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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

classCleaner: A Quantitative Method for Validating Peptide Identification in LC-MS/MS Workflows

Key, Melissa Chester 05 1900 (has links)
Indiana University-Purdue University Indianapolis (IUPUI) / Because label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS) shotgun proteomics infers the peptide sequence of each measurement, there is inherent uncertainty in the identity of each peptide and its originating protein. Removing misidentified peptides can improve the accuracy and power of downstream analyses when differences between proteins are of primary interest. In this dissertation I present classCleaner, a novel algorithm designed to identify misidentified peptides from each protein using the available quantitative data. The algorithm is based on the idea that distances between peptides belonging to the same protein are stochastically smaller than those between peptides in different proteins. The method first determines a threshold based on the estimated distribution of these two groups of distances. This is used to create a decision rule for each peptide based on counting the number of within-protein distances smaller than the threshold. Using simulated data, I show that classCleaner always reduces the proportion of misidentified peptides, with better results for larger proteins (by number of constituent peptides), smaller inherent misidentification rates, and larger sample sizes. ClassCleaner is also applied to a LC-MS/MS proteomics data set and the Congressional Voting Records data set from the UCI machine learning repository. The later is used to demonstrate that the algorithm is not specific to proteomics.

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