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iHMMune-align Mutability ScoringThe mutability score refers to the potenital of a given nucleotide within an immunoglobulin heavy chain sequence to be targeted for mutation. The score accounts for differences in mutation potential of nucleotides resulting from the local sequence context. There are two means for calculating the mutability score; hotspot-based or trinucleotide-based.HotspotHotspot based scoring basis mutation potential of a target nucleotide on whether the nucleotide forms part of a hotspot motif. The hotspots which are considered are RGYW, WRCY and WAN (target nucleotide underlined). The mutability score given to each of these motifs was calculated from a set of mutations in non-productive sequences. The mutability score was based on the probability of mutation of a given hotspot motif and the frequency of the hotspot motif within the germline sequences.The mutability score for a G nucleotide that formed part of an RGYW motif was 3.412, WRCY motif was 3.456 and 1.903 for WAN. The mutability score for a non-hotspot target nucleotide, such as any T nucleotide or G/C/A that don't form part of a hotspot motif is 0.7143. TrinucleotideTrinucleotide scoring is based upon motifs of length 3 with the target nucleotide at the central position. All trinucleotides within the germline sequences were considered among a set of non-productive sequences. The scores were then calculated as described in (1). Briefly, the mutability score was calculated as the observed mutation frequency over the expected mutation frequency.References
1. A. M. Collins, Ikutani, M., Puiu, D., Buck, G. A., Nadkarni, A. and Gaeta, B.,
2004, Partitioning of Rearranged Ig Genes by Mutation Analysis Demonstrates D-D Fusion and V Gene Replacement in the Expressed Human Repertoire ,
Journal of Immunology, 172: 340-348
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