A graph-based approach for proteoform identification and quantification using top-down homogeneous multiplexed tandem mass spectra

Kaiyuan Zhu,Xiaowen Liu

doi:10.1186/s12859-018-2273-4

Abstract

BackgroundTop-down homogeneous multiplexed tandem mass (HomMTM) spectra are generated from modified proteoforms of the same protein with different post-translational modification patterns. They are frequently observed in the analysis of ultramodified proteins, some proteoforms of which have similar molecular weights and cannot be well separated by liquid chromatography in mass spectrometry analysis.ResultsWe formulate the top-down HomMTM spectral identification problem as the minimum error k-splittable flow problem on graphs and propose a graph-based algorithm for the identification and quantification of proteoforms using top-down HomMTM spectra.ConclusionsExperiments on a top-down mass spectrometry data set of the histone H4 protein showed that the proposed method identified many proteoform pairs that better explain the query spectra than single proteoforms.

Highlights

Top-down homogeneous multiplexed tandem mass (HomMTM) spectra are generated from modified proteoforms of the same protein with different post-translational modification patterns
The minimum error k-splittable flow (MEkSF) problem is Non-deterministic polynomial-time hard (NP-hard) on directed acyclic graphs when k is part of the input, which can be proved by reducing from the partition problem [23]. (See Additional file 1.) Here we propose a dynamic programming algorithm for the MEkSF problem for k=2 on layered directed graphs
We implemented the dynamic programming algorithm for the Minimum error 2-splittable flow (ME2SF) problem in C++ and tested it on a topdown mass spectrometry (MS)/MS data set of the human histone H4 protein

Summary

Introduction

Top-down homogeneous multiplexed tandem mass (HomMTM) spectra are generated from modified proteoforms of the same protein with different post-translational modification patterns. They are frequently observed in the analysis of ultramodified proteins, some proteoforms of which have similar molecular weights and cannot be well separated by liquid chromatography in mass spectrometry analysis. A ultramodified protein may have many similar proteoforms with similar weights and different post-translational modification (PTM) patterns. These proteoforms are often not well separated in top-down MS analysis [1]. In data-independent acquisition MS, which has been rapidly developed in the past several years, the precursor ions in a large mass-to-charge ratio (m/z value) interval are collected for MS/MS analysis, resulting

Results

Discussion

Conclusion