Mottle

Mottle estimates substitution distances between highly divergent genomic sequences by constructing whole-genome maps with short-read mappers and isolating homologous fractions via gradient descent to support viral genomics and taxonomic classification.

Key Features:

• High-Divergence Accuracy: Maintains stability and accuracy across substitution rates from 0.66 to 0.96 substitutions per base pair.
• Utilization of Short-Read Mappers: Constructs whole-genome maps using short-read mappers to identify homologous regions in highly divergent sequences.
• Gradient Descent Methodology: Isolates homologous fractions of sequences through gradient descent to enable precise substitution distance calculations across evolutionary divergences.
• Application in Viral Genomics: Applicable to viral genomes due to high mutation rates, small genome sizes, and sparse taxonomy for analyzing evolutionary relationships between divergent viral sequences.
• Viral Discovery and Taxonomic Classification: Identifies viral outgroup genomes at the family-order level with reported 95% accuracy and provides a benchmark for homology search and taxonomic classification methods.

Scientific Applications:

• Evolutionary Studies: Provides substitution distance measures for investigating evolutionary relationships between highly divergent sequences.
• Viral Genomics Research: Supports analysis of viral genome evolution, high mutation-rate contexts, and novel virus discovery under sparse taxonomy.
• Benchmarking Homology Tools: Evaluates performance of homology search tools and taxonomic classification methods in scenarios involving highly divergent sequences.

Methodology:

Constructs whole-genome maps using short-read mappers and isolates homologous sequence fractions via gradient descent to compute substitution distances.