLOGY 44 ( 5 ) 380 - 389 2009年5月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1007/s00535-009-0005-2
Analysis of PPARα-dependent and PPARα-independent transcript regulation following fenofibrate treatment of human endothelial cells 査読

12 ( 3 ) 221 - 229 2009年4月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1007/s10456-009-9142-8
Simulation-based model checking approach to cell fate specification during Caenorhabditis elegans vulval development by hybrid functional Petri net with extension 査読

Chen Li, Masao Nagasaki, Kazuko Ueno, Satoru Miyano

BMC SYSTEMS BIOLOGY 3 42 - 42 2009年4月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1186/1752-0509-3-42
Recursive regularization for inferring gene networks from time-course gene expression profiles 査読

Teppei Shimamura, Seiya Imoto, Rui Yamaguchi, Andre Fujita, Masao Nagasaki, Satoru Miyano

BMC SYSTEMS BIOLOGY 3 41 - 41 2009年4月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1186/1752-0509-3-41
BFL: a node and edge betweenness based fast layout algorithm for large scale networks 査読

Tatsunori B. Hashimoto, Masao Nagasaki, Kaname Kojima, Satoru Miyano

BMC BIOINFORMATICS 10 19 - 19 2009年1月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1186/1471-2105-10-19
Bayesian learning of biological pathways on genomic data assimilation 査読

Ryo Yoshida, Masao Nagasaki, Rui Yamaguchi, Seiya Imoto, Satoru Miyano, Tomoyuki Higuchi

BIOINFORMATICS 24 ( 22 ) 2592 - 2601 2008年11月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1093/bioinformatics/btn483
ExonMiner: Web service for analysis of GeneChip Exon array data 査読

Kazuyuki Numata, Ryo Yoshida, Masao Nagasaki, Ayumu Saito, Seiya Imoto, Satoru Miyano

BMC BIOINFORMATICS 9 494 - 494 2008年11月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1186/1471-2105-9-494
Fast grid layout algorithm for biological networks with sweep calculation 査読

Kaname Kojima, Masao Nagasaki, Satoru Miyano

BIOINFORMATICS 24 ( 12 ) 1433 - 1441 2008年6月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1093/bioinformatics/btn196
Systematic reconstruction of TRANSPATH data into Cell System Markup Language 査読

Masao Nagasaki, Ayumu Saito, Chen Li, Euna Jeong, Satoru Miyano

BMC SYSTEMS BIOLOGY 2 53 - 53 2008年6月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1186/1752-0509-2-53
An efficient grid layout algorithm for biological networks utilizing various biological attributes 査読

Kaname Kojima, Masao Nagasaki, Euna Jeong, Mitsuru Kato, Satoru Miyano

BMC BIOINFORMATICS 8 76 - 76 2007年3月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1186/1471-2105-8-76
AYUMS: an algorithm for completely automatic quantitation based on LC-MS/MS proteome data and its application to the analysis of signal transduction 査読

Ayumu Saito, Masao Nagasaki, Masaaki Oyama, Hiroko Kozuka-Hata, Kentaro Semba, Sumio Sugano, Tadashi Yamamoto, Satoru Miyano

BMC BIOINFORMATICS 8 15 - 15 2007年1月

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記述言語：英語掲載種別：研究論文（学術雑誌）

DOI： 10.1186/1741-2105-8-15
Simulation-based validation of the p53 transcriptional activity with hybrid functional Petri net 査読

Atsushi Doi, Masao Nagasaki, Hiroshi Matsuno, Satoru Miyano

In Silico Biology 6 ( 1-2 ) 1 - 13 2006年1月

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記述言語：英語掲載種別：研究論文（学術雑誌）
[Dynamic pathway modeling language: CSML]. 査読

Nagasaki M, Doi A, Miyano S

Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme 50 ( 16 Suppl ) 2269 - 2274 2005年12月

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記述言語：英語掲載種別：研究論文（学術雑誌）

[Dynamic pathway modeling language: CSML].

▼全件表示

書籍等出版物

遺伝学の百科事典

公益財団法人遺伝学普及会日本遺伝学会編（範囲: Pp198）

丸善出版 2022年1月

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遺伝子医学36号,特集：Common disease解析の最前線

Gervais Olivier, 河合洋介, 長﨑正朗

メディカルドゥ 2021年4月

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記述言語：その他
ジャポニカアレイの設計と全ゲノムインピュテーションによる活用

河合洋介, 三森隆広, 小島要, 成相直樹, 長﨑正朗（担当：共著）

月刊メディカル・サイエンス・ダイジェスト 2015年5月

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記述言語：その他

講演・口頭発表等

Genome-wide Meta and Gene Ontology Analysis for High Myopia

Kazuya Morino, Masahiro Miyake, Akira Meguro, Masao Nagasaki, Yuki Mori, Shin-ya Nakao, Takuro Kamei, Nao Aisu, Akitaka Tsujikawa

American Academy of Ophthalmology 2023 2023年11月

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開催年月日： 2023年11月

記述言語：日本語

国名：日本国
抗原提示補助シグナル分子の遺伝的バリアントに起因する自己免疫疾患感受性の分子機序の解明

人見祐基、植野和子、相葉佳洋、西田奈央、河合洋介、川嶋実苗、 Seik-Soon Khor、長崎正朗、徳永勝士、中村稔

第31回日本組織適合性学会大会 2023年9月

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開催年月日： 2023年9月

記述言語：日本語

開催地：一橋大学学術総合センター国名：日本国
未来医療へのヒト情報解析基盤構築と実装

長﨑　正朗

未来社会デザイン統括本部＆データ駆動イノベーション推進本部　合同シンポジウム2023 2023年9月

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開催年月日： 2023年9月

記述言語：日本語

開催地：九州大学伊都キャンパス椎木講堂国名：日本国
ヒトゲノム情報や臨床情報のセキュリティと情報解析の取り組みについて

長﨑正朗

αxSC2023Q セキュリティとスーパーコンピュータシンポジウム 2023年7月

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開催年月日： 2023年7月

記述言語：日本語

開催地：九州大学情報基盤研究開発センター国名：日本国
ヒトゲノムと臨床情報の統合解析に向けたハイブリッドクラウド基盤構築とパブリッククラウドの活用

長﨑正朗

教育と研究のDXフォーラム 2023年7月

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開催年月日： 2023年7月

記述言語：日本語

開催地：福岡会場西南学院大学コミュニティセンター国名：日本国
ハイブリッドクラウドを用いたゲノム情報に基づく構造多型パネルの構築とアノテーション（口頭発表）

長﨑正朗

学際大規模情報基盤共同利用・共同研究拠点第 15回シンポジウム 2023年7月

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開催年月日： 2023年7月

記述言語：日本語

開催地：オンライン(Tokyo) 国名：日本国
難病レジストリ研究の運用構築支援とデータシェアリング推進（難病プラットフォーム活動報告）

第27回日本医療情報学会春季学術大会 2023年6月

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開催年月日： 2023年6月 - 2023年7月

記述言語：日本語

開催地：沖縄コンベンションセンター国名：日本国
自己免疫疾患感受性遺伝子に起因する発症機序の解明におけるCRISPR/Cas9の活用 Utilization of CRISPR/Cas9 to elucidate the pathogenesis of autoimmune disease-susceptibility genes

人見祐基, 植野和子, 相葉佳洋, 西田奈央, 河合洋介, 川嶋実苗, Khor Seik-Soon, 長﨑正朗, 徳永勝士, 中村稔 Yuki Hitomi, Kazuko Ueno, Yoshihiro Aiba, Nao Nishida, Yosuke Kawai, Minae Kawashima, Seik-Soon Khor, Masao Nagasaki, Katsushi Tokunaga, Minoru Nakamura

日本ゲノム編集学会　第8回大会 8th Annual Meeting of The Japanese Society for Genome Editing 2023年6月

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開催年月日： 2023年6月

記述言語：日本語

開催地：タワーホール船堀国名：日本国
ハイブリッドクラウド構築とゲノム情報解析の効率的な運用に関した研究

長﨑正朗

学際大規模情報基盤共同利用・共同研究拠点第 13 回シンポジウム 2021年7月

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開催年月日： 2021年7月

記述言語：日本語

国名：その他
尿酸値の失われた遺伝率は、レアバリアントがかなりの部分を説明する

三澤計治, 長谷川嵩矩, 三島英換, Promsuk Jutabha, 大内基司, 小島要, 河合洋介, 松尾雅文, 安西尚彦, 長崎正朗

日本バイオインフォマティクス学会 2020年9月

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開催年月日： 2020年9月

記述言語：日本語

国名：その他
ゲノム医科学における国内外のヒトゲノム解析の状況およびハイブリッドクラウド計算環境の構築と活用

長﨑正朗

第44回日本分子生物学会年会 2021年12月

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記述言語：日本語

国名：その他
日本人の公開可能な長鎖型集団パネル構築とその意義について

長﨑正朗

PacBio ユーザーグループミーティング 2022 2022年5月

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記述言語：日本語

国名：その他
ハイブリッドクラウド構築とゲノム情報解析の効率的な運用に関した研究

長﨑正朗

学際大規模情報基盤共同利用・共同研究拠点第 14回シンポジウム 2022年7月

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記述言語：日本語

国名：その他
日本人集団における原発性胆汁性胆管炎の感受性、病期分類、症候学的状態、自己免疫性肝炎、肝細胞癌の発症と新規HLA対立遺伝子との関連性(Novel HLA allele associations with susceptibility, staging, symptomatic state, autoimmune hepatitis and hepatocellular carcinoma events for primary biliary cholangitis in the Japanese population)

Khor Seik-Soon, Ueno Kazuko, Nishida Nao, Kawashima Minae, Kawai Yosuke, Aiba Yoshihiro, Hitomi Yuki, Nagasaki Masao, Nakamura Minoru, Tokunaga Katsushi

MHC: Major Histocompatibility Complex 2023年8月 (一社)日本組織適合性学会

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記述言語：英語
日本人の公開可能な長鎖型集団パネル構築とその意義について

長﨑正朗

PacBio ユーザーグループミーティング 2022 2022年5月

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記述言語：日本語会議種別：口頭発表（招待・特別）

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ロングリードシーケンス技術による新規融合遺伝子LILRB3-LILRB5の同定と特徴(Identification and characterization of the novel fusion gene LILRB3-LILRB5 by long-read sequencing technology)

Hirayasu Kouyuki, Khor Seik-Soon, Kawai Yosuke, Hasegawa Gen, Tokunaga Katsushi, Hanayama Rikinari, Nagasaki Masao

日本免疫学会総会・学術集会記録 2023年12月 (NPO)日本免疫学会

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記述言語：英語
ハイブリッドクラウド構築とゲノム情報解析の効率的な運用に関した研究

長﨑正朗

学際大規模情報基盤共同利用・共同研究拠点第 14回シンポジウム 2022年7月

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記述言語：日本語会議種別：口頭発表（一般）

researchmap

▼全件表示

MISC

様々な免疫形質と関連するCD28領域におけるスプライシング制御バリアントの同定

人見祐基, 相葉佳洋, 植野和子, 西田奈央, 河合洋介, 川嶋実苗, 築地信, 岩渕千里, 高田紗奈美, 三宅紀子, 長崎正朗, 徳永勝士, 中村稔, 中村稔

日本人類遺伝学会大会プログラム・抄録集 67th (CD-ROM) 2022年

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J-GLOBAL

researchmap
原発性胆汁性胆管炎(PBC)感受性遺伝子領域を対象とした機能的遺伝子多型(causal variant)の同定

人見祐基, 河合洋介, 植野和子, 西田奈央, 川嶋実苗, 相葉佳洋, 築地信, 長崎正朗, 中村稔, 徳永勝士

2019年9月

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記述言語：日本語
Longitudinal Analysis of Relationships between Individual Fatty Acids and Gestational Diabetes Mellitus in Maternity Log Study.

Satsuki Kumatani, Ochi Daisuke, Yamauchi Takafumi, Tsunemoto Yoshiki, Wagata Maiko, Tanabe Osamu, Minegishi Naoko, Hiyama Satoshi, Nagasaki Masao, Sugawara Junichi

REPRODUCTIVE SCIENCES 2019年3月

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記述言語：英語
Correlation Network Analysis of Maternal Lifelogs and Plasma Metabolites in Maternity Log Study.

Takafumi Yamauchi, Daisuke Ochi, Takahiro Mimori, Yoshiki Tsunemoto, Satsuki Kumatani, Maiko Wagata, Riu Yamashita, Osamu Tanabe, Naoko Minegishi, Nobuo Yaegashi, Satoshi Hiyama, Masao Nagasaki, Junichi Sugawara

REPRODUCTIVE SCIENCES 2019年3月

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記述言語：英語
GWAS and RNA Expression Analysis for Gestational Hypertension using Time-Series Home Blood Pressure Data in Maternity Log Study.

Yoshiki Tsunemoto, Takafumi Yamauchi, Daisuke Ochi, Satsuki Kumatani, Takahiro Mimori, Kaname Kojima, Riu Yamashita, Maiko Wagata, Fumiki Katsuoka, Osamu Tanabe, Naoko Minegishi, Satoshi Hiyama, Masao Nagasaki, Junichi Sugawara

REPRODUCTIVE SCIENCES 2019年3月

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記述言語：英語
Estimating frequency of pathogenic variants in a Japanese population by using the whole-genome reference panel of ToMMo

Yumi Yamaguchi-Kabata, Jun Yasuda, Osamu Tanabe, Yoichi Suzuki, Hiroshi Kawame, Nobuo Fuse, Masao Nagasaki, Yosuke Kawai, Kaname Kojima, Fumiki Katsuoka, Sakae Saito, Inaho Danjoh, Ikuko N. Motoike, Riu Yamashita, Seizo Koshiba, Daisuke Saigusa, Gen Tamiya, Shigeo Kure, Nobuo Yaegashi, Yoshio Kawaguchi, Fuji Nagami, Shinichi Kuriyama, Junichi Sugawara, Naoko Minegishi, Atsushi Hozawa, Soichi Ogishima, Hideyasu Kiyomoto, Takako Takai-Igarashi, Kengo Kinoshita, Masayuki Yamamoto

HUMAN GENOMICS 2018年3月

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記述言語：英語
妊娠高血圧症候群の発症予測に向けた時系列ライフログ解析

山内隆史, 越智大介, 恒元淑希, 和形麻衣子, 原田祐希, 山下理宇, 田邉修, 八重樫伸生, 檜山聡, 長崎正朗, 菅原準一

日本妊娠高血圧学会雑誌 2017年9月

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記述言語：日本語
卵巣明細胞がんを引き起こす遺伝子変異の発見(Discovery of gene alterations causing ovarian clear cell carcinoma)

日本婦人科腫瘍学会雑誌 2017年6月

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記述言語：英語
プライバシ保護ゲノム解析のための秘密計算フィッシャー正確検定の実装評価

長谷川聡, 濱田浩気, 三澤計治, 千田浩司, 荻島創一, 長﨑正朗

マルチメディア，分散協調とモバイルシンポジウム2017論文集 2017年6月

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記述言語：日本語
プライバシ保護ゲノム解析のための秘密計算フィッシャー正確検定の実装評価

長谷川聡, 濱田浩気, 三澤計治, 三澤計治, 千田浩司, 荻島創一, 荻島創一, 長崎正朗, 長崎正朗

情報処理学会シンポジウムシリーズ(CD-ROM) 2017年6月

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記述言語：日本語
Physical Activity and Periodontal Bacteria in Saliva among Japanese Adults

Cong Huang, Riu Yamashita, Yukuto Sato, Haruki Momma, Junko Kawashima, Bin Ye, Shota Sugiyama, Masakazu Nanno, Akito Tsuboi, Masao Nagasaki, Ryoichi Nagatomi

MEDICINE AND SCIENCE IN SPORTS AND EXERCISE 2017年5月

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記述言語：英語

DOI： 10.1249/01.mss.0000519107.55215.92
Genome-wide association study identifies novel susceptibility loci for tanning ability in Japanese population

K. Shido, K. Kojima, A. Hozawa, S. Ogishima, N. Minegishi, Y. Kawai, G. Tamiya, K. Tanno, K. Yamasaki, S. Aiba, Y. Suzuki, M. Nagasaki

JOURNAL OF INVESTIGATIVE DERMATOLOGY 2017年5月

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記述言語：英語
POPULATION-OPTIMIZED SNP ARRAY REVEALS RAP1A AS A NOVEL CANDIDATE SUSCEPTIBILITY GENE FOR CROHN'S DISEASE IN JAPANESE INDIVIDUALS

Yoichi Kakuta, Yosuke Kawai, Takeo Naito, Atsushi Hirano, Junji Umeno, Keiichiro Hiramoto, Masatake Kuroha, Yoshitake Kanazawa, Tomoya Kimura, Katsuya Endo, Yoshitaka Kinouchi, Motohiro Esaki, Masao Nagasaki, Tooru Shimosegawa

GASTROENTEROLOGY 2017年4月

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記述言語：英語
DICHOTOMOUS EFFECTS OF ATG16L1 AND LRRK2 IN MODULATING PANETH CELL DEFECT IN JAPANESE AND NORTH AMERICAN CROHN'S DISEASE PATIENTS

Ta-Chiang Liu, Takeo Naito, Zhenqiu Liu, Kelli VanDussen, Talin Haritunians, Dalin Li, Katsuya Endo, Yosuke Kawai, Masao Nagasaki, Yoshitaka Kinouchi, Dermot McGovern, Tooru Shimosegawa, Yoichi Kakuta, Thaddeus S. Stappenbeck

GASTROENTEROLOGY 2017年4月

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記述言語：英語
早発型発達緑内障における原因遺伝子の探索

布施昇男, 木村雅恵, 清水愛, 河合洋介, 小島要, 長崎正朗, 濱中輝彦, 石田誠夫, 中村誠, 酒井寛, 池田陽子, 森和彦, 中澤徹, 勝岡史城, 安田純, 山本雅之

日本眼科学会雑誌 2017年3月

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記述言語：日本語
Identification of Somatic Genetic Alterations in Ovarian Clear Cell Carcinomas with Next Generation Sequencing.

Yusuke Shibuya, Sakae Saito, Kaname Kojima, Bin Li, Hideki Tokunaga, Masao Nagasaki, Jun Yasuda, Nobuo Yaegashi

REPRODUCTIVE SCIENCES 2017年3月

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記述言語：英語
次世代シークエンサーを用いた卵巣明細胞腺癌の遺伝子変異の探索

渋谷祐介, 齋藤さかえ, 小島要, 李賓, 徳永英樹, 長崎正朗, 安田純, 八重樫伸生

日本癌学会総会記事 2016年10月

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記述言語：英語
マルチオミクスが解き明かす疾患生物学日本人多層オミックス参照パネルの拡張

小柴生造, 三枝大輔, 元池育子, 小島要, 城田松之, 齋藤智, 勝岡史城, 河合洋介, 山口由美, 田邉修, 長崎正郎, 安田純, 木下賢吾, 山本雅之

日本生化学会大会プログラム・講演要旨集 2016年9月

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記述言語：日本語
秘密計算フィッシャー正確検定(1)標本数が少ない場合 (情報セキュリティ)

千田浩司, 長谷川聡, 濱田浩気, 荻島創一, 三澤計治, 長﨑正朗

電子情報通信学会技術研究報告 = IEICE technical report : 信学技報 2016年7月

　詳細を見る

記述言語：日本語
プライバシ保護ゲノム解析のための秘密計算フィッシャー正確検定 (情報セキュリティ)

長谷川聡, 濱田浩気, 千田浩司, 荻島創一, 三澤計治, 長﨑正朗

電子情報通信学会技術研究報告 = IEICE technical report : 信学技報 2016年7月

　詳細を見る

記述言語：日本語
秘密計算フィッシャー正確検定(2)標本数が多い場合 (情報セキュリティ)

濱田浩気, 長谷川聡, 千田浩司, 荻島創一, 三澤計治, 長崎正朗

電子情報通信学会技術研究報告 = IEICE technical report : 信学技報 2016年7月

　詳細を見る

記述言語：日本語
卵巣明細胞腺癌を引き起こす遺伝子変異の発見(Discovery of gene alterations causing ovarian clear cell carcinoma)

渋谷祐介, 徳永英樹, 安田純, 長崎正朗, 斎藤さかえ, 小島要, 李賓, 八重樫伸生

日本婦人科腫瘍学会雑誌 2016年6月

　詳細を見る

記述言語：英語
Estimation of allele frequency of pathological variants based on whole-genome sequencing of 1070 Japanese individuals

Yumi Yamaguchi-Kabata, Yosuke Kawai, Kaname Kojima, Naoki Nariai, Takahiro Mimori, Yukuto Sato, Fumiki Katsuoka, Jun Yasuda, Masayuki Yamamoto, Masao Nagasaki

GENES & GENETIC SYSTEMS 2015年12月

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記述言語：英語
日本人全ゲノムファレンスパネルの構築と今後

長崎正朗, 安田純, 勝岡史城, 成相直樹, 小島要, 河合洋介, 山口由美, 横澤潤二, 檀上稲穂, 齊藤さかえ, 佐藤行人, 三森隆弘, 津田薫, 齊藤るみ子, PAN Xiaoquing, 西川聡, 伊藤信, 黒木陽子, 田邉修, 布施昇男, 栗山進一, 清元秀泰, 寶澤篤

日本遺伝学会大会プログラム・予稿集 2015年9月

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記述言語：日本語
SUGAR: graphical user interface-based high-resolution data cleaning tool for high-throughput sequencing data

Yukuto Sato, Kaname Kojima, Naoki Nariai, Yumi Yamaguchi-Kabata, Yosuke Kawai, Masao Nagasaki

GENES & GENETIC SYSTEMS 2014年12月

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記述言語：英語
Construction of Japanese Whole Genome Information and Data Analysis in Tohoku Medical Megabank Organization

Masao Nagasaki

GENES & GENETIC SYSTEMS 2014年12月

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記述言語：英語
Nonparametric inference of population demography from SNP data

Yosuke Kawai, Yukuto Sato, Yumi Yamaguchi, Naoki Nariai, Sachiyo Sugimoto, Takahiro Mimori, Kaname Kojima, Masao Nagasaki

GENES & GENETIC SYSTEMS 2014年12月

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記述言語：英語
食道扁平上皮癌でのBAP1遺伝子変異によるGIS期移行異常(BAP1 mutation somatically occurring in a human esophageal squamous cell carcinoma abrogates G1-S transition)

森隆弘, 住井真紀子, 斎木由利子, 長崎正朗, 千葉奈津子, 石岡千加史

日本癌学会総会記事 2014年9月

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記述言語：英語
IDENTIFICATION OF ACQUIRED MUTATIONS BY WHOLE-GENOME SEQUENCING IN MONOMAC SYNDROME EVOLVING INTO MYELODYSPLASIA AND ACUTE LEUKEMIA

T. Fujiwara, N. Fukuhara, R. Funayama, N. Nariai, M. Kamata, T. Nagashima, K. Kojima, Y. Onishi, Y. Sasahara, K. Ishizawa, M. Nagasaki, K. Nakayama, H. Harigae

HAEMATOLOGICA 2014年6月

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記述言語：英語
腎疾患個別化医療実現に向けた健常人ゲノムコホートの構築

清元秀泰, 阿部倫昭, 奥田拓史, 岡村将史, 宮崎真理子, 寳澤篤, 栗山進一, 高井貴子, 長崎正朗, 峯岸直子, 安田純, 森建文, 中谷純, 菅原準一, 八重樫伸生, 佐藤博, 山本雅之, 伊藤貞嘉

日本腎臓学会誌 2014年5月

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記述言語：日本語
眼疾患と遺伝子緑内障のゲノム解析次世代医療・個別化医療に向けて

布施昇男, 清水愛, 木村雅恵, 高野良真, 石棟, 宮澤晃子, 国松志保, 劉孟林, 渡邉亮, 安田正幸, 横山悠, 檜森紀子, 津田聡, 山本耕太郎, 中澤徹, 安田純, 勝岡史城, 小島要, 成相直樹, 松本光代, 元池育子, 長崎正朗, 木下賢吾, 五十嵐和彦, 山本雅之, 新堀哲也, 青木洋子, 松原洋一, 舟山亮, 長嶋剛史, 中山啓子, 眞島行彦, 船山智代, 田中光一, 原田高幸, 阿部春樹, 福地健郎, 安田典子, 出田秀尚, 鄭暁東, 白石敦, 大橋裕一, 石田誠夫, 原岳, 金森章泰, 山田裕子, 中村誠, 酒井寛, Richards Julia E

日本眼科学会雑誌 2014年3月

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記述言語：日本語

主に1990年代から始まった遺伝要因が発症に関係する疾患の解析は,単一遺伝子疾患や遺伝子変異(mutation)から多因子疾患の感受性因子である遺伝子多型(variation)へと移行してきた.個人ゲノムの解析が進むにつれて,個々人の間にはゲノム全体で数百万ヶ所の塩基配列が異なることが判明している.この塩基配列の相違が頻度の高い疾患(common disease)の発症に関わっていることが証明されてきた.近年ゲノム全体にわたる一塩基多型(single nucleotide polymorphism:SNP)を用いた相関解析(genome-wide association study:GWAS)が盛んに行われてきているが,高頻度の多型(common variant)はその病気への寄与が比較的小さいことから,臨床研究をより精度の高いものにするためには,common variantに加えて,病気への寄与度が大きい低頻度の多型(rare variant)の解析も行うことが必要である.さらにゲノム情報を用いた次世代医療,個別化医療に向け,種々の表現型(endophenotype)との関連を調べることは重要である.本研究において,我々は緑内障の病態解明をゲノム解析の観点から検討した.現在まで緑内障原因遺伝子は数種類同定されているが,当初はメンデル遺伝性の家系解析からの同定が主であった.2007年,GWASによって,LOXL1遺伝子の多型と【嚢】性緑内障が関連すると報告され,我々を含む多施設で追試された.それ以降,SNPを用いた相関解析が主流となってきており,原発開放隅角緑内障(primary open-angle glaucoma:POAG),正常眼圧緑内障(normal-tension glaucoma:NTG)に関連した遺伝子としてCDKN2B-AS1遺伝子などが発表された.また我々は,緑内障GLC1B遺伝子座が存在する常染色体2番上において,SNPを用いた相関解析により,Hexokinase 2(HK2)遺伝子多型rs678350がPOAG,NTGに関連していることを明らかにし,NCK2遺伝子多型rs2033008がNTGに関連していることを示した.マウスを用いてHk2,Nck2蛋白質の免疫組織染色を行った結果,神経節細胞に発現がみられ,緑内障の病態に関連していると考えられた.近年,遺伝子解析は,マーカーを用いた相関解析から次世代シークエンサーを用いた網羅的な解析へと移行してきている.その中でも,全エクソン解析(エクソーム解析)は,約20万個のエクソンをすべて解析するものである.これを発達緑内障早発型の解析に用いた.発達緑内障早発型では,CYP1B1遺伝子が唯一発見されている原因遺伝子であるが,新規原因遺伝子解析のために,今回次世代シークエンサーでの解析に適する症例・家系の収集を行い,エクソーム解析を行った.CYP1B1遺伝子スクリーニングの後,CYP1B1遺伝子変異陰性の症例を用い,エクソーム解析を行った.その結果,発達緑内障早発型では原因遺伝子について遺伝的異質性が高いこと,de novo変異も原因の候補であることを明らかにした.次に,POAGおよびNTGにおける新規原因遺伝子解明のため,POAG1家系,NTG2家系のエクソーム解析を行った.1000 Genomes,SNPデータベースでフィルターをかけ,各々数十個～100個候補遺伝子を抽出した.今回の3家系に共通している候補遺伝子はなく,2家系においては神経系の細胞の分化に関連する転写因子とアクチン関連分子が候補遺伝子であった.また,一般の孤発例にも適用を開始し,この手法は緑内障原因遺伝子の探索に有用と考えられた.ゲノム情報を活用しゲノム医療を現実にするためには,遺伝子,環境,病気の3つの因果関係を明らかにしていかなければならない.今回,東北大学東北メディカル・メガバンクにおいて大規模バイオバンクを構築し,集積される生体試料から疾患と関連する遺伝子の同定と,それらのバイオマーカーの探索を開始した.2013年度中に1,000人(深度30倍以上)の全ゲノム配列解析を実施し,日本人ゲノムのSNPを頻度0.5%以下まで決定して日本人標準ゲノムリファレンスパネルを作成し,疾患感受性と関連する遺伝子を同定する.解析により同定した多型の中から日本人特有のもの,関連遺伝子を抽出し,日本人に最適化した緑内障SNPアレイを開発する.ゲノム情報と健康情報・診療情報とを集約することで,緑内障の予防や診断精度の向上,治療効果の向上のための緑内障個別化医療の実現を目指すことが可能になると期待される.(著者抄録)
The Activation of the Wnt3a/beta-Catenin Pathway Induced Maturation of Impaired Neutrophils as Well as the Endoplasmic Reticulum Stress in Induced Pluripotent Stem Cell Derived from a Severe Congenital Neutropenia Patient with ELANE Mutation

Takafumi Hiramoto, Yasuhiro Ebihara, Yoko Mizoguchi, Kazuhiro Nakamura, Kiyoshi Yamaguchi, Kazuko Ueno, Naoki Nariai, Shinji Mochizuki, Shohei Yamamoto, Masao Nagasaki, Yoichi Furukawa, Kenzaburo Tani, Hiromitsu Nakauchi, Masao Kobayashi, Kohichiro Tsuji

MOLECULAR THERAPY 2013年6月

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記述言語：英語
Recurrent Mutations of Multiple Components of Cohesin Complex in Myeloid Neoplasms

Ayana Kon, Lee-Yung Shih, Masashi Minamino, Masashi Sanada, Yuichi Shiraishi, Yasunobu Nagata, Kenichi Yoshida, Yusuke Okuno, Masashige Bando, Shumpei Ishikawa, Aiko Sato-Otsubo, Genta Nagae, Claudia Haferlach, Daniel Nowak, Yusuke Sato, Tamara Alpermann, Masao Nagasaki, Teppei Shimamura, Hiroko Tanaka, Kenichi Chiba, Ryo Yamamoto, Tomoyuki Yamaguchi, Makoto Otsu, Naoshi Obara, Mamiko Sakata-Yanagimoto, Tsuyoshi Nakamaki, Ken Ishiyama, Florian Nolte, Wolf-Karsten Hofmann, Shuichi Miyawaki, Shigeru Chiba, Hiraku Mori, Hiromitsu Nakauchi, H. Phillip Koeffler, Hiroyuki Aburatani, Torsten Haferlach, Katsuhiko Shirahige, Satoru Miyano, Seishi Ogawa

BLOOD 2012年11月

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記述言語：英語

DOI： 10.1182/blood.V120.21.782.782
Mutations of cohesin genes in myeloid malignancy

Ayana Kon, Masashi Sanada, Kenichi Yoshida, Yuichi Shiraishi, Yasunobu Nagata, Yusuke Sato, Aiko Sato-Otsubo, Masao Nagasaki, Naoshi Obara, Mamiko Sakata-Yanagimoto, Ken Ishiyama, Hiraku Mori, Shuichi Miyawaki, H. Phillip Koeffler, Lee-Yung Shih, Shigeru Chiba, Satoru Miyano, Seishi Ogawa

CANCER RESEARCH 2012年4月

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記述言語：英語

DOI： 10.1158/1538-7445.AM2012-5117
EGF receptor tyrosine kinase defines critical prognostic genes of stage IA lung adenocarcinoma

Asuka Nakata, Mai Yamauchi, Rui Yamaguchi, Takashi Kohno, Masao Nagasaki, Teppei Shimamura, Seiya Imoto, Ayumu Saito, Kazuko Ueno, Yousuke Hatanaka, Ryo Yoshida, Tomoyuki Higuchi, Masaharu Nomura, David G. Beer, Jun Yokota, Satoru Miyano, Noriko Gotoh

CANCER RESEARCH 2012年4月

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記述言語：英語

DOI： 10.1158/1538-7445.AM2012-LB-99
Frequent splicing pathway mutations and aberrant RNA splicing in myelodysplasia

Kenichi Yoshida, Masashi Sanada, Yuichi Shiraishi, Daniel Nowak, Yasunobu Nagata, Ryo Yamamoto, Yusuke Sato, Aiko Sato-Otsubo, Ayana Kon, Masao Nagasaki, George Chalkidis, Yutaka Suzuki, Masashi Shiosaka, Ryoichiro Kawahata, Tomoyuki Yamaguchi, Makoto Otsu, Naoshi Obara, Mamiko Sakata-Yanagimoto, Ken Ishiyama, Hiraku Mori, Florian Nolte, Wolf-Karsten Hofmann, Shuichi Miyawaki, Sumio Sugano, Claudia Haferlach, H. Phillip Koeffler, Lee-Yung Shih, Torsten Haferlach, Shigeru Chiba, Hiromitsu Nakauchi, Satoru Miyano, Seishi Ogawa

CANCER RESEARCH 2012年4月

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記述言語：英語

DOI： 10.1158/1538-7445.AM2012-5119
ダウン症候群に合併した一過性骨髄増殖症(TAM)および急性巨核芽球性白血病(AMKL)の全エクソンシーケンス

吉田健一, 土岐力, 朴明子, 永田安伸, 王汝南, 白石友一, 真田昌, 昆彩菜, 佐藤亜衣子, 長崎正朗, 宮野悟, 金兼弘和, 川上清, 加藤剛二, 小島勢二, 林泰秀, 伊藤悦朗, 小川誠司

小児がん 2011年11月

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記述言語：日本語
Frequent Pathway Mutations of Splicing Machinery in Myelodysplasia

Kenichi Yoshida, Masashi Sanada, Yuichi Shiraishi, Daniel Nowak, Yasunobu Nagata, Ryo Yamamoto, Yusuke Sato, Aiko Sato-Otsubo, Ayana Kon, Masao Nagasaki, George Chalkidis, Yutaka Suzuki, Makoto Otsu, Naoshi Obara, Mamiko Sakata-Yanagimoto, Ken Ishiyama, Hiraku Mori, Florian Nolte, Wolf-Karsten Hofmann, Shuichi Miyawaki, Sumio Sugano, Claudia Haferlach, H. Phillip Koeffler, Lee-Yung Shih, Torsten Haferlach, Shigeru Chiba, Hiromitsu Nakauchi, Satoru Miyano, Seishi Ogawa

BLOOD 2011年11月

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記述言語：英語
Functional Analysis of SRSF2 Mutations in Myelodysplastic Syndromes and Related Disorders

Ayana Kon, Masashi Sanada, Kenichi Yoshida, Yasunobu Nagata, Yuichi Shiraishi, Yusuke Sato, Aiko Sato-Otsubo, Ryo Yamamoto, Masao Nagasaki, Yutaka Suzuki, Tomoyuki Yamaguchi, Makoto Otsu, Sumio Sugano, Shigeru Chiba, H. Phillip Koeffler, Lee-Yung Shih, Hiromitsu Nakauchi, Satoru Miyano, Seishi Ogawa

BLOOD 2011年11月

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記述言語：英語
Mutational Spectrum Analysis of Interesting Correlation and Interrelationship Between RNA Splicing Pathway and Commonly Targeted Genes in Myelodysplastic Syndrome

Yasunobu Nagata, Masashi Sanada, Ayana Kon, Kenichi Yoshida, Yuichi Shiraishi, Aiko Sato-Otsubo, Hiraku Mori, Ken Ishiyama, Mamiko Sakata-Yanagimoto, Naoshi Obara, Masao Nagasaki, Shuichi Miyawaki, Shigeru Chiba, Satoru Miyano, Shih Lee Yung, H. Phillip Koeffler, Seishi Ogawa

BLOOD 2011年11月

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記述言語：英語

DOI： 10.1182/blood.V118.21.273.273
ウイルス性肝細胞がんの全ゲノムシークエンス解析(Whole Genome Sequencing and Analysis of Virus-related Hepatocellular Carcinoma)

中川英刀, 藤本明洋, 角田達彦, 長崎正朗, 柴田龍弘, 十時泰, 上野昌樹, 川上由育, 山田晃正, 茶山一彰, 山上裕機, 宮野悟, 中村祐輔

日本癌学会総会記事 2011年9月

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記述言語：英語
心筋細胞におけるグルココルチコイド受容体の役割の解明

丸山崇子, 吉川賢忠, 長崎正朗, 井元清哉, 宮野悟, 徳留さとり, 佐野元昭, 福田恵一, 清水宣明, 森本幾夫, 田中廣壽

日本生化学会大会・日本分子生物学会年会合同大会講演要旨集 2010年12月

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記述言語：日本語
生命をシステムとして理解するための計算戦略 : Cell Illustrator の開発

長崎正朗, 斉藤あゆむ, 宮野悟

計測と制御 = Journal of the Society of Instrument and Control Engineers 2010年8月

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記述言語：日本語
Critical prognostic genes for stage I lung cancer are identified from normal growth factor-regulated gene network by overcoming cancer heterogeneity

Noriko Gotoh, Mai Yamauchi, Rui Yamauchi, Masao Nagasaki, Teppei Shimamura, Seiya Imoto, Ayumu Saito, Kazuko Ueno, Yousuke Hatanaka, Ryo Yoshida, Tomoyuki Higuchi, Masaharu Nomura, Takashi Kohno, Jun Yokota, David G. Beer, Satoru Miyano

CANCER RESEARCH 2010年4月

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記述言語：英語

DOI： 10.1158/1538-7445.AM10-LB-132
Ligand-based gene expression profiling reveals novel roles of glucocorticoid receptor in the cardiomyocytes

Noritada Yoshikawa, Motoaki Sano, Satori Tokudome, Noriaki Shimizu, Takako Maruyama, Masao Nagasaki, Seiya Imoto, Satoru Miyano, Yusuke Tagata, Shinobu Nishitani, Kenji Takehana, Keiichi Fukuda, Chikao Morimoto, Hirotoshi Tanaka

ENDOCRINE JOURNAL 2010年3月

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記述言語：英語
Identification of new biomarkers and molecular targets of lung cancers by systems biology approach

Mai Yamauchi, Rui Yamaguchi, Masao Nagasaki, Teppei Shimamura, Seiya Imoto, Ayumu Saito, Kazuko Ueno, Yousuke Hatanaka, Ryo Yoshida, Kazuyuki Okeguchi, Takashi Kohno, Jun Yokota, Satoru Miyano, Noriko Gotoh

CANCER RESEARCH 2009年5月

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記述言語：英語
動的ネットワーク構造探索の計算イニシアティブバイオマーカー・分子標的探索のための動的ネットワークを予測する計算科学的方法の開発

井元清哉, 山口類, 島村徹平, 玉田嘉紀, 長崎正朗, 斉藤あゆむ, 植野和子, 畑中洋亮, 吉田亮, 樋口知之, 山内麻衣, 後藤典子, 宮野悟

日本生化学会大会・日本分子生物学会年会合同大会講演要旨集 2008年11月

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記述言語：日本語
グルココルチコイド心筋細胞におけるグルココルチコイド受容体標的遺伝子の解明

吉川賢忠, 長崎正朗, 井元清哉, 宮野悟, 徳留さとり, 佐野元昭, 福田恵一, 清水宣明, 森本幾夫, 田中廣壽

日本内分泌学会雑誌 2008年9月

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記述言語：日本語
ペトリネットによる転写制御ネットワークのモデリングと統計的推測

吉田亮, 長崎正郎, 山口類, 井元清哉, 宮野悟, 樋口知之

情報処理学会研究報告. BIO, バイオ情報学 2008年6月

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記述言語：その他
ダイナミックパスウェイモデリング言語:CSML (ゲノムから生命システムへ) -- (ゲノムから情報科学)

長崎正朗, 土井淳, 宮野悟

蛋白質核酸酵素 2005年12月

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記述言語：日本語
Java RMI による Genomic Object Net の分散オブジェクト化(バイオエンジニアリングI)

河野智一, 北風裕教, 長崎正朗, 土井淳, 松野浩嗣, 宮野悟

講演論文集 2004年3月

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記述言語：日本語
An intronic SNP in a RUNX1 binding site of SLC22A4, encoding an organic cation transporter, is associated with rheumatoid arthritis

S Tokuhiro, R Yamada, XT Chang, A Suzuki, Y Kochi, T Sawada, M Suzuki, M Nagasaki, M Ohtsuki, M Ono, H Furukawa, M Nagashima, S Yoshino, A Mabuchi, A Sekine, S Saito, A Takahashi, T Tsunoda, Y Nakamura, K Yamamoto

NATURE GENETICS 2003年12月

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記述言語：英語

DOI： 10.1038/ng1267

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所属学協会

日本バイオインフォマティクス学会
日本がん学会
日本人類遺伝学会

担当授業科目

生命医科学Ⅰ

2024年4月 - 2024年6月春学期
Medical Life Sciences Ⅰ

2024年4月 - 2024年6月春学期
生命医科学Ⅰ

2024年4月 - 2024年6月春学期
Medical Life Sciences Ⅰ

2024年4月 - 2024年6月春学期

社会貢献・国際連携活動概要

産学連携活動の１つとして「量子計算技術を中心としたゲノム情報解析の応用に関する研究」の共同研究を開始した。

社会貢献活動

研究題目：ネットワーク統計技術とAIの融合によるバイオメディカル大規模解析技術開発とその応用に関する研究ネットワークAI統計部門の設立と運用を開始した。

民間機関等：株式会社BlueMeme 2023年10月

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対象：社会人・一般,　学術団体,　企業,　市民団体,　行政機関

種別：その他