PeCorA

PeCorA detects discordant peptide quantities in shotgun proteomics datasets to identify peptides whose quantitative behavior deviates from other peptides of the same protein, informing protein quantification and post-translational modification inference.

Key Features:

• Detection of Discordant Peptides: Identifies quantitative disagreements between peptides mapped to a single protein that may reflect heterogeneous proteoforms or technical artifacts.
• Linear Model Fitting: Employs linear models to evaluate whether a peptide's change in quantity across treatment groups deviates from other peptides assigned to the same protein.
• Post-Translational Modification (PTM) Detection: Facilitates direct and indirect detection of regulated PTMs by highlighting peptide-level quantitative deviations consistent with modification events.
• Identification of Poorly Quantified Peptides: Highlights poorly quantified peptides to refine data quality and reduce false positives when summarizing protein quantities.
• Application to Real-World Data: Revealed that approximately 15% of proteins in a mouse microglia stress dataset contain at least one discordant peptide.
• Case Study on COVID-19: Indicated an increased abundance of the inactive isoform of prothrombin in plasma from COVID-19 patients compared to non-COVID-19 controls.
• Implementation: Provided as an R package for analysis of peptide quantification data.

Scientific Applications:

• Proteomics Research: Enhances accuracy and interpretation of protein quantification in shotgun proteomic datasets by resolving peptide-level inconsistencies.
• PTM Studies: Assists in identifying and characterizing regulated post-translational modifications through peptide-level deviation analysis.
• Clinical Research: Enables peptide-resolved investigations of disease-associated proteoform changes, as demonstrated in COVID-19 plasma analyses.

Methodology:

PeCorA fits linear models to peptide quantification data to assess whether individual peptides' quantitative changes across treatment groups are consistent with other peptides from the same protein.