The genome is a blueprint of humans. The goal of our team is to deci-27pher the blueprint and elucidate hidden biology. We focus on large-scale human genome, omics, and phenome data and the underlying high-dimen-sional network. By developing novel methodologies in statistical genetics and machine learning, we redefine human biology as systems of genetics. Our team aims to elucidate disease biology, leading to novel drug discovery and imple-mentation of genomic personalized medicine.In 2021, our team conducted a series of large-scale human genomics studies by utilizing newly developed computational methodologies. Cross-population genome-wide association study (GWAS) meta-analysis integrating global bio-banks (Biobank Japan, UK Biobank and FinnGen) identified thousands of ge-netic variants associated with a wide range of human phenotypes. Deconvolu-tion of the phenome-wide GWAS summary statistics using Truncated Singular Value Decomposition (TSVD) revealed the hidden biology of human complex diseases (Sakaue S and Kanai M et al. Nat Genet 2021).The microbiome is the genetic material of all the microbes that live on and inside the human body and plays essential roles in a variety of human diseases. As exploitation of new human omics layers, we developed in silico pipelines to quantify the entire human gut virome. Based on the shotgun sequencing of 476 Japanese, we conducted a case-control comparison of viral abundance in mul-tiple autoimmune diseases. We found that crAss-like phages, one of the main components of a healthy gut virome, were significantly decreased in the gut of patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). A quantitative virus-bacterium association analysis identified symbiosis between Podoviridae and Faecalibacterium. Our study suggested that the gut vi-rome can affect our body either directly or via bacteria and presented new can-didates that contribute to the development of autoimmune diseases (Tomofuji Y et al. Ann Rheum Dis 2022).Figure: Whole gut virome analysis of autoim-mune diseasesWe constructed in silico pipelines to quantify the hu-man gut virome from metagenome shotgun sequenc-ing data. Application of the pipeline to the shotgun sequencing of 476 Japanese identified novel features of the gut virome in autoimmune diseases, including decreased crAss-like phages in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE).Recent Major PublicationsTomofuji Y, Kishikawa T, Maeda Y, Ogawa K, Nii T, Okuno T, Oguro-Igashira E, Kinoshita M, Yamamoto K, Sonehara K, Yagita M, Hosokawa A, Motooka D, Matsumoto Y, Matsuoka H, Yoshimura M, Ohshima S, Nakamura S, Inohara H, Mochizuki H, Takeda K, Kumanogoh A, Okada Y. Whole gut virome analysis of 476 Japanese revealed a link between phage and autoimmune disease. Ann Rheum Dis 81, 278-288 (2022)Okada Y, Wang QS. A massive effort links protein-coding gene variants to health. Nature 599, 561-563 (2021)Sakaue S, Kanai M, Tanigawa Y, Karjalainen J, Kurki M, Koshiba S, Narita A, Konuma T, Yamamoto K, Akiyama M, Ishigaki K, Suzuki A, Suzuki K, Obara W, Yamaji K, Taka-hashi K, Asai S, Takahashi Y, Suzuki T, Shinozaki N, Yama-guchi H, Minami S, Murayama S, Yoshimori K, Nagayama S, Obata D, Higashiyama M, Masumoto A, Koretsune Y; FinnGen, Ito K, Terao C, Yamauchi T, Komuro I, Kadowaki T, Tamiya G, Yamamoto M, Nakamura Y, Kubo M, Mu-rakami Y, Yamamoto K, Kamatani Y, Palotie A, Rivas MA, Daly MJ, Matsuda K, Okada Y. A cross-population atlas of genetic associations for 220 human phenotypes. Nat Genet 53, 1415-1424 (2021)Invited presentationsOkada Y. “Statistical genetics, disease biology, drug discovery, and personalized medicine” The 50th Annual Meeting of The Japanese Society for Immunology (Nara, Japan) November 2021Okada Y. “Big data analysis of autoimmune diseases” 41st Annual Scientific Meeting of Korean College of Rheumatology 2021 (Seoul, Korea/Online) October 2021Okada Y. “Cross-population Mendelian randomization analysis and application for novel drug discovery” Mendelian Randomization Conference 2021 (Bristol, England/Online) July 2021Okada Y. “Drug discovery through genomic analysis” The 65th Annual General Assembly and Scientific Meeting of the Japan College of Rheumatology (Kobe, Japan) April 2021Okada Y. “Statistical genetics, disease biology, and drug discovery” Complex Disease Genetics Day 2021 (Helsinki, Finland/Online) January 2021Laboratory for Systems GeneticsTeam Leader: Yukinori Okada
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