4.8 Article

Pan-cancer proteomic map of 949 human cell lines

Journal

CANCER CELL
Volume 40, Issue 8, Pages 835-+

Publisher

CELL PRESS
DOI: 10.1016/j.ccell.2022.06.010

Keywords

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Funding

  1. Australian Cancer Research Foundation
  2. Cancer Institute New South Wales (NSW) [2017/TPG001, REG171150]
  3. NSW Ministry of Health [CMP-01]
  4. University of Sydney
  5. Cancer Council NSW [IG 18-01]
  6. Ian Potter Foundation
  7. Medical Research Future Fund (MRFF-PD)
  8. National Health and Medical Research Council (NHMRC) of Australia
  9. European Union [GNT1170739, 826121]
  10. National Breast Cancer Foundation [IIRS-18-164]
  11. Children's Medical Research Institute
  12. U.S. National Cancer Institute's International Cancer Proteogenomics Consortium (ICPC)
  13. NHMRC [GNT1138536, GNT1137064]
  14. INESC-ID multi-annual funding [UIDB/50021/2020]
  15. Wellcome Trust [206194]

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The study analyzes the proteomes of multiple cancer cell lines through mass spectrometry and reveals thousands of cancer protein biomarkers that are not significant at the transcript level, demonstrating that the proteome has predictive power for drug response similar to the transcriptome.
The proteome provides unique insights into disease biology beyond the genome and transcriptome. A lack of large proteomic datasets has restricted the identification of new cancer biomarkers. Here, proteomes of 949 cancer cell lines across 28 tissue types are analyzed by mass spectrometry. Deploying a workflow to quantify 8,498 proteins, these data capture evidence of cell-type and post-transcriptional modifications. Integrating multi-omics, drug response, and CRISPR-Cas9 gene essentiality screens with a deep learning-based pipeline reveals thousands of protein biomarkers of cancer vulnerabilities that are not significant at the transcript level. The power of the proteome to predict drug response is very similar to that of the transcriptome. Further, random downsampling to only 1,500 proteins has limited impact on predictive power, consistent with protein networks being highly connected and co-regulated. This pan-cancer proteomic map (ProCan-DepMapSanger) is a comprehensive resource available at https://cellmodelpassports.sanger.ac.uk.

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