MAPP

MAPP predicts the impact of amino acid substitutions on protein function by analyzing physicochemical variation within columns of protein sequence alignments using evolutionary data from diverse orthologs.

Key Features:

• Comparative Sequence Analysis: Uses comparative sequence analysis to predict the degree of functional impairment from missense mutations and reports a continuous spectrum of effects rather than a binary classification.
• Physicochemical Characterization: Quantifies physicochemical characteristics at each alignment position and evaluates how amino acid substitutions violate observed physicochemical constraints.
• Ortholog Diversity Improves Accuracy: Prediction accuracy increases with the inclusion of diverse orthologs because broader evolutionary variation reveals physicochemical constraints more comprehensively.
• Disease Correlation: Correlates the degree of physicochemical constraint violation caused by causative amino acid variants with grades of disease or cancer likelihood.

Scientific Applications:

• Protein Function Prediction: Predicts changes in protein function resulting from amino acid substitutions.
• Disease Correlation Studies: Links specific missense variants to disease severity or cancer risk by mapping constraint violations to clinical grades.
• Evolutionary Biology Research: Analyzes sequence variation across diverse orthologs to infer evolutionary pressures and constraints on protein function.

Methodology:

Analyzes physicochemical variation within alignment columns, quantifies physicochemical characteristics at each alignment position, leverages evolutionary data from diverse orthologs, and correlates observed constraint violations with functional impairment and disease grades.