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Query: UMLS:C0476089 (endometrial cancer)
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Discovering driver pathways is an essential task to understand the pathogenesis of cancer and to design precise treatments for cancer patients. Increasing evidences have been indicating that multiple pathways often function cooperatively in carcinogenesis. In this study, we propose an approach called CDPath to discover cooperative driver pathways. CDPath firstly uses Integer Linear Programming to explore driver core modules from mutation profiles by enforcing co-occurrence and functional interaction relations between modules, and by maximizing the mutual exclusivity and coverage within modules. Next, to enforce cooperation of pathways and help the follow-up exact cooperative driver pathways discovery, it performs Markov clustering on pathway-pathway interaction network to cluster pathways. After that, it identifies pathways in different modules but in the same clusters as cooperative driver pathways. We apply CDPath on two TCGA datasets: breast cancer (BRCA) and endometrial cancer (UCEC). The results show that CDPath can identify known (i.e., TP53) and potential driver genes (i.e., SPTBN2). In addition, the identified cooperative driver pathways are related with the target cancer, and they are involved with carcinogenesis and several key biological processes. CDPath can uncover more potential biological associations between pathways (over 100%) and more cooperative driver pathways (over 200%) than competitive approaches.
IEEE/ACM Trans Comput Biol Bioinform 2019 Oct 01
PMID:CDPath: Cooperative driver pathways discovery using integer linear programming and Markov clustering. 3158 Oct 94

The remarkable growth of multi-platform genomic profiles has led to the challenge of multiomics data integration. In this study, we present a novel network-based multiomics clustering founded on the Wasserstein distance from optimal mass transport. This distance has many important geometric properties making it a suitable choice for application in machine learning and clustering. Our proposed method of aggregating multiomics and Wasserstein distance clustering (aWCluster) is applied to breast carcinoma as well as bladder carcinoma, colorectal adenocarcinoma, renal carcinoma, lung non-small cell adenocarcinoma, and endometrial carcinoma from The Cancer Genome Atlas project. Subtypes were characterized by the concordant effect of mRNA expression, DNA copy number alteration, and DNA methylation of genes and their neighbors in the interaction network. aWCluster successfully clusters all cancer types into classes with significantly different survival rates. Also, a gene ontology enrichment analysis of significant genes in the low survival subgroup of breast cancer leads to the well-known phenomenon of tumor hypoxia and the transcription factor ETS1 whose expression is induced by hypoxia. We believe aWCluster has the potential to discover novel subtypes and biomarkers by accentuating the genes that have concordant multiomics measurements in their interaction network, which are challenging to find without the network inference or with single omics analysis.
IEEE/ACM Trans Comput Biol Bioinform 2020 Nov 23
PMID:aWCluster: A Novel Integrative Network-based Clustering of Multiomics for Subtype Analysis of Cancer Data. 3322 52