Integrative pathway enrichment analysis of multivariate omics data Journal Article

Authors: Paczkowska, M.; Barenboim, J.; Sintupisut, N.; Fox, N. S.; Zhu, H.; Abd-Rabbo, D.; Mee, M. W.; Boutros, P. C.; PCAWG Drivers and Functional Interpretation Working Group; Reimand, J.; & PCAWG Consortium
Contributors: Kahles, A.; Lehmann, K. V.; Liu, E. M.; Sander, C.
Article Title: Integrative pathway enrichment analysis of multivariate omics data
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. © 2020, The Author(s).
Keywords: gene expression; molecular analysis; genomics; multivariate analysis; data set; cancer
Journal Title: Nature Communications
Volume: 11
ISSN: 2041-1723
Publisher: Nature Publishing Group  
Date Published: 2020-02-05
Start Page: 735
Language: English
DOI: 10.1038/s41467-019-13983-9
PUBMED: 32024846
PROVIDER: scopus
PMCID: PMC7002665
Notes: Article -- Export Date: 2 March 2020 -- Source: Scopus
Citation Impact
MSK Authors
  1. Chris Sander
    204 Sander
  2. Andre Kahles
    25 Kahles
  3. Kjong Van Stephan Fritz Lehmann
    16 Lehmann
  4. Minwei Liu
    9 Liu