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The Hybrid Search: A Mass Spectral Library Search Method for Discovery of Modifications in Proteomics



Meghan C. Burke, Yuri A. Mirokhin, Dmitrii V. Tchekhovskoi, Sanford P. Markey, Stephen E. Stein, Jenny Heidbrink Thompson, Christopher Larkin


We present a mass spectral library based method to identify tandem mass spectra of peptides that contain unanticipated modifications and amino acid variants. We describe this as a ‘hybrid’ method since it combines matching both ion m/z and mass losses. The losses are differences in mass between an ion peak and its precursor mass. This difference, termed ΔMass, is used to shift the fragment ions in the library spectrum that contain the modification, thereby allowing library fragment ions that contain the unexpected modification to match the query spectrum. Clustered unidentified spectra from the Clinical Proteomic Tumor Analysis Consortium (CPTAC) and Chinese hamster ovary cells were used to evaluate this method. Results demonstrate the ability of the hybrid method to identify several varieties of unidentified spectra, including those due to an incomplete protein sequence database or to search settings that exclude the correct identification.
ACS Journal of Proteome Research
Created April 3, 2017, Updated February 13, 2020