CIDer: A Statistical Framework for Interpreting Differences in CID and HCD Fragmentation.

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Journal of proteome research


genomics; washington; seattle; isb


Library searching is a powerful technique for detecting peptides using either data independent or data dependent acquisition. While both large-scale spectrum library curators and deep learning prediction approaches have focused on beam-type CID fragmentation (HCD), resonance CID fragmentation remains a popular technique. Here we demonstrate an approach to model the differences between HCD and CID spectra, and present a software tool, CIDer, for converting libraries between the two fragmentation methods. We demonstrate that just using a combination of simple linear models and basic principles of peptide fragmentation, we can explain up to 43% of the variation between ions fragmented by HCD and CID across an array of collision energy settings. We further show that in some circumstances, searching converted CID libraries can detect more peptides than searching existing CID libraries or libraries of machine learning predictions from FASTA databases. These results suggest that leveraging information in existing libraries by converting between HCD and CID libraries may be an effective interim solution while large-scale CID libraries are being developed.


Institute for Systems Biology