Characterization of Proteoforms with Unknown Post-translational Modifications Using the MIScore.
Various proteoforms may be generated from a single gene due to primary structure alterations (PSAs) such as genetic variations, alternative splicing, and post-translational modifications (PTMs). Top-down mass spectrometry is capable of analyzing intact proteins and identifying patterns of multiple PSAs, making it the method of choice for studying complex proteoforms. In top-down proteomics, proteoform identification is often performed by searching tandem mass spectra against a protein sequence database that contains only one reference protein sequence for each gene or transcript variant in a proteome. Because of the incompleteness of the protein database, an identified proteoform may contain unknown PSAs compared with the reference sequence. Proteoform characterization is to identify and localize PSAs in a proteoform. Although many software tools have been proposed for proteoform identification by top-down mass spectrometry, the characterization of proteoforms in identified proteoform-spectrum matches still relies mainly on manual annotation. We propose to use the Modification Identification Score (MIScore), which is based on Bayesian models, to automatically identify and localize PTMs in proteoforms. Experiments showed that the MIScore is accurate in identifying and localizing one or two modifications.
Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis , Indianapolis, Indiana 46202, United States.
Qiang
Q
Kou
Department of Computer Science, Montana State University , Bozeman, Montana 59717, United States.
Binhai
B
Zhu
Department of Chemistry and Biochemistry, Univeristy of Oklahoma , Norman, Oklahoma 73019-5251, United States.
Si
S
Wu
Charles
C
Ansong
Nikola
N
Tolić
Ljiljana
L
Paša-Tolić
Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis , Indianapolis, Indiana 46202, United States.|Center for Computational Biology and Bioinformatics, Indiana University School of Medicine , Indianapolis, Indiana 46202-5122, United States.
Xiaowen
X
Liu
D001499:Bayes Theorem; D004926:Escherichia coli / Q000737:chemistry; D011499:Protein Processing, Post-Translational; D020543:Proteome / Q000032:analysis*; D040901:Proteomics / Q000379:methods*; D012486:Salmonella typhimurium / Q000737:chemistry; D012984:Software; D053719:Tandem Mass Spectrometry
D020543:Proteome
post-translational modification; proteoform