TY  - JOUR
AU  - Paczkowska, Marta
AU  - Barenboim, Jonathan
AU  - Sintupisut, Nardnisa
AU  - Fox, Natalie S
AU  - Zhu, Helen
AU  - Abd-Rabbo, Diala
AU  - Mee, Miles W
AU  - Boutros, Paul C
AU  - Drivers, PCAWG
AU  - FunctionalInterpretationWorkingGroup
AU  - Reimand, Jüri
AU  - PCAWGConsortium
TI  - Integrative pathway enrichment analysis of multivariate omics data.
JO  - Nature Communications
VL  - 11
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Nature Publishing Group UK
M1  - DKFZ-2021-02567
SP  - 735
PY  - 2020
N1  - siehe Correction: DKFZ Autoren affiliiert im PCAWG Consortium: https://inrepo02.dkfz.de/record/212438   /  https://doi.org/10.1038/s41467-022-32342-9
AB  - 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.
KW  - Adenocarcinoma: genetics
KW  - Adenocarcinoma: metabolism
KW  - Apoptosis: genetics
KW  - Breast Neoplasms: genetics
KW  - Breast Neoplasms: immunology
KW  - Breast Neoplasms: metabolism
KW  - Breast Neoplasms: mortality
KW  - Chromatin Immunoprecipitation
KW  - Computational Biology: methods
KW  - Databases, Factual
KW  - Female
KW  - Gene Dosage
KW  - Gene Expression Profiling
KW  - Gene Regulatory Networks
KW  - Genomics: methods
KW  - Humans
KW  - Metabolic Networks and Pathways: genetics
KW  - Mutation
KW  - Neoplasms: genetics
KW  - Neoplasms: metabolism
KW  - Prognosis
KW  - Protein-Serine-Threonine Kinases: genetics
KW  - Protein-Serine-Threonine Kinases: metabolism
KW  - RNA, Messenger: genetics
KW  - Sequence Analysis, RNA
KW  - Signal Transduction
KW  - RNA, Messenger (NLM Chemicals)
KW  - Hippo protein, human (NLM Chemicals)
KW  - Protein-Serine-Threonine Kinases (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:32024846
C2  - pmc:PMC7002665
DO  - DOI:10.1038/s41467-019-13983-9
UR  - https://inrepo02.dkfz.de/record/177480
ER  -