Proteoform Thursday: Nic Bollis presents “Mining Chimeric Mass Spectra for Co-eluting Peptides and Proteoforms”
Thursday, August 20, 2026 11:00 AM in Eastern Time (US and Canada)
Chimeric fragmentation spectra are pervasive in both bottom-up and top-down proteomics, yet standard search pipelines often 
assume one precursor per spectrum and thus discard a wealth of co-fragmented species. We developed a precursor-centric chimera search strategy in the open-source proteomics search engine MetaMorpheus that deconvolves all precursor ions within each precursor scan’s isolation window and searches each independently against the full fragment spectrum, preserving complete fragment ion information for every hypothesis. The method yielded 49% more peptide spectrum matches, 16% more unique peptides, and 4% more protein groups in bottom-up data, while top-down proteoform spectrum matches rose by 180%, proteoforms by 70%, and proteoform families by 9%.