Retention Time and Fragmentation Predictors Increase Confidence in Identification of Common Variant Peptides

Precision medicine focuses on adapting care to the individual profile of patients, for example, accounting for their unique genetic makeup. Being able to account for the effect of genetic variation on the proteome holds great promise toward this goal. However, identifying the protein products of genetic variation using mass spectrometry has proven very challenging. Here we show that the identification of variant peptides can be improved by the integration of retention time and fragmentation predictors into a unified proteogenomic pipeline. By combining these intrinsic peptide characteristics using the search-engine post-processor Percolator, we demonstrate improved discrimination power between correct and incorrect peptide-spectrum matches. Our results demonstrate that the drop in performance that is induced when expanding a protein sequence database can be compensated, hence enabling efficient identification of genetic variation products in proteomics data. We anticipate that this enhancement of proteogenomic pipelines can provide a more refined picture of the unique proteome of patients and thereby contribute to improving patient care.publishedVersio

Supplementary Data: Identifying Protein Haplotypes by Mass Spectrometry

Supplementary data related to the paper "Identifying Protein Haplotypes by Mass Spectrometry" SD1: FASTA file including all target protein sequences (Ensembl reference proteome, protein haplotype sequences, contaminant sequences), excluding decoys SD2: FASTA file including all target and decoy sequences SD3: List of all peptide-spectrum matches (PSMs) with all related metadata and quality control measures SD4: List of substitutions identified, along with IDs of corresponding PSMs To reproduce the post-processing steps, you can use the pipeline published at https://github.com/ProGenNo/IdentifyingHaplotypesByMS The repository also contains additional explanations of supplementary files contents.</p

Poster: Haplotypes and Human Diversity in Proteomics

Poster presented at the EuBIC-MS Winter School 2024ProHap is a python-based tool built to efficiently generate protein haplotype databases from phased genotypes of reference population panels.Full paper (preprint): https://doi.org/10.1101/2023.12.24.572591</p