Investigating host-pathogen interactions in tuberculosis using genomic data.


Tuberculosis caused by M.tuberculosis is an important global public health issue. Drug resistance is a serious challenge to effective control, and M. tuberculosis sequencing data can provide insights into resistance mutations (Coll et al, 2015), and classify strain-types (Coll et al, 2014) that have differential roles in pathogenesis and disease outcome. Host genetic studies using genome-wide genotyping chips are being applied to identify polymorphisms involved with disease susceptibility (Thye et al, 2010). Few studies have genomic data across host and pathogen, and using such data (Thailand, n=1500; Vietnam, n=2000) we will investigate genetic interactions between the organisms and disease outcome.


Thye T, Vannberg FO, …., African TB Genetics Consortium (TG Clark = member of the TB statistical analysis group); Wellcome Trust Case Control Consortium, Morris AP, Meyer CG, Horstmann RD, Hill AV. Genome-wide association analyses identifies a susceptibility locus for tuberculosis on chromosome 18q11.2. Nat Genet. 2010 Sep; 42(9):739-41.


Coll F, McNerney R, Guerra-Assunção JA, Glynn JR, Perdigão J, Viveiros M, Portugal I, Pain A, Martin N, Clark TG. A robust SNP barcode for typing Mycobacterium tuberculosis complex strains. Nature Comm. 2014 Sep 1;5:4812. doi: 10.1038/ncomms5812.


Coll F, McNerney R, Preston MD, Guerra-Assunção JA, …, Pain A, Clark TG. Rapid determination of anti-tuberculosis drug resistance from whole-genome sequences. Genome Medicine 2015 (in press).


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McEvoy, C. R. E., Cloete, R., Müller, B., Schürch, A. C., van Helden, P. D., Gagneux, S., … Gey van Pittius, N. C. (2012). Comparative analysis of Mycobacterium tuberculosis pe and ppe genes reveals high sequence variation and an apparent absence of selective constraints. PloS one, 7(4), e30593. doi:10.1371/journal.pone.0030593

Biological Areas:



Genes, development and STEM approaches to biology