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Proteoform identification and quantification based on alignment graphs

delete2025-01-09
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OA
AI
Z
Zhaohui Zhan
王
王路生 (Lusheng Wang) *
DOI:10.1093/bioinformatics/btaf007delete
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Abstract

Abstract

En 中文
Motivation Proteoforms are the different forms of a proteins generated from the genome with various sequence variations, splice isoforms, and post-translational modifications. Proteoforms regulate protein structures and functions. A single protein can have multiple proteoforms due to different modification sites. Proteoform identification is to find proteoforms of a given protein that best fits the input spectrum. Proteoform quantification is to find the corresponding abundances of different proteoforms for a specific protein.Results We proposed algorithms for proteoform identification and quantification based on the top-down tandem mass spectrum. In the combination alignments of the HomMTM spectrum and the reference protein, we need to give a correction of the mass for each matched peak within the pre-defined error range. After the correction, we impose that the mass between any two (not necessarily consecutive) matched nodes in the protein is identical to that of the corresponding two matched peaks in the HomMTM spectrum. We design a back-tracking graph to store such kind of information and find a combinatorial path (k paths) with the minimum sum of peak intensity error in this back-tracking graph. The obtained alignment can also show the relative abundance of these proteoforms (paths). Our experimental results demonstrate the algorithm's capability to identify and quantify proteoform combinations encompassing a greater number of peaks. This advancement holds promise for enhancing the accuracy and comprehensiveness of proteoform quantification, addressing a crucial need in the field of top-down MS-based proteomics.Availability and implementation The software package are available at https://github.com/Zeirdo/TopMGQuant.
Keywords:
MASS
SOFTWARE

Journal

Bioinformatics cover
Bioinformatics
IF:
5.4
Papers:
1.1K
Citations:
17.9W

Organization

C
City Univ Hong Kong
Scholars:
2.1K
Papers: 1.4K
Citations: 810
Cited Papers

Cited Papers

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Multiplexed mass spectrometry of individual ions improves measurement of proteoforms and their complexes
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A mass graph-based approach for the identification of modified proteoforms using top-down tandem mass spectra
err2016-12-21
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errQiang Kou; Si Wu; Nikola Tolić; Ljiljana Paša-Tolić; Yunlong Liu; Xiaowen Liu
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Identification of Ultramodified Proteins Using Top-Down Tandem Mass Spectra
err2013-11-15
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errLiu, Xiaowen; Hengel, Shawna; Wu, Si; Tolic, Nikola; Pasa-Tolic, Ljiljana; Pevzner, Pavel A.
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Proteoform Suite: Software for Constructing, Quantifying, and Visualizing Proteoform Families
err2017-12-15
err43
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errCesnik, Anthony J.; Shortreed, Michael R.; Schaffer, Leah V.; Knoener, Rachel A.; Frey, Brian L.; Scalf, Mark; Solntsev, Stefan K.; Dai, Yunxiang; Gasch, Audrey P.; Smith, Lloyd M.
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Peptide Identification from Mixture Tandem Mass Spectra
err2010-07-01
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errOAAI
errWang, Jian; Perez-Santiago, Josue; Katz, Jonathan E.; Mallick, Parag; Bandeira, Nuno
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