title: IsoformResolver: A peptide-centric algorithm for protein inference.
abstract: When analyzing proteins in complex samples using tandem mass spectrometry of peptides generated by proteolysis, the inference of proteins can be ambiguous, even with well-validated peptides. Unresolved questions include whether to show all possible proteins vs a minimal list, what to do when proteins are inferred ambiguously, and how to quantify peptides that bridge multiple proteins, each with distinguishing evidence. Here we describe IsoformResolver, a peptide-centric protein inference algorithm that clusters proteins in two ways, one based on peptides experimentally identified from MS/MS spectra, and the other based on peptides derived from an in silico digest of the protein database. MS/MS-derived protein groups report minimal list proteins in the context of all possible proteins, without redundantly listing peptides. In silico-derived protein groups pull together functionally related proteins, providing stable identifiers. The peptide-centric grouping strategy used by IsoformResolver allows proteins to be displayed together when they share peptides in common, providing a comprehensive yet concise way to organize protein profiles. It also summarizes information on spectral counts and is especially useful for comparing results from multiple LC-MS/MS experiments. Finally, we examine the relatedness of proteins within IsoformResolver groups and compare its performance to other protein inference software.
authors: Department of Chemistry and Biochemistry, University of Colorado, Boulder, Colorado 80309-0215, USA.
authors: Karen
authors: K
authors: Meyer-Arendt
authors: William M
authors: WM
authors: Old
authors: Stephane
authors: S
authors: Houel
authors: Kutralanathan
authors: K
authors: Renganathan
authors: Brian
authors: B
authors: Eichelberger
authors: Katheryn A
authors: KA
authors: Resing
authors: Natalie G
authors: NG
authors: Ahn
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