Development of multifactorial genome information processing technology for elucidating genetic the background of complex traits

• Project/Area Number: 19K06629
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 43060:System genome science-related
• Research Institution: The University of Tokyo (2020-2022); Osaka University (2019)
• Principal Investigator: Nakaya Akihiro 東京大学, 大学院新領域創成科学研究科, 特任教授 (60301149)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: ゲノム配列 / 配列変異 / 連鎖不平衡 / 解析パイプライン / ミトコンドリア / 電子顕微鏡 / 全ゲノムシーケンシング / 情報解析パイプライン / 画像処理 / ゲノム情報 / 数理モデル

Outline of Research at the Start

複雑な形質の遺伝的背景の解明に向けた多因子的なゲノム情報処理技術を開発する。ゲノムDNA配列変異間の連鎖不平衡を抽出して構造化する手法、および、空間的な形状や分布に関する形質を抽出して定量化する手法を開発する。構造化されたゲノム情報と定量化された形質情報の間の多因子的な関係を定式化する数理モデルを構築する手法を開発する。ミトコンドリア電子顕微鏡画像等に適用して疾患との関連性の評価を行う。実データに適用した結果を蓄積したデータベースを構築し、画像データもクエリーとして指定できるビジュアルな検索手法を開発する。検索結果を公共データと連係させてデータの解釈や注釈を支援する情報処理技術を開発する。

Outline of Final Research Achievements

We developed a method for extracting linkage disequilibrium blocks from mutation data for structuring genomic information. The method was implemented as software for extraction and visualization of intricate linkage disequilibrium blocks while scanning genomic DNA sequences of a sample set. We also developed a short-read whole genome sequencing (WGS) analysis pipeline. Software was developed to quantify traits related to spatial shape and distribution of tissues such as mitochondria and myofibrils from electron microscopy image data. We developed a pseudo-colorization method based on the classification information of tissues in images, and also developed a database of rectangular regions (ROIs) in images to which the classification information was added.

Academic Significance and Societal Importance of the Research Achievements

ゲノム配列データからの複雑な連鎖不平衡ブロックの抽出や電子顕微鏡画像データからの形質の定量を行うソフトウェアは十分には整備されていないため、独自に開発することによって解析対象の実データに合わせた開発や解析を手法自体の検討から行うことが可能となる。また、ソフトウェアとして実装することによってデータ解析に向けた手順や知見を汎用に共有することも可能となる。

Research Products

• [Journal Article] Identification of mild cognitive impairment subtypes predicting conversion to Alzheimer’s disease using multimodal data (2022)
  • Author(s): Kikuchi M, Kobayashi K, Itoh S, Kasuga K, Miyashita A, Ikeuchi T, Yumoto E, Kosaka Y, Fushimi Y, Takeda T, Manabe S, Hattori S; Alzheimer's Disease Neuroimaging Initiative; Nakaya A, Kamijo K, Matsumura Y
  • Journal Title: Computational and Structural Biotechnology Journal Volume: 20 Pages: 5296-5308
  • DOI: 10.1016/j.csbj.2022.08.007
  • Peer Reviewed / Open Access
• [Journal Article] A heterozygous LAMA5 variant may contribute to slowly progressive, vinculin-enhanced familial FSGS and pulmonary defects. (2022)
  • Author(s): Kaimori JY, Kikkawa Y, Motooka D, Namba-Hamano T, Takuwa A, Okazaki A, Kobayashi K, Tanigawa A, Kotani Y, Uno Y, Yoshimi K, Hattori K, Asahina Y, Kajimoto S, Doi Y, Oka T, Sakaguchi Y, Mashimo T, Sekiguchi K, Nakaya A, Nomizu M, Isaka Y.
  • Journal Title: JCI insight Volume: 7 Issue: 23 Pages: 522-524
  • DOI: 10.1172/jci.insight.158378
  • Peer Reviewed / Open Access
• [Journal Article] Long-term prognosis and genetic background of cardiomyopathy in 223 pediatric mitochondrial disease patients. (2021)
  • Author(s): Imai-Okazaki A, Matsunaga A, Yatsuka Y, Nitta KR, Kishita Y, Sugiura A, Sugiyama Y, Fushimi T, Shimura M, Ichimoto K, Tajika M, Tominaga M, Ebihara T, Matsuhashi T, Tsuruoka T, Kohda M, Hirata T, Harashima H, Nojiri S, Takeda A, Nakaya A, Kogaki S, Sakata Y, Ohtake A, Murayama K, Okazaki Y.
  • Journal Title: International Journal of Cardiology Volume: 341 Pages: 48-55
  • DOI: 10.1016/j.ijcard.2021.06.042
  • Peer Reviewed / Open Access
• [Journal Article] Genome-wide copy number variation analysis of hepatitis B infection in a Japanese population (2021)
  • Author(s): Kikuchi M, Kobayashi K, Nishida N, Sawai H, Sugiyama M, Mizokami M, Tokunaga K, Nakaya A
  • Journal Title: Human Genome Variation Volume: 8 Issue: 1 Pages: 22-22
  • DOI: 10.1038/s41439-021-00154-w
  • Peer Reviewed / Open Access
• [Journal Article] Cyclosporine A Treatment of Proteinuria in a New Case of MAFB-Associated Glomerulopathy without Extrarenal Involvement: A Case Report (2021)
  • Author(s): Kaimori J-Y, Mori T, Namba-Hamano T, Morimoto T, Takuwa A, Motooka D, Okazaki A, Kobayashi K, Asahina Y, Kajimoto S, Doi Y, Oka T, Sakaguchi Y, Nakaya A, Isaka Y
  • Journal Title: Nephron Volume: 145 Issue: 4 Pages: 445-450
  • DOI: 10.1159/000516248
  • Peer Reviewed / Open Access
• [Journal Article] Cooperation of LIM domain-binding 2 (LDB2) with EGR in the pathogenesis of schizophrenia. (2021)
  • Author(s): Ohnishi T, Kiyama Y, Arima-Yoshida F, Kadota M, Ichikawa T, Yamada K, Watanabe A, Ohba H, Tanaka K, Nakaya A, Horiuchi Y, Iwayama Y, Toyoshima M, Ogawa I, Shimamoto-Mitsuyama C, Maekawa M, Balan S, Arai M, Miyashita M, Toriumi K, et al.
  • Journal Title: EMBO Mol Med Volume: 13 Issue: 4
  • DOI: 10.15252/emmm.202012574
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Upregulated expression of a subset of genes in APP;ob/ob mice: Evidence of an interaction between diabetes‐linked obesity and Alzheimer’s disease (2021)
  • Author(s): Shinohara Mitsuru、Kikuchi Masataka、Onishi‐Takeya Miyuki、Tashiro Yoshitaka、Suzuki Kaoru、Noda Yasuhiro、Takeda Shuko、Mukouzono Masahiro、Nagano Seiichi、Fukumori Akio、Morishita Ryuichi、Nakaya Akihiro、Sato Naoyuki
  • Journal Title: FASEB BioAdvances Volume: - Issue: 5 Pages: 323-333
  • DOI: 10.1096/fba.2020-00151
  • Peer Reviewed / Open Access
• [Journal Article] Lipid pathology of the corpus callosum in schizophrenia and the potential role of abnormal gene regulatory networks with reduced microglial marker expression (2020)
  • Author(s): Shimamoto-Mitsuyama Chie、Nakaya Akihiro、Esaki Kayoko、Balan Shabeesh、Iwayama Yoshimi、Ohnishi Tetsuo、Maekawa Motoko、Toyota Tomoko、Dean Brian、Yoshikawa Takeo
  • Journal Title: Cerebral Cortex Volume: 31 Issue: 1 Pages: 448-462
  • DOI: 10.1093/cercor/bhaa236
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] スギ花粉症舌下免疫療法の効果の評価に向けた網羅的計測データの多因子的解析 (2020)
  • Author(s): 中谷明弘
  • Organizer: 第4回日本アレルギー学会関東地方会
  • Invited
• [Book] 東大式 生命データサイエンス即戦力講座 (2021)
  • Author(s): DSTEP教材作成委員会
  • Total Pages: 344
  • Publisher: 羊土社
  • ISBN: 9784758121170
• [Patent(Industrial Property Rights)] 集積集合データの製造装置、製造方法、プログラム、および記録媒体 (2019)
  • Inventor(s): 中谷明弘, 小林香織, 竹之内隆夫, 上條憲一
  • Industrial Property Rights Holder: 中谷明弘, 小林香織, 竹之内隆夫, 上條憲一
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2019-113456
  • Filing Date: 2019