Reinspection of a clinical proteomics tumor analysis consortium (Cptac) dataset with cloud computing reveals abundant post-translational modifications and protein sequence variants

Amol Prakash, Lorne Taylor, Manu Varkey, Nate Hoxie, Yassene Mohammed, Young Ah Goo, Scott Peterman, Abhay Moghekar, Yuting Yuan, Trevor Glaros, Joel R. Steele, Pouya Faridi, Shashwati Parihari, Sanjeeva Srivastava, Joseph J. Otto, Julius O. Nyalwidhe, O. John Semmes, Michael F. Moran, Anil Madugundu, Dong Gi MunAkhilesh Pandey, Keira E. Mahoney, Jeffrey Shabanowitz, Satya Saxena, Benjamin C. Orsburn

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

The Clinical Proteomic Tumor Analysis Consortium (CPTAC) has provided some of the most in-depth analyses of the phenotypes of human tumors ever constructed. Today, the majority of proteomic data analysis is still performed using software housed on desktop computers which limits the number of sequence variants and post-translational modifications that can be considered. The original CPTAC studies limited the search for PTMs to only samples that were chemically enriched for those modified peptides. Similarly, the only sequence variants considered were those with strong evidence at the exon or transcript level. In this multi-institutional collaborative reanalysis, we utilized unbiased protein databases containing millions of human sequence variants in conjunction with hundreds of common post-translational modifications. Using these tools, we identified tens of thousands of high-confidence PTMs and sequence variants. We identified 4132 phosphorylated peptides in nonenriched samples, 93% of which were confirmed in the samples which were chemically enriched for phosphopeptides. In addition, our results also cover 90% of the high-confidence variants reported by the original proteogenomics study, without the need for sample specific next-generation sequencing. Finally, we report fivefold more somatic and germline variants that have an independent evidence at the peptide level, including mutations in ERRB2 and BCAS1. In this reanalysis of CPTAC proteomic data with cloud computing, we present an openly available and searchable web resource of the highest-coverage proteomic profiling of human tumors described to date.

Original languageEnglish
Article number5034
JournalCancers
Volume13
Issue number20
DOIs
StatePublished - Oct 1 2021

Keywords

  • CPTAC
  • Cancer
  • Cloud computing
  • Post-translational modifications
  • Proteogenomics
  • Proteomics
  • Tumor proteomics

Fingerprint

Dive into the research topics of 'Reinspection of a clinical proteomics tumor analysis consortium (Cptac) dataset with cloud computing reveals abundant post-translational modifications and protein sequence variants'. Together they form a unique fingerprint.

Cite this