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

BACKGROUND: 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. RESULTS: We 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. CONCLUSIONS: Experiments 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12859-018-2273-4) contains supplementary material, which is available to authorized users.