Assessing the impact of genomic alterations on protein networks is fundamental in identifying the mechanisms that shape cancer heterogeneity. We have used isobaric labelling to characterize the proteomic landscapes of 50 colorectal cancer cell lines and to decipher the functional consequences of somatic genomic variants. The robust quantification of over 9,000 proteins and 11,000 phosphopeptides on average, enabled the de novo construction of a functional protein correlation network which ultimately exposed the collateral effects of mutations on protein complexes. CRISPR-cas9 deletion of key chromatin modifiers confirmed that the consequences of genomic alterations can propagate through protein interactions in a transcript-independent manner. Lastly, we leveraged the quantified proteome to perform unsupervised classification of the cell lines and to build predictive models of drug response in colorectal cancer. Overall, we provide a deep integrative view of the functional network and the molecular structure underlying the heterogeneity of colorectal cancer cells.
[dataset license: CC0 1.0 Universal (CC0 1.0)]
Keywords: Proteomics ; TMT ; protein complexes ; networks ; phosphorylation ; mutations ; CRISPR/cas9 ; colorectal cancer ; cell lines ; drug response
Principal Investigators: (in alphabetical order) |
Jyoti Choudhary, Wellcome Trust Sanger Institute, N/A |
Submitting User: | ccms |
Roumeliotis TI, Williams SP, Gonçalves E, Alsinet C, Del Castillo Velasco-Herrera M, Aben N, Ghavidel FZ, Michaut M, Schubert M, Price S, Wright JC, Yu L, Yang M, Dienstmann R, Guinney J, Beltrao P, Brazma A, Pardo M, Stegle O, Adams DJ, Wessels L, Saez-Rodriguez J, McDermott U, Choudhary JS.
Genomic Determinants of Protein Abundance Variation in Colorectal Cancer Cells.
Cell Rep. 2017 Aug 29;20(9):2201-2214.
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