Increased sensitivity with automated validation of XL-MS cleavable peptide crosslinks

A Keller, JD Chavez, JE Bruce - Bioinformatics, 2019 - academic.oup.com
A Keller, JD Chavez, JE Bruce
Bioinformatics, 2019academic.oup.com
Motivation Peptides crosslinked with cleavable chemical crosslinkers are identified with
mass spectrometry by independent database search of spectra associated with the two
linked peptides. A major challenge is to combine together the evidence of the two peptides
into an overall assessment of the two-peptide crosslink. Results Here, we describe software
that models crosslink specific information to automatically validate XL-MS cleavable peptide
crosslinks. Using a dataset of crosslinked protein mixtures, we demonstrate that it computes …
Motivation
Peptides crosslinked with cleavable chemical crosslinkers are identified with mass spectrometry by independent database search of spectra associated with the two linked peptides. A major challenge is to combine together the evidence of the two peptides into an overall assessment of the two-peptide crosslink.
Results
Here, we describe software that models crosslink specific information to automatically validate XL-MS cleavable peptide crosslinks. Using a dataset of crosslinked protein mixtures, we demonstrate that it computes accurate and highly discriminating probabilities, enabling as many as 75% more identifications than was previously possible using only search scores and a predictable false discovery rate.
Availability and implementation
XLinkProphet software is freely available on the web at http://brucelab.gs.washington.edu.
Supplementary information
Supplementary data are available at Bioinformatics online.
Oxford University Press