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Solution to Statistical Challenges in Proteomics Is More Statistics, Not Less
KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.ORCID iD: 0000-0001-5689-9797
2015 (English)In: Journal of Proteome Research, ISSN 1535-3893, E-ISSN 1535-3907, Vol. 14, no 10, 4099-4103 p.Article in journal, Editorial material (Other academic) Published
Abstract [en]

In any high-throughput scientific study, it is often essential to estimate the percent of findings that are actually incorrect. This percentage is called the false discovery rate (abbreviated "FDR"), and it is an invariant (albeit, often unknown) quantity for any well-formed study. In proteomics, it has become common practice to incorrectly conflate the protein FDR (the percent of identified proteins that are actually absent) with protein-level target-decoy, a particular method for estimating the protein-level FDR. In this manner, the challenges of one approach have been used as the basis for an argument that the field should abstain from protein-level FDR analysis altogether or even the suggestion that the very notion of a protein FDR is flawed. As we demonstrate in simple but accurate simulations, not only is the protein-level FDR an invariant concept, when analyzing large data sets, the failure to properly acknowledge it or to correct for multiple testing can result in large, unrecognized errors, whereby thousands of absent proteins (and, potentially every protein in the FASTA database being considered) can be incorrectly identified.

Place, publisher, year, edition, pages
[Serang, Oliver] Free Univ Berlin, Dept Informat, D-14195 Berlin, Germany. [Serang, Oliver] Leibniz Inst Freshwater Ecol & Inland Fisheries I, D-12587 Berlin, Germany. [Kall, Lukas] Royal Inst Technol KTH, Sch Biotechnol, Sci Life Lab, SE-17121 Solna, Sweden., 2015. Vol. 14, no 10, 4099-4103 p.
Keyword [en]
protein identification, false discovery rate (FDR), simulation, multiple testing human proteome, statistics
National Category
Biochemistry and Molecular Biology
URN: urn:nbn:se:kth:diva-176352DOI: 10.1021/acs.jproteome.5b00568ISI: 000362385100001PubMedID: 26257019ScopusID: 2-s2.0-84942905791OAI: diva2:867873

QC 20151106

Available from: 2015-11-06 Created: 2015-11-03 Last updated: 2015-11-06Bibliographically approved

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