4 years ago

Genomic Determinants of Protein Abundance Variation in Colorectal Cancer Cells

Genomic Determinants of Protein Abundance Variation in Colorectal Cancer Cells
Julio Saez-Rodriguez, Lodewyk Wessels, David J. Adams, Oliver Stegle, Lu Yu, Stacey Price, Michael Schubert, Emanuel Gonçalves, Ultan McDermott, Mi Yang, Clara Alsinet, Mercedes Pardo, Justin Guinney, Jyoti S. Choudhary, Alvis Brazma, Pedro Beltrao, Magali Michaut, Nanne Aben, Rodrigo Dienstmann, Martin Del Castillo Velasco-Herrera, Steven P. Williams, James C. Wright, Theodoros I. Roumeliotis, Fatemeh Zamanzad Ghavidel


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.

Publisher URL: http://www.cell.com/cell-reports/fulltext/S2211-1247(17)31100-2

DOI: 10.1016/j.celrep.2017.08.010

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.