#40 · Genomics

Site-level roll-up and cleavable cross-linkers sharpen structural proteomics readouts

The dominant thread is residue-resolved readout of modification and structural state in bottom-up and cross-linking proteomics. A benchmark of peptide-to-protein roll-up strategies for site-level PTM and LiP-MS quantification introduces a site-centric roll-up for proteolytic fragments, providing a direct comparison of how aggregation choices affect site-level results. In parallel, diazirine photo-cross-links are shown to be MS-cleavable, and a side-chain fingerprint machine-learning model with a rule-based filter improves XL-MS site identification and false discovery control. A separate preprint applies DNA-linked peptides on MinION nanopores, with feature-based and deep-learning classifiers, to identify peptides, an orthogonal non-mass-spectrometry route. The shared contribution across the mass spectrometry items is explicit handling of site identity during quantification and identification.