Proteogenomic analysis of Candida glabrata using high resolution mass spectrometry

J Proteome Res. 2012 Jan 1;11(1):247-60. doi: 10.1021/pr200827k. Epub 2011 Dec 13.

Abstract

Candida glabrata is a common opportunistic human pathogen leading to significant mortality in immunosuppressed and immunodeficient individuals. We carried out proteomic analysis of C. glabrata using high resolution Fourier transform mass spectrometry with MS resolution of 60,000 and MS/MS resolution of 7500. On the basis of 32,453 unique peptides identified from 118,815 peptide-spectrum matches, we validated 4421 of the 5283 predicted protein-coding genes (83%) in the C. glabrata genome. Further, searching the tandem mass spectra against a six frame translated genome database of C. glabrata resulted in identification of 11 novel protein coding genes and correction of gene boundaries for 14 predicted gene models. A subset of novel protein-coding genes and corrected gene models were validated at the transcript level by RT-PCR and sequencing. Our study illustrates how proteogenomic analysis enabled by high resolution mass spectrometry can enrich genome annotation and should be an integral part of ongoing genome sequencing and annotation efforts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Candida glabrata / genetics
  • Candida glabrata / metabolism*
  • Codon, Initiator
  • Fourier Analysis
  • Fungal Proteins / chemistry
  • Fungal Proteins / genetics*
  • Fungal Proteins / metabolism
  • Gene Expression
  • Molecular Sequence Annotation
  • Molecular Sequence Data
  • Peptide Fragments / chemistry
  • Peptide Mapping
  • Proteome / chemistry
  • Proteome / genetics*
  • Proteome / metabolism
  • Proteomics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tandem Mass Spectrometry

Substances

  • Codon, Initiator
  • Fungal Proteins
  • Peptide Fragments
  • Proteome