Publications

Selected publication and preprints
Full publication list
Preprints

You can also find my articles and recent preprints on my Google Scholar profile.

Selected publication and preprints

Identifying the causal allele in the CD40 autoimmune locus enables discovery of context-specific trans-effects in B cells

Published in bioRxiv, 2026

Thousands of genetic variants are associated with autoimmune diseases, but causal variants, their mechanisms, and the pathogenic context in which they act are elusive. Knowledge of pathogenic contexts may enable effective targeted therapies, instead of broad immunosuppressive approaches. First, to focus on the genetics of immune response, we used surface marker CITE-seq data from 1,055,857 peripheral blood mononuclear cells from 356 individuals. We defined genetic associations to 148 surface proteins across eight cell types. We observed a signal in the CD40 locus, implicated in rheumatoid arthritis (RA) and other autoimmune conditions. RA risk variants increased CD40 protein expression by ~20% on B cells, but with minimal mRNA effects. Second, we deployed base-resolution genome editing, with CRAFT-seq, capturing genomic DNA sequence at the edited site and multimodal phenotypes at single-cell resolution. We defined a single causal allele, rs1883832, within the Kozak motif. Third, we edited this allele in primary B cells and conducted CRAFT-seq to demonstrate trans-effects in >200 genes. These effects were only in the light zone germinal center-like state. Importantly, these trans-effects were not seen in population-scale cohorts of unstimulated B cells. This represents a framework to define disease causal alleles, their cis- and trans-effects. It demonstrates the power of defining causal genetic variation to find trans-effects through editing, which cannot easily be found in population studies. Study overview

Recommended citation: Yoshihiko Tomofuji, Zepeng Mu, Hafsa Mire, Yu Zhao, Cassidy Liu, Vidya Jayanthi, Nicholas Sugiarto, Accelerating Medicines Partnership®: RA/SLE Network, Jeffrey A. Sparks, & Soumya Raychaudhuri†. Identifying the causal allele in the CD40 autoimmune locus enables discovery of context-specific trans-effects in B cells. bioRxiv 2026.07.29.741564 (2026) doi:10.64898/2026.07.29.741564. https://www.biorxiv.org/content/10.64898/2026.07.29.741564v1

Quantification of the escape from X chromosome inactivation with the million cell-scale human single-cell omics datasets reveals heterogeneity of escape across cell types and tissues

Published in bioRxiv, 2023

One of the two X chromosomes of females is silenced through X chromosome inactivation (XCI) to compensate for the difference in the dosage between sexes. Among the X-linked genes, several genes escape from XCI, which could contribute to the differential gene expression between the sexes. However, the differences in the escape across cell types and tissues are still poorly characterized because no methods could directly evaluate the escape under a physiological condition at the cell-cluster resolution with versatile technology. Here, we developed a method, single-cell Level inactivated X chromosome mapping (scLinaX), which directly quantifies relative gene expression from the inactivated X chromosome with droplet-based single-cell RNA-sequencing (scRNA-seq) data. Study overview

Recommended citation: Yoshihiko Tomofuji†, Ryuya Edahiro, Yuya Shirai, Kian Hong Kock, Kyuto Sonehara, Qingbo S. Wang, Shinichi Namba, Jonathan Moody, Yoshinari Ando, Akari Suzuki, Tomohiro Yata, Kotaro Ogawa, Ho Namkoong, Quy Xiao Xuan Lin, Eliora Violain Buyamin, Le Min Tan, Radhika Sonthalia, Kyung Yeon Han, Hiromu Tanaka, Ho Lee, Asian Immune Diversity Atlas Network, Japan COVID-19 Task Force, The BioBank Japan Project, Tatsusada Okuno, Boxiang Liu, Koichi Matsuda, Koichi Fukunaga, Hideki Mochizuki, Woong-Yang Park, Kazuhiko Yamamoto, Chung-Chau Hon, Jay W. Shin, Shyam Prabhakar, Atsushi Kumanogoh, & Yukinori Okada†. Quantification of the escape from X chromosome inactivation with the million cell-scale human single-cell omics datasets reveals heterogeneity of escape across cell types and tissues. bioRxiv 2023.10.14.561800 (2023) doi:10.1101/2023.10.14.561800. https://www.biorxiv.org/content/10.1101/2023.10.14.561800v1

Reconstruction of the personal information from human genome reads in gut metagenome sequencing data

Published in Nature Microbiology, 2023

It is known that a small amount of human DNA is contained in the stool samples. Using a statistical genetics approach, we asked how much personal information is contained in the human reads in the metagenome shotgun sequencing data. We demonstrated that human reads in the metagenome shotgun sequencing data were sufficient to identify an individual’s genetics sex, genetic ancestry, and matched genotype data. Study overview

Recommended citation: Tomofuji, Y.†, Sonehara, K., Kishikawa, T., Maeda, Y., Ogawa, K., Kawabata, S., Nii, T., Okuno, T., Oguro-Igashira, E., Kinoshita, M., Takagaki, M., Yamamoto, K., Kurakawa, T., Yagita-Sakamaki, M., Hosokawa, A., Motooka, D., Matsumoto, Y., Matsuoka, H., Yoshimura, M., Ohshima, S., Nakamura, S., Inohara, H., Kishima, H., Mochizuki, H., Takeda, K., Kumanogoh, A. & Okada, Y.† Reconstruction of the personal information from human genome reads in gut metagenome sequencing data. Nature Microbiology 8, 1079–1094 (2023). https://doi.org/10.1038/s41564-023-01381-3

Full publication list

The ‘*’ and ‘†’ symbols indicate equal contribution and correspondence, respectively, in the following list.

Tomofuji, Y.†, Sonehara, K., Kishikawa, T., Maeda, Y., Ogawa, K., Kawabata, S., Nii, T., Okuno, T., Oguro-Igashira, E., Kinoshita, M., Takagaki, M., Yamamoto, K., Kurakawa, T., Yagita-Sakamaki, M., Hosokawa, A., Motooka, D., Matsumoto, Y., Matsuoka, H., Yoshimura, M., Ohshima, S., Nakamura, S., Inohara, H., Kishima, H., Mochizuki, H., Takeda, K., Kumanogoh, A. & Okada, Y.† Reconstruction of the personal information from human genome reads in gut metagenome sequencing data. Nature Microbiology 8, 1079–1094 (2023).
Edahiro, R.*, Shirai, Y.*, Takeshima, Y., Sakakibara, S., Yamaguchi, Y., Murakami, T., Morita, T., Kato, Y., Liu, Y.-C., Motooka, D., Naito, Y., Takuwa, A., Sugihara, F., Tanaka, K., Wing, J. B., Sonehara, K., Tomofuji, Y., Japan COVID-19 Task Force, Namkoong, H., Tanaka, H., Lee, H., Fukunaga, K., Hirata, H., Takeda, Y., Okazaki, D., Kumanogoh, A.† & Okada, Y.† Single-cell analyses and host genetics highlight the role of innate immune cells in COVID-19 severity. Nature Genetics 55, 753–767 (2023).
Tomofuji, Y.*, Suzuki, K.*, Kishikawa, T., Shojima, N., Hosoe, J., Inagaki, K., Matsubayashi, S., Ishihara, H., Watada, H., Ishigaki, Y., Yamanashi, Y., Furukawa, Y., Morisaki, T., Kamatani, Y., Muto, K., Nagai, A., Obara, W., Yamaji, K., Takahashi, K., Asai, S., Takahashi, Y., Suzuki, T., Sinozaki, N., Yamaguchi, H., Minami, S., Murayama, S., Yoshimori, K., Nagayama, S., Obata, D., Higashiyama, M., Masumoto, A., Koretsune, Y., Inohara, H., Murakami, Y., Matsuda, K., Okada, Y.†, Yamauchi, T.†, Kadowaki, T.†, & The BioBank Japan Project. Identification of serum metabolome signatures associated with retinal and renal complications of type 2 diabetes. Communications Medicine 3, 5 (2023).
Tomofuji, Y.†, Kishikawa, T., Maeda, Y., Ogawa, K., Otake-Kasamoto, Y., Kawabata, S., Nii, T., Okuno, T., Oguro-Igashira, E., Kinoshita, M., Takagaki, M., Oyama, N., Todo, K., Yamamoto, K., Sonehara, K., Yagita, M., Hosokawa, A., Motooka, D., Matsumoto, Y., Matsuoka, H., Yoshimura, M., Ohshima, S., Shinzaki, S., Nakamura, S., Iijima, H., Inohara, H., Kishima, H., Takehara, T., Mochizuki, H., Takeda, K., Kumanogoh, A. & Okada, Y.† Prokaryotic and viral genomes recovered from 787 Japanese gut metagenomes revealed microbial features linked to diets, populations, and diseases. Cell Genomics 2, 100219 (2022).
Itotagawa, E., Tomofuji, Y., Kato, Y., Konaka, H., Tsujimoto, K., Park, J., Nagira, D., Hirayama, T., Jo, T., Hirano, T., Morita, T., Nishide, M., Nishida, S., Shima, Y., Narazaki, M., Okada, Y., Takamatsu, H. & Kumanogoh, A. SLE stratification based on BAFF and IFN-I bioactivity for biologics and implications of BAFF produced by glomeruli in lupus nephritis. Rheumatology 62, 1988–1997 (2023).
Yan, M., Komatsu, N., Muro, R., Huynh, N. C.-N., Tomofuji, Y., Okada, Y., Suzuki, H. I., Takaba, H., Kitazawa, R., Kitazawa, S., Pluemsakunthai, W., Mitsui, Y., Satoh, T., Okamura, T., Nitta, T., Im, S.-H., Kim, C. J., Kollias, G., Tanaka, S., Okamoto, K., Tsukasaki, M. & Takayanagi, H. ETS1 governs pathological tissue-remodeling programs in disease-associated fibroblasts. Nature Immunology 23, 1330–1341 (2022).
Kishikawa, T., Tomofuji, Y., Inohara, H. & Okada, Y. OMARU: a robust and multifaceted pipeline for metagenome-wide association study. NAR Genomics and Bioinformatics 4, lqac019 (2022).
Tomofuji, 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. Annals of the Rheumatic Diseases 81, 278–288 (2022).
Tomofuji, Y.*, Maeda, Y.*, Oguro-Igashira, E.*, Kishikawa, T., Yamamoto, K., Sonehara, K., Motooka, D., Matsumoto, Y., Matsuoka, H., Yoshimura, M., Yagita, M., Nii, T., Ohshima, S., Nakamura, S., Inohara, H., Takeda, K., Kumanogoh, A. & Okada, Y. Metagenome-wide association study revealed disease-specific landscape of the gut microbiome of systemic lupus erythematosus in Japanese. Annals of the Rheumatic Diseases 80, 1575–1583 (2021).
Harano, Y., Ishikawa, Y., Hattori, K., Ichinose, M., Tomofuji, Y., Okano, H., Owada, G., Kimura, Y., Nanao, T., Fujimoto, J., Nishizawa, H., Iiola, Y., Osada, J., Fujiwara, M. & Kita, Y. A case of complete atrioventricular block in secondary hemophagocytic syndrome/hemophagocytic lymphohistiocytosis recovered by plasma exchange and cytokine absorbing therapy with AN69ST continuous hemodiafiltration. Immunological Medicine 43, 171–178 (2020).
Nitta, T., Tsutsumi, M., Nitta, S., Muro, R., Suzuki, E. C., Nakano, K., Tomofuji, Y., Sawa, S., Okamura, T., Penninger, J. M. & Takayanagi, H. Fibroblasts as a source of self-antigens for central immune tolerance. Nature Immunology 21, 1172–1180 (2020).
Tomofuji, Y.*, Takaba, H.*, Suzuki, H. I., Benlaribi, R., Martinez, C. D. P., Abe, Y., Morishita, Y., Okamura, T., Taguchi, A., Kodama, T. & Takayanagi, H. Chd4 choreographs self-antigen expression for central immune tolerance. Nature Immunology 21, 892–901 (2020).
Tomofuji, Y., Ishikawa, Y., Hattori, K., Fujiwara, M. & Kita, Y. Successful treatment of refractory acute lupus haemophagocytic syndrome using rituximab: a case report. Modern Rheumatology Case Reports 4, 222–228 (2020).
Nitta, T., Kochi, Y., Muro, R., Tomofuji, Y., Okamura, T., Murata, S., Suzuki, H., Sumida, T., Yamamoto, K. & Takayanagi, H. Human thymoproteasome variations influence CD8 T cell selection. Science Immunology 2, eaan5165 (2017).
Takaba, H., Morishita, Y., Tomofuji, Y., Danks, L., Nitta, T., Komatsu, N., Kodama, T. & Takayanagi, H. Fezf2 orchestrates a thymic program of self-antigen expression for immune tolerance. Cell 163, 975–987 (2015).

Preprints