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Integrative pathway enrichment analysis of multivariate omics data

Author

Listed:
  • Marta Paczkowska

    (Ontario Institute for Cancer Research)

  • Jonathan Barenboim

    (Ontario Institute for Cancer Research)

  • Nardnisa Sintupisut

    (Ontario Institute for Cancer Research)

  • Natalie S. Fox

    (Ontario Institute for Cancer Research
    University of Toronto)

  • Helen Zhu

    (Ontario Institute for Cancer Research
    University of Toronto)

  • Diala Abd-Rabbo

    (Ontario Institute for Cancer Research)

  • Miles W. Mee

    (Ontario Institute for Cancer Research)

  • Paul C. Boutros

    (Ontario Institute for Cancer Research
    University of Toronto
    University of Toronto
    University of California Los Angeles)

  • Jüri Reimand

    (Ontario Institute for Cancer Research
    University of Toronto)

Abstract

Multi-omics datasets represent distinct aspects of the central dogma of molecular biology. Such high-dimensional molecular profiles pose challenges to data interpretation and hypothesis generation. ActivePathways is an integrative method that discovers significantly enriched pathways across multiple datasets using statistical data fusion, rationalizes contributing evidence and highlights associated genes. As part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancers across 38 tumor types, we integrated genes with coding and non-coding mutations and revealed frequently mutated pathways and additional cancer genes with infrequent mutations. We also analyzed prognostic molecular pathways by integrating genomic and transcriptomic features of 1780 breast cancers and highlighted associations with immune response and anti-apoptotic signaling. Integration of ChIP-seq and RNA-seq data for master regulators of the Hippo pathway across normal human tissues identified processes of tissue regeneration and stem cell regulation. ActivePathways is a versatile method that improves systems-level understanding of cellular organization in health and disease through integration of multiple molecular datasets and pathway annotations.

Suggested Citation

  • Marta Paczkowska & Jonathan Barenboim & Nardnisa Sintupisut & Natalie S. Fox & Helen Zhu & Diala Abd-Rabbo & Miles W. Mee & Paul C. Boutros & Jüri Reimand, 2020. "Integrative pathway enrichment analysis of multivariate omics data," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-019-13983-9
    DOI: 10.1038/s41467-019-13983-9
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    1. Dzana Dervovic & Ahmad A. Malik & Edward L. Y. Chen & Masahiro Narimatsu & Nina Adler & Somaieh Afiuni-Zadeh & Dagmar Krenbek & Sebastien Martinez & Ricky Tsai & Jonathan Boucher & Jacob M. Berman & K, 2023. "In vivo CRISPR screens reveal Serpinb9 and Adam2 as regulators of immune therapy response in lung cancer," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    2. Luopin Wang & Aryamav Pattnaik & Subhransu Sekhar Sahoo & Ella G. Stone & Yuxin Zhuang & Annaleigh Benton & Md Tajmul & Srishti Chakravorty & Deepika Dhawan & My An Nguyen & Isabella Sirit & Kyle Mund, 2024. "Unbiased discovery of cancer pathways and therapeutics using Pathway Ensemble Tool and Benchmark," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    3. Michelle M. Kameda-Smith & Helen Zhu & En-Ching Luo & Yujin Suk & Agata Xella & Brian Yee & Chirayu Chokshi & Sansi Xing & Frederick Tan & Raymond G. Fox & Ashley A. Adile & David Bakhshinyan & Kevin , 2022. "Characterization of an RNA binding protein interactome reveals a context-specific post-transcriptional landscape of MYC-amplified medulloblastoma," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    4. Richard Culliford & Samuel E. D. Lawrence & Charlie Mills & Zayd Tippu & Daniel Chubb & Alex J. Cornish & Lisa Browning & Ben Kinnersley & Robert Bentham & Amit Sud & Husayn Pallikonda & Anna Frangou , 2024. "Whole genome sequencing refines stratification and therapy of patients with clear cell renal cell carcinoma," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    5. Chenqi Tang & Zetao Wang & Yuanhao Xie & Yang Fei & Junchao Luo & Canlong Wang & Yue Ying & Peiwen He & Ruojing Yan & Yangwu Chen & Jiayun Huang & Yiwen Xu & Zicheng Wang & Boon Chin Heng & Hengzhi Li, 2024. "Classification of distinct tendinopathy subtypes for precision therapeutics," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    6. Mykhaylo Slobodyanyuk & Alexander T. Bahcheli & Zoe P. Klein & Masroor Bayati & Lisa J. Strug & Jüri Reimand, 2024. "Directional integration and pathway enrichment analysis for multi-omics data," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    7. E. P. Tissink & A. A. Shadrin & D. Meer & N. Parker & G. Hindley & D. Roelfs & O. Frei & C. C. Fan & M. Nagel & T. Nærland & M. Budisteanu & S. Djurovic & L. T. Westlye & M. P. Heuvel & D. Posthuma & , 2024. "Abundant pleiotropy across neuroimaging modalities identified through a multivariate genome-wide association study," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

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