Method for efficiently detect structural variations with long read sequencing data

• Project/Area Number: 17K07264
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: System genome science
• Research Institution: Shizuoka Prefectural Hospital Organization (2021-2022); Institute of Physical and Chemical Research (2017-2020)
• Principal Investigator: Kosugi Shunichi 地方独立行政法人静岡県立病院機構静岡県立総合病院(救急診療部、循環器病診療部、がん診療部、臨床診療部, リサーチサポートセンター, 研究員 (30365457)
• Project Period (FY): 2017-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2019: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000); Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: ゲノムシークエンシング / ロングリード / 構造変異 / タンデムリピート / 全ゲノムシークエンシング / structural variation / sv / long read / structurally variation / PacBio / chromium

Outline of Final Research Achievements

We have developed software (LRsv) to efficiently and accurately detect genomic structural variation (SV) using long reads. We found that about half of the human SVs detected using long reads were insertions and deletions detected in the tandem repeat (TR) region, and many of these were copy number mutations involving an increase or decrease in the copy number of the TR repeat unit. LRsv differs from conventional long-read SV detection tools in that it distinguishes between copy number mutations detected in the TR region and SVs detected in other regions. Furthermore, LRsv also performs repeat and retroelement homology analysis of detected insertions and duplications, thus revealing SV characteristics not found in conventional tools.

Academic Significance and Societal Importance of the Research Achievements

ゲノム構造変異（SV）は、個人間のゲノムの違いのうち50塩基対以上の長さの変異のことで、さまざまなヒト疾患の要因になると考えられている。近年比較的安価に利用できるようになったロングリードシークエンシングを用いてSVを検出するためのソフトウェア（LRsv）を開発した。LRsvの特徴は、タンデムリピート領域に存在するリピートコピー数変異とそれ以外の領域のSVを区別して検出することにある。このため、本ツールは従来のツールでは不可能であったゲノム構造の網羅的な解析を可能にし、ヒト疾患を含めた生物形質の原因となるSVやタンデムリピート変異の同定に役立つことが期待される。

Research Products

• [Journal Article] Variant Spectrum of von Hippel-Lindau (VHL) disease and its genomic heterogeneity in Japan. (2023)
  • Author(s): 1.Kenji Tamura, Yuki Kanazashi, Chiaki Kawada, Yuya Sekine, Kazuhiro Maejima, Shingo Ashida, Takashi Karashima, Shohei Kojima, Nickolas F Parrish, Shunichi Kosugi, Chikashi Terao, Shota Sasagawa, Masashi Fujita, Todd A Johnson, Yukihide Momozawa, Keiji Inoue, Taro Shuin, Hidewaki Nakagawa
  • Journal Title: Human Molecular Genetics Volume: Published online 11 March Issue: 12 Pages: 2046-2054
  • DOI: 10.1093/hmg/ddad039
  • Peer Reviewed / Open Access
• [Journal Article] Detection of trait-associated structural variations using short read sequencing. (2023)
  • Author(s): 1.Shunichi Kosugi, Yoichiro Kamatani, Katsutoshi Harada, Kohei Tomizuka, Yukihide Momozawa, Takayuki Morisaki, The Biobank Japan Project, and Chikashi Terao
  • Journal Title: Cell Genomics Volume: in press
  • Peer Reviewed / Open Access
• [Journal Article] Whole genome sequencing of 45 Japanese patients with intellectual disability. (2021)
  • Author(s): Chihiro Abe-Hatano, Aritoshi Iida, Shunichi Kosugi, Yukihide Momozawa, Chikashi Terao, Keiko Ishikawa, Mariko Okubo, Yasuo Hachiya, Hiroya Nishida, Kazuyuki Nakamura, Rie Miyata, Chie Murakami, Kan Takahashi, Kyoko Hoshino, Haruko Sakamoto, Sayaka Ohta, Masaya Kubota, Eri Takeshita, Akihiko Ishiyama et al.
  • Journal Title: American Journal of Medical Genetics - Part A Volume: 185 Issue: 5 Pages: 1468-1480
  • DOI: 10.1002/ajmg.a.62138
  • Peer Reviewed
• [Journal Article] Genome features of common vetch (Vicia sativa) in natural habitats. (2021)
  • Author(s): Kenta Shirasawa, Shunichi Kosugi, Kazuhiro Sasaki, Andrea Ghelfi, Koei Okazaki, Atsushi Toyoda, Hideki Hirakawa, Sachiko Isobe
  • Journal Title: Plant Direct Volume: 5 Issue: 10
  • DOI: 10.1002/pld3.352
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Endogenization and excision of human herpesvirus 6 in human genomes. (2020)
  • Author(s): Xiaoxi Liu, Shunichi Kosugi, Rie Koide, Yoshiki Kawamura, Jumpei Ito, Hiroki Miura, Nana Matoba, Motomichi Matsuzaki , and other 14 authors
  • Journal Title: PLOS Genetics Volume: 16 Issue: 8 Pages: 1008915-1008915
  • DOI: 10.1371/journal.pgen.1008915
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Prevalence and spectrum of pathogenic germline variants in Japanese patients with early-onset colorectal, breast, and prostate cancer. (2020)
  • Author(s): Xiaoxi Liu, Sadaaki Takata, Kyota Ashikawa, Tomomi Aoi, Shunichi Kosugi, Chikashi Terao, Nicholas F. Parrish, Koichi Matsuda, Hidewaki Nakagawa, Yoichiro Kamatani, Michiaki Kubo, and Yukihide Momozawa
  • Journal Title: JCO Clinical Oncology Volume: 4 Issue: 4 Pages: 183-191
  • DOI: 10.1200/po.19.00224
  • Peer Reviewed / Open Access
• [Journal Article] tappAS: a comprehensive computational framework for the analysis of the functional impact of differential splicing. (2020)
  • Author(s): Lorena de la Fuente, Angeles Arzalluz-Luque, Manuel Tardaguila, Hector del Risco, Cristina Marti, Sonia Tarazona, Pedro Salguero, Raymond Scott, Alberto Lerma, Ana Alastrue-Agudo, Pablo Bonilla, Jeremy R.B. Newman, Shunichi Kosugi, Lauren M. McIntyre, Victoria Moreno-Manzano, and Ana Conesa
  • Journal Title: Genome Biology Volume: 21 Issue: 1 Pages: 119-119
  • DOI: 10.1186/s13059-020-02028-w
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Comprehensive evaluation of structural variation detection algorithms for whole genome sequencing. (2019)
  • Author(s): 3.Shunichi Kosugi, Yukihide Momozawa, Xiaoxi Liu, Chikashi Terao, Michiaki Kubo, and Yoichiro Kamatani
  • Journal Title: Genome Biology Volume: 20 Issue: 1 Pages: 117-117
  • DOI: 10.1186/s13059-019-1720-5
  • Peer Reviewed / Open Access
• [Journal Article] A novel PAK3 pathogenic variant identified in two siblings from a Japanese family with X-linked intellectual disability: case report and review of the literature. (2019)
  • Author(s): 4.Aritoshi Iida, Kyoko Takano, Eri Takeshita, Chihiro Abe Hatano, Shinichi Hirabayashi, Yuji Inaba, Shunichi Kosugi, Yoichiro Kamatani, Yukihide Momozawa, Michiaki Kubo, Eiji Nakagawa, Ken Inoue, and Yu-ichi Goto
  • Journal Title: Cold Spring Harb. Mol. Case Stud. Volume: 5 Issue: 6 Pages: a003988-a003988
  • DOI: 10.1101/mcs.a003988
  • Peer Reviewed / Open Access
• [Journal Article] A novel intragenic deletion in OPHN1 in a Japanese patient with Dandy-Walker malformation. (2019)
  • Author(s): Iida A, Takeshita E, Kosugi S, Kamatani Y, Momozawa Y, Kubo M, Nakagawa E, Kurosawa K, Inoue K, Goto YI
  • Journal Title: Human Genome Variation Volume: 6 Issue: 1 Pages: 1-4
  • DOI: 10.1038/s41439-018-0032-8
  • Peer Reviewed / Open Access
• [Presentation] Comprehensive evaluation of structural variation detection algorithms for whole genome sequencing (2019)
  • Author(s): Shunichi Kosugi
  • Organizer: 第８回生命医薬情報学連合大会
• [Presentation] Structural variations in whole genome sequencing data from 1300 disease genomes (2017)
  • Author(s): 小杉俊一、桃沢幸秀、久保允人、鎌谷洋一郎
  • Organizer: 第6回生命医薬情報連合大会
• [Remarks] MOPline: Detection of Structural Variants
  • URL: https://github.com/stat-lab/MOPline