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Development of a method for estimating integrated intra- and inter-cellular networks using single-cell spatial transcriptomics

Research Project

Project/Area Number 20K19915
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 62010:Life, health and medical informatics-related
Research InstitutionUniversity of Tsukuba

Principal Investigator

Tsuchiya Takaho  筑波大学, 医学医療系, 助教 (70853167)

Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2022: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywords細胞間相互作用 / 空間トランスクリプトーム / Highly variable genes / PLS回帰モデル / シングルセル / 回帰モデル / バイオインフォマティクス / システムバイオロジー / 1細胞空間トランスクプリプトーム / 数理モデリング / 解析ツール開発 / 1細胞空間トランスクリプトーム
Outline of Research at the Start

細胞間相互作用を介した遺伝子制御ネットワークは多細胞の多彩な機能を生み出し維持するため、これら機能の理解に重要である。しかしながら、細胞間相互作用と遺伝子制御ネットワークの同時推定は重要であるにも関わらず、計測技術の限界で未達成だった。そこで、近年報告された1細胞空間トランスクリプトームデータから細胞間相互作用と遺伝子制御ネットワークを同時推定して統合する手法を提案し、多細胞機能を読み解く。

Outline of Final Research Achievements

In this study, we developed an information analysis method called CCPLS (Cell-Cell Communication analysis by Partial Least Squares modeling) to estimate the impact of neighboring cell types on the highly variable genes (HVG) of a particular cell type, using single-cell spatial transcriptome data that simultaneously measures cellular gene expression and spatial coordinates. Evaluation experiments using simulation data demonstrated that CCPLS can accurately estimate cell-cell communications. Furthermore, applications to real data from the brain and colon allowed us to extract biologically interpretable cell-cell communications, demonstrating the effectiveness of this method.

Academic Significance and Societal Importance of the Research Achievements

CCPLSは1細胞空間トランスクリプトーム全般に適用可能で、細胞型の空間配置によって発現変動する遺伝子を抽出できることから、例えば、周囲に免疫細胞が少なく悪性度が高いとされる飛炎症性腫瘍など、細胞の微小環境に着目した創薬標的探索への応用が期待される。
また近年、いくつかの国際コンソーシアムを中心に、1細胞空間トランスクリプトームデータの収集と蓄積が進んでおり、CCPLSをこれらのデータに対して適用することで、基礎生物学から疾患研究まで、さまざまな生物学的知見の発見につながると期待される。

Report

(5 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (18 results)

All 2024 2023 2022 2021 2020 Other

All Journal Article (10 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 9 results,  Open Access: 8 results) Presentation (7 results) Remarks (1 results)

  • [Journal Article] The RNA-binding protein Msi2 regulates autophagy during myogenic differentiation2024

    • Author(s)
      Wang R, Kato F, Watson RY, Beedle AM, Call JA, Tsunoda Y, Noda T, Tsuchiya T, Kashima M, Hattori A, Ito T.
    • Journal Title

      Life Sci Alliance .

      Volume: 7 Issue: 5 Pages: e202302016-e202302016

    • DOI

      10.26508/lsa.202302016

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Transcription factor-binding k-mer analysis clarifies the cell type dependency of binding specificities and cis-regulatory SNPs in humans2023

    • Author(s)
      Tahara Saeko、Tsuchiya Takaho、Matsumoto Hirotaka、Ozaki Haruka
    • Journal Title

      BMC Genomics

      Volume: 24 Issue: 1

    • DOI

      10.1186/s12864-023-09692-9

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] DNA hypomethylation characterizes genes encoding tissue-dominant functional proteins in liver and skeletal muscle2023

    • Author(s)
      Maehara H.、Kokaji T.、Hatano A.、Suzuki Y.、Matsumoto M.、Nakayama K. I.、Egami R.、Tsuchiya T.、Ozaki H.、Morita K.、Shirai M.、Li D.、Terakawa A.、Uematsu S.、Hironaka K.、Ohno S.、Kubota H.、Araki H.、Miura F.、Ito T.、Kuroda S.
    • Journal Title

      Scientific Reports

      Volume: 13 Issue: 1 Pages: 19118-19118

    • DOI

      10.1038/s41598-023-46393-5

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] CCPLS reveals cell-type-specific spatial dependence of transcriptomes in single cells2022

    • Author(s)
      Tsuchiya Takaho、Hori Hiroki、Ozaki Haruka
    • Journal Title

      Bioinformatics

      Volume: 38 Issue: 21 Pages: 4868-4877

    • DOI

      10.1093/bioinformatics/btac599

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] In vivo transomic analyses of glucose-responsive metabolism in skeletal muscle reveal core differences between the healthy and obese states.2022

    • Author(s)
      Kokaji T, Eto M, Hatano A, Yugi K, Morita K, Ohno S, Fujii M, Hironaka KI, Ito Y, Egami R, Uematsu S, Terakawa A, Pan Y, Maehara H, Li D, Bai Y, Tsuchiya T, Ozaki H, Inoue H, Kubota H, Suzuki Y, Hirayama A, Soga T, Kuroda S.
    • Journal Title

      Sci Rep

      Volume: 12 Issue: 1 Pages: 13719-13719

    • DOI

      10.1038/s41598-022-17964-9

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identifying potential regulators of JAGGED1 expression in portal mesenchymal cells2022

    • Author(s)
      Nishino Teppei、Yoshihara Masaharu、Nakayama Takahiro、Tsuchiya Takaho、Tahara Saeko、Ozaki Haruka、Takahashi Satoru
    • Journal Title

      BMC Research Notes

      Volume: 15 Issue: 1

    • DOI

      10.1186/s13104-022-06058-4

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] ゲノム編集技術と大規模ゲノムデータに基づく遺伝子治療2021

    • Author(s)
      土屋貴穂
    • Journal Title

      BIO Clinica

      Volume: Vol.36(5) Pages: 448-452

    • Related Report
      2021 Research-status Report
  • [Journal Article] Trans-omic analysis reveals obesity-associated dysregulation of inter-organ metabolic cycles between the liver and skeletal muscle2021

    • Author(s)
      Egami Riku、Kokaji Toshiya、Hatano Atsushi、et al.
    • Journal Title

      iScience

      Volume: 24 Issue: 3 Pages: 102217-102217

    • DOI

      10.1016/j.isci.2021.102217

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Stability of RNA sequences derived from the coronavirus genome in human cells2020

    • Author(s)
      Wakida Hiroyasu、Kawata Kentaro、Yamaji Yuta、Hattori Emi、Tsuchiya Takaho、Wada Youichiro、Ozaki Haruka、Akimitsu Nobuyoshi
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 527 Issue: 4 Pages: 993-999

    • DOI

      10.1016/j.bbrc.2020.05.008

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Transomics analysis reveals allosteric and gene regulation axes for altered hepatic glucose-responsive metabolism in obesity2020

    • Author(s)
      Kokaji Toshiya、Hatano Atsushi、Ito Yuki、et al.
    • Journal Title

      Science Signaling

      Volume: 13 Issue: 660 Pages: 1236-1236

    • DOI

      10.1126/scisignal.aaz1236

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] MOCCSプロファイルで明らかにする、転写因子認識配列の細胞型特異性とヒト一塩基多型が 転写因子結合へ与える影響2022

    • Author(s)
      Saeko Tahara, Takaho Tsuchiya, Hirotaka Matsumoto and Haruka Ozaki
    • Organizer
      2022年日本バイオインフォマティクス学会年会・第11回生命医薬情報学連合大会(IIBMP2022)
    • Related Report
      2022 Research-status Report
  • [Presentation] MOCCS-DB: ヒト転写因子認識配列の多様性データベース2022

    • Author(s)
      田原 沙絵子,土屋 貴穂,松澤 亮輔,尾崎 遼
    • Organizer
      トーゴーの日シンポジウム2022
    • Related Report
      2022 Research-status Report
  • [Presentation] Predicting SNPs' effects on transcriptional factor binding and cell-type specificity using a crowd of ChIP-seq data2022

    • Author(s)
      田原沙絵子, 土屋貴穂, 松本拡高, 尾崎遼
    • Organizer
      日本人類遺伝学会第67回大会
    • Related Report
      2022 Research-status Report
  • [Presentation] Cell-Cell PLS regression analysis reveals cell-type specific spatial dependency of transcriptome in single cells2021

    • Author(s)
      Takaho Tsuchiya and Haruka Ozaki
    • Organizer
      日本バイオインフォマティクス学会 2021年年会 第10回生命医薬情報学連合大会(IBMP2021)
    • Related Report
      2021 Research-status Report
  • [Presentation] CCPLS reveals cell-type specific spatial dependence of transcriptome in single cells2021

    • Author(s)
      Takaho Tsuchiya and Haruka Ozaki
    • Organizer
      CREST BioDX Symposium 2021
    • Related Report
      2021 Research-status Report
  • [Presentation] k-mer profile analysis clarifies cell-type specific TF binding landscape in human2021

    • Author(s)
      Saeko Tahara, Takaho Tsuchiya and Haruka Ozaki
    • Organizer
      日本バイオインフォマティクス学会 2021年年会 第10回生命医薬情報学連合大会(IBMP2021)
    • Related Report
      2021 Research-status Report
  • [Presentation] CellCellTopic:cell-cell interaction analysis by Dirichlet multinomial regression topic modeling2020

    • Author(s)
      Takaho Tsuchiya and Haruka Ozaki
    • Organizer
      日本バイオインフォマティクス学会 2020年年会 第9回生命医薬情報学連合大会(IBMP2020)
    • Related Report
      2020 Research-status Report
  • [Remarks] TRIOS

    • URL

      https://trios.tsukuba.ac.jp/researcher/0000004298

    • Related Report
      2023 Annual Research Report 2022 Research-status Report

URL: 

Published: 2020-04-28   Modified: 2025-01-30  

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