msalign

msalign aligns LC-MS and LC-MS/MS datasets to integrate chromatographic features from enzymatic digests of protein mixtures for comprehensive proteomic analysis.

Key Features:

• Chromatographic Alignment: Aligns LC-MS and LC-MS/MS datasets based on chromatographic features to enable comparison and combination of data acquired from different instruments.
• Feature Extraction and Genetic Algorithm: Extracts peptides in the LC-MS dataset that match within a few ppm of their calculated theoretical masses from confident LC-MS/MS identifications and uses a genetic algorithm to fit a piecewise linear function to these matched peptides.
• Robust Fitness Function: Employs a fitness function that is insensitive to incorrect matches and flexible enough to accommodate discrete retention time shifts common between different LC instruments.

Scientific Applications:

• Hybrid Dataset Integration: Aligns ion trap LC-MS/MS data with accurate-mass LC-MS data from Fourier Transform Ion Cyclotron Resonance (FTICR) mass spectrometry to create hybrid datasets combining speed and high mass accuracy.
• Enhanced Peptide and Protein Identification: Improves peptide and protein identification by integrating LC-MS/MS identifications with high-accuracy LC-MS measurements.
• Quantitative Proteomics: When combined with FTICR data, supports increased precision and an extended linear dynamic range for quantitative proteomic analyses.

Methodology:

Searches the LC-MS dataset for peptides matching within a few ppm of theoretical masses from LC-MS/MS identifications, applies a genetic algorithm to fit a piecewise linear alignment function to matched peptides, and evaluates alignment with a fitness function tolerant of incorrect matches and discrete shifts.