MLST_F

MLST_F is a software framework that analyzes the within-host diversity of bacterial pathogens using multi-locus sequence typing (MLST) data derived from whole-genome sequencing (WGS). The tool operates in two main stages:

1. Individual sample processing: MLST_F assigns a set of alleles and their proportions at each locus in the MLST scheme for each sample.

2. Strain type association: MLST_F associates each sample with a set of strain types using the alleles and proportions obtained in the first stage. It minimizes the number of previously unobserved strains across all samples while selecting unobserved strains as close as possible to the observed ones, respecting the allele proportions.

Both stages are solved using mixed integer linear programming (MILP). MLST_F has been shown to perform accurately on simulated data and has generated results suggesting high diversity in Borrelia burgdorferi, the causative agent of Lyme disease. The framework applies to any bacterial pathogen with an MLST scheme. It enables robust strain typing in the presence of within-host heterogeneity, addressing a challenge not currently met by existing pathogen genomics methodologies.