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Miracles can be achieved by mixture modelling of messy data. Chromopainter/FineSTRUCTURE/Globetrotter. Mixture modelling of an English palette. How does the information from metagenomics compare with what we would know if we had full genome sequences?. Not quite a metagenomics experiment. - PowerPoint PPT Presentation
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Miracles can be achieved by mixture modelling of messy data..
Chromopainter/FineSTRUCTURE/Globetrotter
How does the information from metagenomics compare with what we would know if we had full
genome sequences?
Qizhi Cao, Jianzhong Zhang, China CDC, Xavier Didelot, Imperial College
Not quite a metagenomics experiment
18 Helicobacter pylori sequenced from the same biopsy.
All of them were different.2 clades = 2 infections.
Reconstruction of recombination and mutation using ClonalFrame.
Years in past
Average import size 940bp
Ancestral sequences show interactions between strains in the pastAnd suggest longer mixed infection.
Classical metagenomic questionsHow many different infections?
What proportion of the population does each infectionaccount for?
Microevolutionary questionsWhat diversification has each infection undergone?
What is the functional effect of diversification?
Heroic questionsHow many infections were there in the past?
Ecological questions
Which strains thrive in the same environment?
Which strains thrive in the presence of each other?
Which strains competitively exclude one another?
What determines patterns of „succession“?
What determines infection rates by different strains?
Ecological genetic questions
How do strains adapt to new environments?
Epidemiology of infection amongst a free-range broiler breeder flock: two stages of infection
Colles et al. (2011) PLoS One 6(12):e22825
A rapid turnover of Campylobacter STs amongst individual birds
Chicken Week of the year8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 1 2 3 4 5 6
23456789
10
49 661 148751 814 176453 827 3120
443 828 Negative538 945573 958574 1089586 1090607 1257
Sequence types:
Colles et al, Unpublished
Clonal complexes isolated from a broiler breeder flock over time
9 19 26 30 9 16 23 1 8 15 22 29 5 26 4 10 17 24 1 7 14 21 28 5 13 19 27 2 9 16 23 31 6 13 20 27 4 11 18 25 1 8 15 22 29 6 13 20 4 10 17 31 8
Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec Jan Feb
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
ST-828 complexST-692 complexST-661 complexST-607 complexST-574 complexST-573 complexST-49 complexST-45 complexST-443 complexST-257 complexST-21 complexST-1287 complexST-1275 complexST-1150 complex
Colles et al, Unpublished
All the strains in CG1
The strains in CG1+S093
The strains in CG1+S093+CG2
The strains in CG1+S093+CG2+1 unrelated strain
SNP density in 1Kbp windows
Amongst 53 unrelated strains, strong non-random associationsbetween loci are almost entirely due to close genetic linkage
Host-restricted and multihost lineages of C. jejuni
952
22
42
45
177
682
48
1275
661692
61
206
354
257
1034
57421
Association study Method: Word analysis ST-45 complex
number word host1(total=14)host2(total=9)pvalue Info. Locus>388 GTTTAAAATTATTTAAATAGAAAGATATTT 4 9 1.50E- 06 Partial match found CAMP0030>49 CCATCGATTAAATATAACTTACTTTATCAT 5 9 4.30E- 05 Partial match found CAMP0043>6840 TAAAGCTTTAAAAAGTATTTTGTTTAAAAT 5 9 4.30E- 05 Partial match found CAMP0059>1130 GATTTATGATTTCAAAAAATTTTCAATAAA 2 6 4.30E- 05 Partial match found CAMP0092>1371 TATTTAAATAGAAAGATATTTTATGAAAAA 4 9 1.50E- 06 Partial match found CAMP0116
56
90
70
4
91
92
124
32
79
39
84
111
181
81
131
52
103
57
54
45
102
55
114
100
128
104
82
112
119
34
38
44
48
51
52
31
33
39
46
54
40
47
55
37
41
43
30
45
32
49
36
50
53
56
35
42
0.01
9034 host associated words in ST-45 complex
Map to 99 genes in total but 76% of words map to 10 contiguous genes (region 3)