An analysis of the sensitivity of proteogenomic mapping of somatic mutations and novel splicing events in cancer

Kelly V. Ruggles, Zuojian Tang, Xuya Wang, Himanshu Grover, Manor Askenazi, Jennifer Teubl, Song Cao, Michael D. McLellan, Karl R. Clauser, David L. Tabb, Philipp Mertins, Robbert Slebos, Petra Erdmann-Gilmore, Shunqiang Li, Harsha P. Gunawardena, Ling Xie, Tao Liu, Jian Ying Zhou, Shisheng Sun, Katherine A. Hoadley & 18 others Charles M. Perou, Xian Chen, Sherri R. Davies, Christopher A. Maher, Christopher R. Kinsinger, Karen D. Rodland, Hui Zhang, Zhen Zhang, Li Ding, R. Reid Townsend, Henry Rodriguez, Daniel Wan-Yui Chan, Richard D. Smith, Daniel C. Liebler, Steven A. Carr, Samuel Payne, Matthew J. Ellis, David Fenyo

Research output: Contribution to journalArticle

Abstract

Improvements in mass spectrometry (MS)-based peptide sequencing provide a new opportunity to determine whether polymorphisms, mutations, and splice variants identified in cancer cells are translated. Herein, we apply a proteogenomic data integration tool (QUILTS) to illustrate protein variant discovery using whole genome, whole transcriptome, and global proteome datasets generated from a pair of luminal and basal-like breast-cancer-patient-derived xenografts (PDX). The sensitivity of proteogenomic analysis for singe nucleotide variant (SNV) expression and novel splice junction (NSJ) detection was probed using multiple MS/MS sample process replicates defined here as an independent tandem MS experiment using identical sample material. Despite analysis of over 30 sample process replicates, only about 10% of SNVs (somatic and germline) detected by both DNA and RNA sequencing were observed as peptides. An even smaller proportion of peptides corresponding to NSJ observed by RNA sequencing were detected (

Original languageEnglish (US)
Pages (from-to)1060-1071
Number of pages12
JournalMolecular and Cellular Proteomics
Volume15
Issue number3
DOIs
StatePublished - Mar 1 2016

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RNA Sequence Analysis
Mass spectrometry
Tandem Mass Spectrometry
Peptides
Mutation
Neoplasms
RNA
Proteome
DNA Sequence Analysis
Transcriptome
Heterografts
Data integration
Mass Spectrometry
Nucleotides
Polymorphism
Genome
Breast Neoplasms
Genes
Cells
Proteogenomics

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Analytical Chemistry

Cite this

An analysis of the sensitivity of proteogenomic mapping of somatic mutations and novel splicing events in cancer. / Ruggles, Kelly V.; Tang, Zuojian; Wang, Xuya; Grover, Himanshu; Askenazi, Manor; Teubl, Jennifer; Cao, Song; McLellan, Michael D.; Clauser, Karl R.; Tabb, David L.; Mertins, Philipp; Slebos, Robbert; Erdmann-Gilmore, Petra; Li, Shunqiang; Gunawardena, Harsha P.; Xie, Ling; Liu, Tao; Zhou, Jian Ying; Sun, Shisheng; Hoadley, Katherine A.; Perou, Charles M.; Chen, Xian; Davies, Sherri R.; Maher, Christopher A.; Kinsinger, Christopher R.; Rodland, Karen D.; Zhang, Hui; Zhang, Zhen; Ding, Li; Townsend, R. Reid; Rodriguez, Henry; Chan, Daniel Wan-Yui; Smith, Richard D.; Liebler, Daniel C.; Carr, Steven A.; Payne, Samuel; Ellis, Matthew J.; Fenyo, David.

In: Molecular and Cellular Proteomics, Vol. 15, No. 3, 01.03.2016, p. 1060-1071.

Research output: Contribution to journalArticle

Ruggles, KV, Tang, Z, Wang, X, Grover, H, Askenazi, M, Teubl, J, Cao, S, McLellan, MD, Clauser, KR, Tabb, DL, Mertins, P, Slebos, R, Erdmann-Gilmore, P, Li, S, Gunawardena, HP, Xie, L, Liu, T, Zhou, JY, Sun, S, Hoadley, KA, Perou, CM, Chen, X, Davies, SR, Maher, CA, Kinsinger, CR, Rodland, KD, Zhang, H, Zhang, Z, Ding, L, Townsend, RR, Rodriguez, H, Chan, DW-Y, Smith, RD, Liebler, DC, Carr, SA, Payne, S, Ellis, MJ & Fenyo, D 2016, 'An analysis of the sensitivity of proteogenomic mapping of somatic mutations and novel splicing events in cancer', Molecular and Cellular Proteomics, vol. 15, no. 3, pp. 1060-1071. https://doi.org/10.1074/mcp.M115.056226
Ruggles, Kelly V. ; Tang, Zuojian ; Wang, Xuya ; Grover, Himanshu ; Askenazi, Manor ; Teubl, Jennifer ; Cao, Song ; McLellan, Michael D. ; Clauser, Karl R. ; Tabb, David L. ; Mertins, Philipp ; Slebos, Robbert ; Erdmann-Gilmore, Petra ; Li, Shunqiang ; Gunawardena, Harsha P. ; Xie, Ling ; Liu, Tao ; Zhou, Jian Ying ; Sun, Shisheng ; Hoadley, Katherine A. ; Perou, Charles M. ; Chen, Xian ; Davies, Sherri R. ; Maher, Christopher A. ; Kinsinger, Christopher R. ; Rodland, Karen D. ; Zhang, Hui ; Zhang, Zhen ; Ding, Li ; Townsend, R. Reid ; Rodriguez, Henry ; Chan, Daniel Wan-Yui ; Smith, Richard D. ; Liebler, Daniel C. ; Carr, Steven A. ; Payne, Samuel ; Ellis, Matthew J. ; Fenyo, David. / An analysis of the sensitivity of proteogenomic mapping of somatic mutations and novel splicing events in cancer. In: Molecular and Cellular Proteomics. 2016 ; Vol. 15, No. 3. pp. 1060-1071.
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