AA_stat

AA_stat analyzes shotgun proteomics open-search and ultra-tolerant tandem mass spectrometry results to identify and characterize unexpected amino acid modifications and post-translational modifications.

Key Features:

• Amino Acid Frequency Analysis: Analyzes frequencies of amino acids associated with observed mass shifts to generate hypotheses about in‑vitro and unannotated modifications.
• MS/MS-Based Localization and Scoring: Localizes mass shifts using MS/MS data, supports localization of mass shifts resulting from the sum of multiple modifications, and assigns scores to assess localization accuracy.
• Inference of Fixed Modifications: Infers fixed modifications to enhance sensitivity of subsequent searches.
• Error Detection and Correction: Infers monoisotopic peak assignment errors and proposes variable modifications based on the abundance patterns of specific mass shift localizations to improve closed-search yields.
• Mass Calibration Algorithm: Applies an algorithm to account for partial systematic shifts in mass measurements for more precise calibration and interpretation.
• Integration and Interpretation of Mass Shifts: Integrates analytical results and produces a ranked list of possible interpretations for observed mass shifts.

Scientific Applications:

• Profiling Amino Acid Modifications: Profiles both abundant and rare amino acid modifications to support discovery of novel PTMs.
• Interpretation of Open/Ultra-Tolerant Searches: Interprets results from open or ultra-tolerant database searches to refine identification and characterization of modifications.
• Improving Closed-Search Yield: Increases closed-search identification yield by correcting monoisotopic assignment errors and inferring fixed and variable modifications.
• Hypothesis Generation for In‑Vitro Modifications: Generates hypotheses regarding in‑vitro modifications not accounted for in standard databases.

Methodology:

Performs amino acid frequency analysis of mass shifts, MS/MS-based localization and scoring including summed modifications, inference of fixed and variable modifications and monoisotopic peak assignment errors from localization abundance, a mass calibration algorithm for partial systematic shifts, and ranking of candidate interpretations.