Lab Activities

Laboratory for Systems Genetics

Research Activities

Yukinori Okada portrait

Team Director

Yukinori Okada

The genome is the human blueprint. Our goal is to decipher the blueprint and elucidate its hidden biology. An individual’s genetic background has impacts on disease risk. Using statistical and bioinformatics approaches, Systems Genetics evaluates the causality of genetic variations on phenotypes. Namely, the development of the methodology to integrate large-scale human genomics data with diverse biological and clinical information. We focus on large-scale human genome, omics and phenome data and the underlying high-dimensional network. With novel bioinformatics methodologies, we redefine human biology as systems genetics. Our team aims to elucidate disease biology and contribute to novel drug discovery and implementation of personalized genomic medicine.

We have advanced the study of clonal hematopoiesis (CH) by integrating somatic mutation data into single-cell multi-omics to elucidate biological impacts of CH on human immune-related diseases. We constructed a Japanese single-cell immune atlas of over 1.5 million cells (OASIS), and established a framework to project somatic alterations—including mosaic chromosomal alterations (mCAs), loss of Y (LOY), and mtDNA mutations—onto single-cell profiles (Edahiro R. Nat Genet 2025). This enabled the identification of mutation and cell type-specific immunological features. Applying this framework, we elucidated the interplay between germline variants and mCAs in COVID-19 vaccination responses (Sonehara K. Cell Genom 2025). Furthermore, in neuromyelitis optica spectrum disorder (NMOSD), we discovered that a somatic 21q deletion specifically observed in CD4+ T cells dysregulates the type I interferon pathway (Yata T. Cell Genom 2025). These studies demonstrate that projecting somatic genetic information onto single-cell dynamics is an essential paradigm for understanding immune diseases and realizing personalized medicine.

A multiomic immune cell atlas, the Osaka Atlas of Immune Cells (OASIS)

Laboratory for Systems Genetics figure

A multiomic immune cell atlas, the Osaka Atlas of Immune Cells (OASIS)

Laboratory for Systems Genetics figure

Recent Major Publications

  1. Edahiro R, Sato G, Naito T, Shirai Y, Saiki R, Sonehara K, Tomofuji Y, Yamamoto K, Namba S, Sasa N, Nagao G, Wang QS, Takahashi Y, Hasegawa T, Kishikawa T, Suzuki K, Liu Y, Motooka D, Takuwa A, Tanaka H, Azekawa S, Namkoong H, Koike R, Kimura A, Imoto S, Miyano S, Kanai T, Fukunaga K, Uemura M, Morita T, Kato Y, Hirata H, Takeda Y, Doki Y, Eguchi H, Okuzaki D, Sakakibara S, Ogawa S, Kumanogoh A, Okada Y. Deciphering state-dependent immune features from multi-layer omics data at single-cell resolution. Nat Genet 57, 1905–1921 (2025)

  2. Sasa N, Kojima S, Koide R, Hasegawa T, Namkoong H, Hirota T, Watanabe R, Nakamura Y, Oguro-Igashira E, Ogawa K, Yata T, Sonehara K, Yamamoto K, Kishikawa T, Sakaue S, Edahiro R, Shirai Y, Maeda Y, Nii T, Chubachi S, Tanaka H, Yabukami H, Suzuki A, Nakajima K, Arase N, Okamoto T, Nishikawa R, Namba S, Naito T, Miyagawa I, Tanaka H, Ueno M, Ishitsuka Y, Furuta J, Kunimoto K, Kajihara I, Fukushima S, Miyachi H, Matsue H, Kamata M, Momose M, Bito T, Nagai H, Ikeda T, Horikawa T, Adachi A, Matsubara T, Ikumi K, ..., Kanai T, Morita A, Matsuda F, Tamari M, Kumanogoh A, Tanaka Y, Ohmura K, Fukunaga K, Imoto S, Miyano S, Parrish NF, Okada Y. Blood DNA virome associates with autoimmune diseases and COVID-19. Nat Genet 57, 65–79 (2025)

  3. Sonehara K, Watanabe R, Matsumura Y, Mitsui Y, Ogawa Y, Odomari K, Sakaue S, Namba S, Komuro M, Edamoto M, Watanabe J, Hirota T, Arase N, Nakamura Y, Nakajima K, Okamoto T, Nishikawa R, Yamamoto K, Suzuki K, Kishikawa T, Edahiro R, Shirai Y, Naito T, Sasa N, Ishitsuka Y, Furuta J, Kunimoto K, Kajihara I, Fukushima S, Miyachi H, Matsue H, Kamata M, Momose M, Miyagawa I, Tanaka H, Ueno M, Bito T, Nagai H, Ikeda T, Horikawa T, Adachi A, Matsubara T, Nishida E, Project BJ, Matsuda K, Shojima N, Nakagawa I, Asano Y, Sato S, Imafuku S, Tada Y, Nishigori C, Jinnin M, Ihn H, Asahina A, Saeki H, Yamauchi T, Kadowaki T, ..., Tamari M, Satoh T, Fujimoto M, Morita A, Okada Y. Whole-genome sequencing reveals rare and structural variants contributing to psoriasis and identifies CERCAM as a risk gene. Cell Genom 5, 100978 (2025)

  4. Yamamoto Y, Shirai Y, Sonehara K, Namba S, Ojima T, Yamamoto K, Edahiro R, Suzuki K, Kanai A, Oda Y, Suzuki Y, Morisaki T, Narita A, Takeda Y, Tamiya G, Yamamoto M, Matsuda K, Kumanogoh A, Yamauchi T, Kadowaki T, Okada Y. Dissecting cross-population polygenic heterogeneity across respiratory and cardiometabolic diseases. Nat Commun 16, 3765 (2025)

  5. Smit RA, Wade KH, Hui Q, Arias JD, Yin X, Christiansen MR, Yengo L, Preuss MH, Nakabuye M, Rocheleau G, Graham SE, Buchanan VL, Chittoor G, Graff M, Guindo-Martinez M, Lu Y, Marouli E, Sakaue S, Spracklen CN, Vedantam S, Wilson EP, Chen S, Ferreira T, Ji Y, Karaderi T, Luell K, Machado M, Malden DE, Medina-Gomez C, Moore A, Rueeger S, Akiyama M, Allison MA, Alvarez M, Andersen MK, Appadurai V, Arbeeva L, Bartell E, Bhaskar S, Bielak LF, Bis JC, Bollepalli S, Bork-Jensen J, Bradfield JP, Bradford Y, Brandl C, Braund PS, Brody JA, Broeckel U, Burgdorf KS, Cade BE, Cai Q, Camarda S, Campbell A, Canadas-Garre M, Chai J, Chesi A, ..., Okada Y, Willer CJ, Young KL, Fatumo S, McCaffery JM, Timpson NJ, Hirschhorn JN, Sun YV, Berndt SI, Loos RJ. Polygenic prediction of body mass index and obesity through the life course and across ancestries. Nat Med 31, 3151–3168 (2025)

  6. Kock K, Tan L, Han K, Ando Y, Jevapatarakul D, Chatterjee A, Lin Q, Buyamin E, Sonthalia R, Rajagopalan D, Tomofuji Y, Sankaran S, Park M, Abe M, Chantaraamporn J, Furukawa S, Ghosh S, Inoue G, Kojima M, Kouno T, Lim J, Myouzen K, Nguantad S, Oh J, Rayan N, Sarkar S, Suzuki A, Thungsatianpun N, Venkatesh P, Moody J, Nakano M, Chen Z, Tian C, Zhang Y, Tong Y, Tan C, Tizazu A, Loh M, Hwang Y, Ho RC, Larbi A, Ng T, Won H, Wright FA, Villani A, Park J, Choi M, Liu B, Maitra A, Pithukpakorn M, Suktitipat B, Ishigaki K, Okada Y, Yamamoto K, Carninci P, Chambers JC, Hon C, Matangkasombut P, Charoensawan V, Majumder PP, Shin JW, Park W, Prabhakar S. Asian diversity in human immune cells. Cell 188, 2288-2306.e24 (2025)

  7. Takahashi Y, Wang QS, Hasegawa T, Namkoong H, Inoue F, Fukunaga K, Imoto S, Miyano S, Okada Y. JOB: Japan Omics Browser provides integrative visualization of multi-omics data. BMC Genomics 26, 451 (2025)

  8. Li B, Sakaguchi T, Tani H, Ito T, Murakami M, Okumura R, Kobayashi M, Okuzaki D, Motooka D, Ikeuchi H, Ogino T, Mizushima T, Hirota S, Otake-Kasamoto Y, Kishikawa T, Nakamura S, Kobiyama K, Ishii KJ, Hashiguchi T, Kawai T, Kuroda E, Shinzaki S, Ise W, Kurosaki T, Kikuchi A, Tomofuji Y, Okada Y, Takeda K, Kayama H. OTUD3 prevents ulcerative colitis by inhibiting microbiota-mediated STING activation. Sci Immunol 10, eadm6843 (2025)

  9. Rowntree LC, Allen LF, Hagen RR, McQuilten HA, Quadeer AA, Chaurasia P, Kaewpreedee P, Lee KW, Cohen CA, Petersen J, Littler DR, Habel JR, Zhang W, Cheng SM, Chan KK, Kwok JS, Leung KS, Wu JT, Lee C, Davies J, Pannaraj PS, Allen EK, Thomas PG, Tosif S, Crawford NW, Lappas M, Thevarajan I, Lewin SR, Kent SJ, Juno JA, Bond KA, Williamson DA, Holmes NE, Smibert OC, Gordon CL, Trubiano JA, Kotsimbos TC, Cheng AC, ..., Xu J, Sonehara K, Ishii KJ, Namkoong H, Okada Y, Peiris M, Hui DS, Poon LL, Doherty PC, Nguyen TH, Valkenburg SA, Kedzierska K. HLA-B*15:01-positive severe COVID-19 patients lack CD8+ T cell pools with highly expanded public clonotypes. Proc Natl Acad Sci U S A 122, e2503145122 (2025)

  10. Shimada T, Tanabe N, Chubachi S, Asakura T, Namkoong H, Tanaka H, Azekawa S, Otake S, Nakagawara K, Fukushima T, Watase M, Maetani T, Shiraishi Y, Terai H, Sasaki M, Ueda S, Kato Y, Harada N, Suzuki S, Yoshida S, Tateno H, Yamada Y, Jinzaki M, Hirai T, Okada Y, Koike R, Ishii M, Kimura A, Imoto S, Miyano S, Ogawa S, Kanai T, Fukunaga K. Extent of pulmonary involvement on admission predicts long-term pulmonary and muscular sequelae of COVID-19: A longitudinal computed tomography study. Respir Investig 63, 1215–1220 (2025)

  11. Shirai Y, Enomoto T, Takeda Y, Edahiro R, Takahashi-Itoh M, Noda Y, Adachi Y, Nakayama M, Kawasaki T, Koba T, Futami Y, Yoshimura H, Amiya S, Hara R, Yamamoto M, Nakatsubo D, Suga Y, Naito M, Masuhiro K, Matsuki T, Hirata H, Iwahori K, Nagatomo I, Miyake K, Koyama S, Fukushima K, Shiroyama T, Naito Y, Futami S, Natsume-Kitatani Y, Ose N, Funaki S, Nojima S, Shichino S, Yanagawa M, Shintani Y, Nogami-Itoh M, Adachi J, Inoue Y, Tomonaga T, Okada Y, Mizuguchi K, Kumanogoh A. Serum vesicle biomarkers reflect the disease activity of idiopathic pulmonary fibrosis. J Transl Med 23, 1102 (2025)

  12. Masuo Y, Murakami A, Akamine R, Iri O, Uno S, Murata K, Nishitani K, Ito H, Watanabe R, Fujii T, Iwasaki T, Nakamura S, Kuriyama S, Morita Y, Murakawa Y, Terao C, Okada Y, Hashimoto M, Matsuda S, Ueno H, Yoshitomi H. Stem-like and effector peripheral helper T cells comprise distinct subsets in rheumatoid arthritis. Sci Immunol 10, eadt3955 (2025)

  13. Murakami A, Akamine R, Tanaka S, Murata K, Nishitani K, Ito H, Watanabe R, Fujii T, Iwasaki T, Masuo Y, Iri O, Nakamura S, Kuriyama S, Morita Y, Murakawa Y, Terao C, Okada Y, Hashimoto M, Matsuda S, Ueno H, Yoshitomi H. Human CD4+ T cells regulate peripheral immune responses in rheumatoid arthritis via insulin-like growth factor–like family member 2. Sci Immunol 10, eadr3838 (2025)

  14. Watase M, Shiraishi Y, Chubachi S, Tanabe N, Maetani T, Asakura T, Namkoong H, Tanaka H, Shimada T, Azekawa S, Otake S, Fukushima T, Nakagawara K, Masaki K, Terai H, Mochimaru T, Sasaki M, Ueda S, Kato Y, Harada N, Suzuki S, Yoshida S, Tateno H, Yamada Y, Jinzaki M, Okada Y, Koike R, Ishii M, Kimura A, Imoto S, Miyano S, Ogawa S, Kanai T, Fukunaga K. Coronary Artery Calcification on Chest Computed Tomography as a Predictor of Cardiovascular Adverse Events in Patients With COVID-19 ― A Multicenter Retrospective Study in Japan ―. Circ J 89, 373–381 (2025)

  15. Guccione C, Patel L, Tomofuji Y, McDonald D, Gonzalez A, Sepich-Poore GD, Sonehara K, Zakeri M, Chen Y, Dilmore AH, Damle N, Baranzini SE, Hightower G, Nakatsuji T, Gallo RL, Langmead B, Okada Y, Curtius K, Knight R. Incomplete human reference genomes can drive false sex biases and expose patient-identifying information in metagenomic data. Nat Commun 16, 825 (2025)

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