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A computational tool to detect and avoid redundancy in selected reaction monitoring.

Type Information
Nr 30 (Research article)
Authors Rost, Hannes; Malmström, Lars; Aebersold, Ruedi
Title A computational tool to detect and avoid redundancy in selected reaction monitoring.
Journal Mol Cell Proteomics (2012) 11 540-9
DOI 10.1074/mcp.M111.013045
Citations 88 citations (journal impact: 7.25)
Abstract SelectedMultiple reaction monitoring SRMMRM has become an invaluable tool for targeted quantitative proteomic analyses but its application can be compromised by non-optimal selection of transitions. In particular complex backgrounds may cause ambiguities in SRM measurement results because peptides with interfering transitions similar to those of the target peptide may be present in the sample. Here we developed a computer program the SRMCollider that calculates non-redundant theoretical SRM-assays also known as unique ion signatures UIS for a given proteomic background. We show theoretically that UIS of three transitions suffice to conclusively identify 90 of all yeast peptides and 85 of all human peptides. Using predicted retention times the SRMCollider also simulates time-scheduled SRM acquisition - which reduces the number of interferences to consider and leads to fewer transitions necessary to construct an assay. By integrating experimental fragment ion intensities from large scale proteome synthesis efforts SRMAtlas with the information content based UIS we combine two orthogonal approaches to create high-quality SRM-assays ready to be deployed. We provide a user-friendly open-source implementation of an algorithm to calculate UIS of any order that can be accessed online at httpwww.srmcollider.org to find interfering transitions. Finally our tool can also simulate the specificity of novel data-independent MS-acquisition methods in Q1-Q3 space. This allows us to predict parameters for these methods that deliver a specificity comparable to that of SRM.Using SRM interference information in addition to other sources of information can increase the confidence in an SRM measurement. We expect that the consideration of information content will become a standard step in SRM-assay design and analysis facilitated by the SRMCollider.
Synopsis This paper presents a tool which can evaluate potential collisions between SRM assays.