Whole genome sequencing for M/XDR tuberculosis surveillance and for resistance testing  T.M. Walker, M. Merker, T.A. Kohl, D.W. Crook, S. Niemann, T.E.A. Peto  Clinical Microbiology and Infection  Volume 23, Issue 3, Pages 161-166 (March 2017) DOI: 10.1016/j.cmi.2016.10.014 Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases Terms and Conditions

Fig. 1 Factors influencing molecular clock and genetic diversity in multidrug/extensively drug-resistant (M/XDR) tuberculosis. (a, b) Population-based effects. (a) Phylogenetic tree of the Mycobacterium tuberculosis complex lineages with the ‘Beijing’ lineage, purported to have a higher mutation rate, coloured red. (b) Cartoon showing the emergence of the same example mutation independently on different branches of the tree (‘homoplasy’) due to positive selection. (c, d) Evolution within the individual. (c) Cartoon of the circular M. tuberculosis complex genome/ chromosome in which a single drug resistance mutation (in red) arises and is accompanied by compensatory or hitchhiking mutations (in blue), accelerating the rate of microevolution. (d) Cartoon of the evolution of M. tuberculosis complex strains within two hosts, (i) and (ii), infected by the same source at the same time point, 0. As patient (i) is not diagnosed until time point t, there has been opportunity for greater within-host evolution, and for the spontaneous emergence of M/XDR conferring mutations. Conclusions about the relatedness to case (ii) will be influenced by which strain is sampled from (i), and when. Clinical Microbiology and Infection 2017 23, 161-166DOI: (10.1016/j.cmi.2016.10.014) Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases Terms and Conditions

Fig. 2 Comparison of currently available diagnostic modalities to nanotechology-based whole-genome sequencing. Clinical Microbiology and Infection 2017 23, 161-166DOI: (10.1016/j.cmi.2016.10.014) Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases Terms and Conditions

Fig. 3 Advantages and remaining challenges of whole genome sequencing for surveillance and susceptibility testing. Clinical Microbiology and Infection 2017 23, 161-166DOI: (10.1016/j.cmi.2016.10.014) Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases Terms and Conditions