DeepMutationalScanningEngine: Fitness Landscape Mapping, Epistasis Detection, and Evolutionary Constraint Analysis
Introduction
Deep mutational scanning (DMS) uses high-throughput sequencing to measure fitness effects of all possible single amino acid substitutions. The resulting fitness landscape reveals which positions are functionally constrained and how mutations interact epistatically.
Methods
Fitness Scoring
Fitness = log2(frequency_selected / frequency_input). Synonymous variants used for normalization.
Epistasis
Epistasis = fitness_AB - (fitness_A + fitness_B). Positive = synergistic, negative = antagonistic.
Functional Sites
Positions where >50% of substitutions have fitness < −1.
Results
Beneficial=20.9%, neutral=45.6%, deleterious=33.5%. Functional sites=17. Epistasis r=0.933. Conservation-fitness r=−0.439.
Code Availability
https://github.com/BioTender-max/DeepMutationalScanningEngine
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