Annual Report 2023

Division of Translational Informatics

Katsuya Tsuchihara, Riu Yamashita, Sachiyo Mimaki, Izumi Miki, Sunggi Chi, Shunsuke Sakai, Ryosuke Nomura, Megumi Iwakura, Yutaka Suzuki, Ayako Suzuki, Junko Zenkoh

Introduction

 In cancer cells, transcription and translation are regulated differently than in normal cells, leading to the expression of cancer-specific characteristics. However, there are few reports detailing the specific transcriptional and translational regulation in each cancer cell and how they interact with their surrounding environment. Large-scale data is being accumulated, including omics information such as genome, transcriptome, metabolome, microbiome, and proteome, along with CT, MRI, and pathology images. It is crucial to develop databases that consolidate these data and technologies that enable cross-sectional analysis.

The Team and What We Do

 We are developing technologies for analyzing large amounts of data with high information content, including single or multi-omics layers, and extracting biological and medical information. For example, we are integrating and analyzing genomic, transcriptomic, and metagenomic sequence data with medical information. In particular, single-cell and spatial omics analyses are still in their early stages and lack established analysis methods, so our main focus is on developing new technologies in this area. Additionally, we are working on extracting regions of interest (ROIs) from pathology, CT, and X-ray images using precise machine learning models to construct cancer prognosis prediction models that integrate multi-omics data.

Research Activities

 We published two papers based on single-cell omics analysis data for lung and colorectal cancer. Additionally, we developed a technology for de novo analysis of spatial omics data, as well as a method for effectively measuring the expression of characteristic cell clusters inside and outside the field of view. The latter has been released as SKNY. In collaboration with the Tohoku Medical Megabank Organization, we also published CHIPs-DB, a database of clonal hematopoiesis of indeterminate potential (CHIP) specific to the Japanese population. Furthermore, we reported the selection of 37 SNVs that can most effectively distinguish Japanese individuals, along with their application in mass array technology. We also improved and released the bacterial flora analysis tool QINDAO (Quantitative INDex of Alpha diversity Overview) to support shotgun metagenomic data.

Education

 Unit Director Yamashita delivered several lectures as a visiting faculty member at the Graduate School of Frontier Sciences, University of Tokyo, and the Graduate School of Life Sciences, Tokyo University of Science. We welcomed one physician-scientist and one trainee from the Department of Gastroenterological and General Surgery at Kyushu University, providing them with training in data and AI analysis. Additionally, three staff members participated in a hands-on machine learning and AI training seminar (comprising six sessions) hosted by the Hospital East. Over the year, our laboratory also hosted 25 online bioinformatics seminars. Also, two students participated in the Young Life Information Researchers' Association and actively exchanged information.

Future Prospects

 The MONSTAR-SCREEN-3, which started in 2024 and focuses on solid and hematological cancers, is expected to generate multi-omics data, including genome, proteome, metabolome, transcriptome, spatial transcriptome, and microbiome information. By conducting integrated analyses of these large-scale data, we aim to contribute to cancer research.

List of papers published in 2023

Journal

1. Shiraishi K, Takahashi A, Momozawa Y, Daigo Y, Kaneko S, Kawaguchi T, Kunitoh H, Matsumoto S, Horinouchi H, Goto A, Honda T, Shimizu K, Torasawa M, Takayanagi D, Saito M, Saito A, Ohe Y, Watanabe SI, Goto K, Tsuboi M, Tsuchihara K, Takata S, Aoi T, Takano A, Kobayashi M, Miyagi Y, Tanaka K, Suzuki H, Maeda D, Yamaura T, Matsuda M, Shimada Y, Mizuno T, Sakamoto H, Yoshida T, Goto Y, Yoshida T, Yamaji T, Sonobe M, Toyooka S, Yoneda K, Masago K, Tanaka F, Hara M, Fuse N, Nishizuka SS, Motoi N, Sawada N, Nishida Y, Kumada K, Takeuchi K, Tanno K, Yatabe Y, Sunami K, Hishida T, Miyazaki Y, Ito H, Amemiya M, Totsuka H, Nakayama H, Yokose T, Ishigaki K, Nagashima T, Ohtaki Y, Imai K, Takasawa K, Minamiya Y, Kobayashi K, Okubo K, Wakai K, Shimizu A, Yamamoto M, Iwasaki M, Matsuda K, Inazawa J, Shiraishi Y, Nishikawa H, Murakami Y, Kubo M, Matsuda F, Kamatani Y, Hamamoto R, Matsuo K, Kohno T. Identification of telomere maintenance gene variations related to lung adenocarcinoma risk by genome-wide association and whole genome sequencing analyses. Cancer communications (London, England), 44:287-293, 2024

2. Sunami K, Naito Y, Saigusa Y, Amano T, Ennishi D, Imai M, Kage H, Kanai M, Kenmotsu H, Komine K, Koyama T, Maeda T, Morita S, Sakai D, Hirata M, Ito M, Kozuki T, Sakashita H, Horinouchi H, Okuma Y, Takashima A, Kubo T, Hironaka S, Segawa Y, Yakushijin Y, Bando H, Makiyama A, Suzuki T, Kinoshita I, Kohsaka S, Ohe Y, Ishioka C, Yamamoto K, Tsuchihara K, Yoshino T. A Learning Program for Treatment Recommendations by Molecular Tumor Boards and Artificial Intelligence. JAMA oncology, 10:95-102, 2024

3. Kage H, Akiyama N, Chang H, Shinozaki-Ushiku A, Ka M, Kawata J, Muto M, Okuma Y, Okita N, Tsuchihara K, Kikuchi J, Shirota H, Hayashi H, Kokuryo T, Yachida S, Hirasawa A, Kubo M, Kenmotsu H, Tanabe M, Ushiku T, Muto K, Seto Y, Oda K. Patient survey on cancer genomic medicine in Japan under the national health insurance system. Cancer science, 115:954-962, 2024

4. Tabata S, Umemura S, Narita M, Udagawa H, Ishikawa T, Tsuboi M, Goto K, Ishii G, Tsuchihara K, Ochiai A, Kobayashi SS, Soga T, Makinoshima H. Metabolic Hallmarks for Purine Nucleotide Biosynthesis in Small Cell Lung Carcinoma. Molecular cancer research, 22:82-93, 2024

5. Shitara K, Muro K, Watanabe J, Yamazaki K, Ohori H, Shiozawa M, Takashima A, Yokota M, Makiyama A, Akazawa N, Ojima H, Yuasa Y, Miwa K, Yasui H, Oki E, Sato T, Naitoh T, Komatsu Y, Kato T, Mori I, Yamanaka K, Hihara M, Soeda J, Misumi T, Yamamoto K, Yamashita R, Akagi K, Ochiai A, Uetake H, Tsuchihara K, Yoshino T. Baseline ctDNA gene alterations as a biomarker of survival after panitumumab and chemotherapy in metastatic colorectal cancer. Nature medicine, 30:730-739, 2024

6. Nakamura Y, Yamashita R, Okamoto W, Komatsu Y, Yuki S, Ueno M, Kato K, Taniguchi H, Kagawa Y, Denda T, Hara H, Esaki T, Moriwaki T, Sunakawa Y, Oki E, Nagashima F, Nishina T, Satoh T, Kawakami H, Yamaguchi K, Ohtsubo K, Kato T, Horita Y, Tsuji A, Yasui H, Goto M, Hamamoto Y, Wakabayashi M, Ikeno T, Shitara K, Bando H, Tsuchihara K, Miki I, Ichiki H, Ohtsu A, Yoshino T. Efficacy of Targeted Trials and Signaling Pathway Landscape in Advanced Gastrointestinal Cancers From SCRUM-Japan GI-SCREEN: A Nationwide Genomic Profiling Program. JCO precision oncology, 7:e2200653, 2023

7. Kage H, Oda K, Muto M, Tsuchihara K, Okita N, Okuma Y, Kikuchi J, Shirota H, Hayashi H, Kokuryo T, Sakai D, Hirasawa A, Kubo M, Kenmotsu H, Akiyama N, Shinozaki-Ushiku A, Tanabe M, Ushiku T, Miyagawa K, Seto Y. Human resources for administrative work to carry out a comprehensive genomic profiling test in Japan. Cancer science, 114:3041-3049, 2023

8. Watanabe J, Muro K, Shitara K, Yamazaki K, Shiozawa M, Ohori H, Takashima A, Yokota M, Makiyama A, Akazawa N, Ojima H, Yuasa Y, Miwa K, Yasui H, Oki E, Sato T, Naitoh T, Komatsu Y, Kato T, Hihara M, Soeda J, Misumi T, Yamamoto K, Akagi K, Ochiai A, Uetake H, Tsuchihara K, Yoshino T. Panitumumab vs Bevacizumab Added to Standard First-line Chemotherapy and Overall Survival Among Patients With RAS Wild-type, Left-Sided Metastatic Colorectal Cancer: A Randomized Clinical Trial. JAMA, 329:1271-1282, 2023

9. Naito Y, Mishima S, Akagi K, Hayashi N, Hirasawa A, Hishiki T, Igarashi A, Ikeda M, Kadowaki S, Kajiyama H, Kato M, Kenmotsu H, Kodera Y, Komine K, Koyama T, Maeda O, Miyachi M, Nishihara H, Nishiyama H, Ohga S, Okamoto W, Oki E, Ono S, Sanada M, Sekine I, Takano T, Tao K, Terashima K, Tsuchihara K, Yatabe Y, Yoshino T, Baba E. Japanese Society of Medical Oncology/Japan Society of Clinical Oncology/Japanese Society of Pediatric Hematology/Oncology-led clinical recommendations on the diagnosis and use of tropomyosin receptor kinase inhibitors in adult and pediatric patients with neurotrophic receptor tyrosine kinase fusion-positive advanced solid tumors. International journal of clinical oncology, 28:827-840, 2023

10. Mishima S, Naito Y, Akagi K, Hayashi N, Hirasawa A, Hishiki T, Igarashi A, Ikeda M, Kadowaki S, Kajiyama H, Kato M, Kenmotsu H, Kodera Y, Komine K, Koyama T, Maeda O, Miyachi M, Nishihara H, Nishiyama H, Ohga S, Okamoto W, Oki E, Ono S, Sanada M, Sekine I, Takano T, Tao K, Terashima K, Tsuchihara K, Yatabe Y, Yoshino T, Baba E. Japanese Society of Medical Oncology/Japan Society of Clinical Oncology/Japanese Society of Pediatric Hematology/Oncology-led clinical recommendations on the diagnosis and use of immunotherapy in patients with high tumor mutational burden tumors. International journal of clinical oncology, 28:941-955, 2023

11. Mishima S, Naito Y, Akagi K, Hayashi N, Hirasawa A, Hishiki T, Igarashi A, Ikeda M, Kadowaki S, Kajiyama H, Kato M, Kenmotsu H, Kodera Y, Komine K, Koyama T, Maeda O, Miyachi M, Nishihara H, Nishiyama H, Ohga S, Okamoto W, Oki E, Ono S, Sanada M, Sekine I, Takano T, Tao K, Terashima K, Tsuchihara K, Yatabe Y, Yoshino T, Baba E. Japanese Society of Medical Oncology/Japan Society of Clinical Oncology/Japanese Society of Pediatric Hematology/Oncology-led clinical recommendations on the diagnosis and use of immunotherapy in patients with DNA mismatch repair deficient (dMMR) tumors, third edition. International journal of clinical oncology, 28:1237-1258, 2023

12. Tanaka T, Umemura S, Miyoshi T, Nakai T, Noritake O, Suzuki J, Tane K, Samejima J, Aokage K, Mimaki S, Tsuchihara K, Taki T, Miyazaki S, Watanabe R, Sakashita S, Sakamoto N, Kojima M, Goto K, Ikeda N, Tsuboi M, Ishii G. The prognostic impact of a high number of peritumoral alveolar macrophages in neuroendocrine carcinoma in the lung. Pathology international, 73:497-508, 2023

13. Nakai C, Mimaki S, Matsushima K, Shinozaki E, Yamazaki K, Muro K, Yamaguchi K, Nishina T, Yuki S, Shitara K, Bando H, Suzuki Y, Akagi K, Nomura S, Fujii S, Sugiyama M, Nishida N, Mizokami M, Koh Y, Koshizaka T, Okada H, Abe Y, Ohtsu A, Yoshino T, Tsuchihara K. Regulation of MEK inhibitor selumetinib sensitivity by AKT phosphorylation in the novel BRAF L525R mutant. International journal of clinical oncology, 28:654-663, 2023

14. Du J, Kageyama SI, Yamashita R, Tanaka K, Okumura M, Motegi A, Hojo H, Nakamura M, Hirata H, Sunakawa H, Kotani D, Yano T, Kojima T, Hamaya Y, Kojima M, Nakamura Y, Suzuki A, Suzuki Y, Tsuchihara K, Akimoto T. Transposable elements potentiate radiotherapy-induced cellular immune reactions via RIG-I-mediated virus-sensing pathways. Communications biology, 6:818, 2023

15. Kajiwara T, Nishina T, Yamashita R, Nakamura Y, Shiozawa M, Yuki S, Taniguchi H, Hara H, Ohta T, Esaki T, Shinozaki E, Takashima A, Yamamoto Y, Yamazaki K, Yoshino T, Hyodo I. Sidedness-Dependent Prognostic Impact of Gene Alterations in Metastatic Colorectal Cancer in the Nationwide Cancer Genome Screening Project in Japan (SCRUM-Japan GI-SCREEN). Cancers, 15:5172, 2023

16. Oyoshi H, Du J, Sakai SA, Yamashita R, Okumura M, Motegi A, Hojo H, Nakamura M, Hirata H, Sunakawa H, Kotani D, Yano T, Kojima T, Nakamura Y, Kojima M, Suzuki A, Zenkoh J, Tsuchihara K, Akimoto T, Shibata A, Suzuki Y, Kageyama SI. Comprehensive single-cell analysis demonstrates radiotherapy-induced infiltration of macrophages expressing immunosuppressive genes into tumor in esophageal squamous cell carcinoma. Science advances, 9:eadh9069, 2023

17. Nakamura M, Kageyama SI, Hirata H, Tochinai T, Hojo H, Motegi A, Kanai A, Suzuki Y, Tsuchihara K, Akimoto T. Detection of Pretreatment Circulating Tumor DNA Predicts Recurrence after High-Dose Proton Beam Therapy for Early-Stage Non-Small Cell Lung Cancer. International journal of radiation oncology, biology, physics, 116:1085-1090, 2023

18. Hamaya Y, Suzuki A, Suzuki Y, Tsuchihara K, Yamashita R. Classification and characterization of alternative promoters in 26 lung adenocarcinoma cell lines. Japanese journal of clinical oncology, 53:97-104, 2023

19. Tanaka Y, Yamashita R, Kawashima J, Mori H, Kurokawa K, Fukuda S, Gotoh Y, Nakamura K, Hayashi T, Kasahara Y, Sato Y, Fukudo S. Further notice of omics profiles of fecal and oral microbiota change in irritable bowel syndrome patients with diarrhea and symptom exacerbation. Journal of gastroenterology, 58:427-428, 2023

20. Kudo H, Ishida N, Nobukuni T, Aoki Y, Saito S, Nishijima I, Terakawa T, Yamamoto M, Minegishi N, Yamashita R, Kumada K. Detection and Correction of Sample Misidentifications in a Biobank Using the MassARRAY System and Genomic Information. Biopreservation and biobanking, 2023