Responsable de l'équipe d'accueil

Rastogi
Nalin
nrastogi@pasteur-guadeloupe
0590897661

Personne encadrant le stage

Reynaud
Yann
0590897664

Lieu du stage

Institut Pasteur de la Guadeloupe, Les Abymes

Sujet du stage

Evolutionary history of Mycobacterium tuberculosis Lineages L1 and L3 at the worldwide scale using Whole Genome Sequencing (WGS) data
Context
Mycobacterium tuberculosis (MTB) genetic structuration, dispersal and evolution have been explored for years by genotyping allowing definition of 7 major lineages. If Lineages 2 and 4 for example have been studied in details using WGS, Lineage 1 (also called Indo-Oceanic or EAI) and Lineage 3 (East-African-Indian or CAS) were only studied using more “classical” approaches like spoligotyping, LSP and MIRU-VNTR, but reconstruction of evolutionary histories of these two lineages could be greatly improved thanks to WGS. The main objectives of this project are: (i) to explore in details genetic structuration and phylogeography of L1 and L3 at the worldwide scale, and (ii) to reconstruct evolutionary histories of these lineages.

M&M
Thousands of MTB genomes were sequenced last years and are available on open source databases (ENA, Genbank, Patric). As part of this research project, WGS of L1 and L3 isolates will be downloaded from main databases. We expect few hundreds to be downloaded. Isolates will be classified into sublineages using kvarq algorithm following Coll et al. rules (2014). Reads will be assembled, annotated and a core genome MLST (Multi Locus Sequence Typing) we be performed using Roary software to extract relevant SNPs. In parallel, SNPs calling could also be performed on complete reads using GATK and/or Samtools. Phylogenetic analyses will be run on RAXML and evolutionary histories over time reconstruct by Bayesian Skyline Plots using BEAST software.
MIRU-VNTR data of an enlarged dataset from the SITVIT2 database could also be used to perform Minimum Spanning Tree analyses, Bayesian Structure analyses and to compare allelic richness values of sublineages and between countries.

Skills of the student
Considering that this master training will be focused on bioinformatics analyses, students will be selected based on their personal motivation and interest in bioinformatics. Experience in Linux command lines, understanding of bacterial evolution, and good knowledge of English will be added assets for selection.

Please send motivation letter and CV to:
Dr. Yann Reynaud, Tuberculosis & Mycobacteria Unit, INSTITUT PASTEUR de la GUADELOUPE
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