Open Access Research

Microevolutionary analysis of Clostridium difficile genomes to investigate transmission

Xavier Didelot1*, David W Eyre23, Madeleine Cule1, Camilla LC Ip1, M Azim Ansari1, David Griffiths23, Alison Vaughan23, Lily O'Connor3, Tanya Golubchik1, Elizabeth M Batty1, Paolo Piazza4, Daniel J Wilson24, Rory Bowden134, Peter J Donnelly14, Kate E Dingle35, Mark Wilcox67, A Sarah Walker238, Derrick W Crook23, Tim E A Peto23 and Rosalind M Harding9*

Author Affiliations

1 Department of Statistics, University of Oxford, 1 South Parks Road, Oxford OX1 3TG, UK

2 Nuffield Department of Clinical Medicine, University of Oxford, John Radcliffe Hospital, Headley Way, Oxford, OX3 9DU, UK

3 Oxford Biomedical Research Centre, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UK

4 Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, UK

5 Nuffield Department of Clinical Laboratory Sciences, Headley Way, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DU, UK

6 Department of Microbiology, The General Infirmary, Old Medical School, Great George Street, Leeds LS1 3EX, UK

7 Leeds Institute of Molecular Medicine, University of Leeds, Beckett Street, Leeds LS9 7TF, UK

8 MRC Clinical Trials Unit, 125 Kingsway, London, WC2B 6NH, UK

9 Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, UK

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Genome Biology 2012, 13:R118  doi:10.1186/gb-2012-13-12-r118

Published: 21 December 2012

Additional files

Additional file 1:

Table summarizing the longitudinal data. Each row corresponds to one of the 91 patients for which two samples were taken on different dates, and the columns indicate when the two samples were taken and how they differed.

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Additional file 2:

Table summarizing the transmission data. Each row corresponds to one of the 486 CDI cases described in the main text.

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Additional file 3:

Figure showing the microevolutionary analysis for all 15 groups. Equivalent plot to Figure 1b for the 15 groups highlighted in Figure 1a.

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Additional file 4:

Table comparing the effect of considering pairs within one or three months of each other. Proportion of pairs of cases for which the TMRCA could be less than six months ago, when considering pairs of cases from the same ST and separated by a maximum of one month (left) or three months (right).

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Additional file 5:

Figure assessing the strength of agreement of the epidemiological and genomic analyses of transmission. The arrow at Kappa = 0.49 indicates Cohen's Kappa coefficient of agreement between links produced by the genomic (TMRCA <6 months) and epidemiological (shared time and space on hospital wards) analysis. The histogram shows the density of Kappa arising by chance, estimated using 10,000 random permutations of the epidemiological labels within each ST.

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Additional file 6:

Table summarizing the results of instantaneous within-host genomic diversity. Each row corresponds to one of seven experiments where 9 to 12 genomes were sequenced from multiple colonies grown from a single clinical sample. The genetic relationships between the genomes is described, and the average pairwise distance between genomes p is reported in the last column.

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