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Computational discovery of pathway-level genetic vulnerabilities in non-small-cell lung cancer.

Authors
 Jonathan H. Young  ;  Michael Peyton  ;  Hyun Seok Kim  ;  Elizabeth McMillan  ;  John D. Minna  ;  Michael A. White  ;  Edward M. Marcotte 
Citation
 BIOINFORMATICS, Vol.32(9) : 1373-1379, 2016 
Journal Title
 BIOINFORMATICS 
ISSN
 1367-4803 
Issue Date
2016
MeSH
Algorithms ; Carcinoma, Non-Small-Cell Lung/genetics* ; Cluster Analysis ; DNA, Neoplasm* ; Gene Expression Regulation, Neoplastic ; Humans ; Lung Neoplasms/genetics*
Abstract
MOTIVATION: Novel approaches are needed for discovery of targeted therapies for non-small-cell lung cancer (NSCLC) that are specific to certain patients. Whole genome RNAi screening of lung cancer cell lines provides an ideal source for determining candidate drug targets. RESULTS: Unsupervised learning algorithms uncovered patterns of differential vulnerability across lung cancer cell lines to loss of functionally related genes. Such genetic vulnerabilities represent candidate targets for therapy and are found to be involved in splicing, translation and protein folding. In particular, many NSCLC cell lines were especially sensitive to the loss of components of the LSm2-8 protein complex or the CCT/TRiC chaperonin. Different vulnerabilities were also found for different cell line subgroups. Furthermore, the predicted vulnerability of a single adenocarcinoma cell line to loss of the Wnt pathway was experimentally validated with screening of small-molecule Wnt inhibitors against an extensive cell line panel. AVAILABILITY AND IMPLEMENTATION: The clustering algorithm is implemented in Python and is freely available at https://bitbucket.org/youngjh/nsclc_paper CONTACT: marcotte@icmb.utexas.edu or jon.young@utexas.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
Files in This Item:
T201601351.pdf Download
DOI
10.1093/bioinformatics/btw010
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
Yonsei Authors
Kim, Hyun Seok(김현석) ORCID logo https://orcid.org/0000-0003-4498-8690
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/146810
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