Integrative pathway enrichment analysis of multivariate omics data.
Authors
Paczkowska, Marta
Barenboim, Jonathan
Sintupisut, Nardnisa
Fox, Natalie S
Zhu, Helen
Abd-Rabbo, Diala
Mee, Miles W
PCAWG Drivers and Functional Interpretation Working Group
PCAWG Consortium
Publication Date
2020-02-05Journal Title
Nat Commun
ISSN
2041-1723
Publisher
Springer Science and Business Media LLC
Volume
11
Issue
1
Language
en
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Paczkowska, M., Barenboim, J., Sintupisut, N., Fox, N. S., Zhu, H., Abd-Rabbo, D., Mee, M. W., et al. (2020). Integrative pathway enrichment analysis of multivariate omics data.. Nat Commun, 11 (1) https://doi.org/10.1038/s41467-019-13983-9
Description
Funder: BioTalent Canada Student Internship
Funder: Canadian Institutes of Health Research (CIHR) Canadian Graduate Scholarship
Funder: Ontario Institute for Cancer Research (OICR) Investigator Awards provided by the Government of Ontario; Terry Fox Research Institute (TFRI) and Canadian Institutes of Health Research (CIHR) New Investigator Awards.
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.
Keywords
Article, /631/67/69, /631/114/2401, /631/114/2403, /45, /49, /38, /38/91, /38/39, /139, /119, article
Identifiers
s41467-019-13983-9, 13983
External DOI: https://doi.org/10.1038/s41467-019-13983-9
This record's URL: https://www.repository.cam.ac.uk/handle/1810/317169
Rights
Attribution 4.0 International (CC BY 4.0)
Licence URL: https://creativecommons.org/licenses/by/4.0/
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