Genomic Determinants of Protein Abundance Variation in Colorectal Cancer Cells.
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Authors
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
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
Document Type
Journal Article
Date
2017-08-29
Date Accepted
2017-07-24
Abstract
Assessing the impact of genomic alterations on protein networks is fundamental in identifying the mechanisms that shape cancer heterogeneity. We have used isobaric labeling 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.
Citation
Cell reports, 2017, 20 (9), pp. 2201 - 2214
Source Title
Publisher
CELL PRESS
ISSN
2211-1247
eISSN
2211-1247
Collections
Research Team
Functional Proteomics Group