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CDPath: Cooperative Driver Pathways Discovery Using Integer Linear Programming and Markov Clustering | IEEE Journals & Magazine | IEEE Xplore

CDPath: Cooperative Driver Pathways Discovery Using Integer Linear Programming and Markov Clustering


Abstract:

Discovering driver pathways is an essential task to understand the pathogenesis of cancer and to design precise treatments for cancer patients. Increasing evidences have ...Show More

Abstract:

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 first 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 percent) and more cooperative driver pathways (over 200 percent) than competitive approaches. The demo codes of CDPath are available at http://mlda.swu.edu.cn/codes.php?name=CDPath.
Published in: IEEE/ACM Transactions on Computational Biology and Bioinformatics ( Volume: 18, Issue: 4, 01 July-Aug. 2021)
Page(s): 1384 - 1395
Date of Publication: 01 October 2019

ISSN Information:

PubMed ID: 31581094

Funding Agency:


References

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