FLASHDeconv: Ultrafast, High-Quality Feature Deconvolution for Top-Down Proteomics

Kyowon Jeong; Jihyung Kim; Manasi Gaikwad; Siti Nurul Hidayah; Laura Heikaus; Hartmut Schlüter; Oliver Kohlbacher

doi:10.1016/j.cels.2020.01.003

FLASHDeconv: Ultrafast, High-Quality Feature Deconvolution for Top-Down Proteomics

Cell Syst. 2020 Feb 26;10(2):213-218.e6. doi: 10.1016/j.cels.2020.01.003. Epub 2020 Feb 19.

Authors

Kyowon Jeong¹, Jihyung Kim², Manasi Gaikwad³, Siti Nurul Hidayah³, Laura Heikaus³, Hartmut Schlüter³, Oliver Kohlbacher⁴

Affiliations

¹ Applied Bioinformatics, Department for Computer Science, University of Tübingen, Sand 14, 72076 Tübingen, Germany; Institute for Bioinformatics and Medical Informatics, University of Tübingen, Sand 14, 72076 Tübingen, Germany. Electronic address: jeong@informatik.uni-tuebingen.de.
² Applied Bioinformatics, Department for Computer Science, University of Tübingen, Sand 14, 72076 Tübingen, Germany; Institute for Bioinformatics and Medical Informatics, University of Tübingen, Sand 14, 72076 Tübingen, Germany.
³ Mass Spectrometric Proteomics, Institute of Clinical Chemistry and Laboratory Medicine, Campus Forschung, Universitätsklinikum Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany.
⁴ Applied Bioinformatics, Department for Computer Science, University of Tübingen, Sand 14, 72076 Tübingen, Germany; Institute for Bioinformatics and Medical Informatics, University of Tübingen, Sand 14, 72076 Tübingen, Germany; Center for Quantitative Biology, University of Tübingen, Sand 14, 72076 Tübingen, Germany; Biomolecular Interactions, Max Planck Institute for Developmental Biology, Max-Planck-Ring 4, 72076 Tübingen, Germany; Translational Bioinformatics, University Hospital Tübingen, Hoppe-Seyler-Str. 9, 72076 Tübingen, Germany.

PMID: 32078799
DOI: 10.1016/j.cels.2020.01.003

Abstract

Top-down mass spectrometry (TD-MS)-based proteomics analyzes intact proteoforms and thus preserves information about individual protein species. The MS signal of these high-mass analytes is complex and challenges the accurate determination of proteoform masses. Fast and accurate feature deconvolution (i.e., the determination of intact proteoform masses) is, therefore, an essential step for TD data analysis. Here, we present FLASHDeconv, an algorithm achieving higher deconvolution quality, with an execution speed two orders of magnitude faster than existing approaches. FLASHDeconv transforms peak positions (m/z) within spectra into log m/z space. This simple transformation turns the deconvolution problem into a search for constant patterns, thereby greatly accelerating the process. In both simple and complex samples, FLASHDeconv reports more genuine feature masses and substantially fewer artifacts than other existing methods. FLASHDeconv is freely available for download here: https://www.openms.org/flashdeconv/. A record of this paper's Transparent Peer Review process is included in the Supplemental Information.

Keywords: feature deconvolution; intact protein analysis; mass deconvolution; proteoform characterization; top-down proteomics.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Algorithms
Humans
Proteomics / methods*