Fit for Purpose Approach To Evaluate Detection of Amino Acid Substitutions in Shotgun Proteomics.

ABSTRACT: Amino acid substitutions (AASs) alter proteins from their genome-expected sequences. Accumulation of substitutions in proteins underlies numerous diseases and antibiotic mechanisms. Accurate global detection of AASs and their frequencies is crucial for understanding these mechanisms. Shotgun proteomics provides an untargeted method for measuring AASs but introduces biases when extrapolating from the genome to identify AASs. To characterize these biases, we created a "ground-truth" approach using the similarities betweenEscherichia coli and Salmonella typhimurium to model the complexity of AAS detection. Shotgun proteomics on mixed lysates generated libraries representing ∼100,000 peptide-spectra and 4161 peptide sequences with a single AAS and defined stoichiometry. Identifyi

SUBMITTER: Lundgren TJ 

PROVIDER: S-EPMC11003417 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature