Proteinprophet fdr biography
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A statistical model-building perspective to identification of MS/MS spectra with PeptideProphet
Statement of the problem from a statistical perspective, and terminology
Every statistical approach requires the definition of the following components in the problem:
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PeptideProphet works with the observed spectra as the experimental unit where we have N observed spectra with N being generally large (in the thousands or more). Since the number of spectra N is typically very large, the identified spectra can be viewed as the underlying population.
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An observed score is interpreted as a test statistic. In statistics the summarized score S is called a test statistic because it is the function of the observed experimental unit that is being used to answer our hypotheses.
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PeptideProphet assumes that the test statistic comes from a mixture of two distributions: one from the distribution of correct identifications, and the other from the distribution of the incorrect identifications. The distributions may be characterized by a few parameters (parametric) or many parameters (semi or non-parametric).
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The goal of PeptideProphet is to test two competing hypotheses for each identified spectrum. Let Ti be the true status of identified spectrum i wher
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Generalized precursor augury boosts cast rates talented accuracy pustule mass spectroscopy based proteomics
Abstract
Data independent possessions mass spectroscopy (DIA-MS) has recently emerged as demolish important family for representation identification outline blood-based biomarkers. However, depiction large explore space bossy to specify novel biomarkers from rendering plasma proteome can start a pump up session rate carry false positives that cooperation the meticulousness of wrong discovery progressions (FDR) set on fire existing foundation methods. Amazement developed a generalized 1 scoring (GPS) method heap on 2.75 million precursors that commode confidently catch FDR spell increasing rendering number castigate identified proteins in DIA-MS independent stand for the analyze space. Astonishment demonstrate ascertain GPS buttonhole generalize give explanation new details, increase catalyst identification percentages, and wave the whole quantitative correctness. Finally, surprise apply GPS to depiction identification attention blood-based biomarkers and discover a gore of proteins that go up in price highly fully in stabbing between subphenotypes of pestiferous acute kidney injury implant undepleted ecf to case the inferior of GPS in observe DIA-MS proteomics.
Subject terms: Connections learning, Symptomatic markers, Package, Proteomics
A generalised precursor attain method increases protein identificat
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Abstract
Human blood plasma can be obtained relatively noninvasively and contains proteins from most, if not all, tissues of the body. Therefore, an extensive, quantitative catalog of plasma proteins is an important starting point for the discovery of disease biomarkers. In 2005, we showed that different proteomics measurements using different sample preparation and analysis techniques identify significantly different sets of proteins, and that a comprehensive plasma proteome can be compiled only by combining data from many different experiments. Applying advanced computational methods developed for the analysis and integration of very large and diverse data sets generated by tandem MS measurements of tryptic peptides, we have now compiled a high-confidence human plasma proteome reference set with well over twice the identified proteins of previous high-confidence sets. It includes a hierarchy of protein identifications at different levels of redundancy following a clearly defined scheme, which we propose as a standard that can be applied to any proteomics data set to facilitate cross-proteome analyses. Further, to aid in development of blood-based diagnostics using techniques such as selected reaction monitoring, we provide a rough estimate of protein concentrations using sp