Interpretation of Shotgun Proteomic Data

By Alexey I. Nesvizhskii, R. Aebersold. Molecular & Cellular Proteomics, 2005

612 citations recorded by the source corpus.

The shotgun proteomic strategy based on digesting proteins into peptides and sequencing them using tandem mass spectrometry and automated database searching has become the method of choice for identifying proteins in most large scale studies. However, the peptide-centric nature of shotgun proteomics complicates the analysis and biological interpretation of the data especially in the case of higher eukaryote organisms. The same peptide sequence can be present in multiple different proteins or protein isoforms. Such shared peptides therefore can lead to ambiguities in determining the identities of sample proteins. In this article we illustrate the difficulties of interpreting shotgun proteomic data and discuss the need for common nomenclature and transparent informatic approaches. We also discuss related issues such as the state of protein sequence databases and their role in shotgun proteomic analysis, interpretation of relative peptide quantification data in the presence of multiple protein isoforms, the integration of proteomic and transcriptional data, and the development of a computational infrastructure for the integration of multiple diverse datasets.

Subfields: Molecular Biology, Spectroscopy

View Paper: https://www.semanticscholar.org/paper/b32844c0c81d1d6552b825e818ba1c915dedc285

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Citations in the corpus

iProphet: Multi-level Integrative Analysis of Shotgun Proteomic Data Improves Peptide and Protein Identification Rates and Error Estimates* (2011, background): “Another important challenge—dealing with shared peptides and creation of proteins groups for final presentation (54)—continues to be handled by ProteinProphet and thus is not discussed here in detail.”
Significance Analysis of Spectral Count Data in Label-free Shotgun Proteomics*S (2008, background): “Finally the protein inference problem of shotgun proteomics should not be overlooked because it also affects quantification (38).”
Mass spectrometry–based proteomics turns quantitative (2005, background): “This is a recognized problem in protein identification, as peptides unique to an isoform may or may not have been identifie”