Inferences on Mycobacterium Leprae Host Immune Response Escape and Antibiotic Resistance Using Genomic Data and GenomeFastScreen

摘要

The identification in bacteria, of the set of genes and amino acid positions showing evidence for positive selection, can give insight, among others, on which genes and amino acid positions are responsible for modulating the host immune response. However, such analyses are time consuming, and the frequency of genes showing evidence for positively selected amino acid sites (PSS) can be low. Therefore, the quick identification of the set of genes that likely show PSS can lead to great savings in both computational and research time. Here, we present GenomeFastScreen, a Compi-based pipeline distributed as a Docker image, that automates the process of identifying genes that likely show PSS, starting from a set of FASTA files, one per genome, containing all coding sequences. GenomeFastScreen automatically removes problematic sequences such as those showing ambiguous positions and identifies orthologous gene sets. It is also possible to identify the orthologous genes in an external reference species, a requirement for comparisons across species, or to conduct gene ontology enrichment analyses when there is no data for the species being analysed. An example of what can be achieved when using the GenomeFastScreen pipeline is given for Mycobacterium leprae that causes leprosy. In this species, after detailed analyses, PSS were found at 31 genes, including nine genes likely relevant in the context of leprosy. The orthologs of those genes in M. tuberculosum (the species used as external reference) are Rv3632 (a protein membrane gene), Rv0177 (a mcel gene), PPE68 (a cell envelope protein), RpfB (a resuscitation-promoting factor), RecG (that provides protection against mitomycin C), lipQ and lipU (lipases) and Rv3220c and tesBl (esterases). Therefore, the study of these genes may reveal interesting hints on the modulation of the different M. leprae phenotypes.