Mining gene functional networks to improve mass-spectrometry-based protein identification

Smriti R. Ramakrishnan, Christine Vogel, Taejoon Kwon, Luiz O. Penalva, Edward M. Marcotte, Daniel P. Miranker

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

Motivation: High-throughput protein identification experiments based on tandem mass spectrometry (MS/MS) often suffer from low sensitivity and low-confidence protein identifications. In a typical shotgun proteomics experiment, it is assumed that all proteins are equally likely to be present. However, there is often other evidence to suggest that a protein is present and confidence in individual protein identification can be updated accordingly. Results: We develop a method that analyzes MS/MS experiments in the larger context of the biological processes active in a cell. Our method, MSNet, improves protein identification in shotgun proteomics experiments by considering information on functional associations from a gene functional network. MSNet substantially increases the number of proteins identified in the sample at a given error rate. We identify 8-29% more proteins than the original MS experiment when applied to yeast grown in different experimental conditions analyzed on different MS/MS instruments, and 37% more proteins in a human sample. We validate up to 94% of our identifications in yeast by presence in ground-truth reference sets.

Original languageEnglish (US)
Pages (from-to)2955-2961
Number of pages7
JournalBioinformatics
Volume25
Issue number22
DOIs
StatePublished - Nov 15 2009

ASJC Scopus subject areas

  • Statistics and Probability
  • Biochemistry
  • Molecular Biology
  • Computer Science Applications
  • Computational Theory and Mathematics
  • Computational Mathematics

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