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title Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Genomics of five Clostridium species Comparative Microbial.

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Presentation on theme: "title Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Genomics of five Clostridium species Comparative Microbial."— Presentation transcript:

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2 title Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Genomics of five Clostridium species Comparative Microbial Genomics Group A DNA-Centric View DIAGNOSIS, EPIDEMIOLOGY AND ANTIBIOTIC RESISTANCE OF THE GENUS CLOSTRIDIUM 17-18 October, 2003 - Parma, Italy Adv. Bioinformatics Lekture, 21 November, 2003

3 OVERVIEW 1. Comparison of five Clostridium genomes overview Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics Group Parma, 2003 2. Local View: DNA Structures and Clostridium Promoters 3. Global View: oligomer bias in Clostridium genomes

4 Cp 100 genomes Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics Group How do you compare more than 100 bacterial genomes? Parma, 2003

5 AT content Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics Group Parma, 2003

6 AT content Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics Group Parma, 2003

7 Global Repeats Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics Group Parma, 2003

8 Local Repeats Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics Group Parma, 2003

9 Purine stretches Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics Group Parma, 2003

10 Cp. rRNAs Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics Group Parma, 2003

11 Cp. protein Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics Group Parma, 2003

12 All paralogs Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics Group Parma, 2003

13 firmicutes Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics Group Parma, 2003

14 C.tetani plasmid Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics Group Parma, 2003

15 C.tet zoom Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics Group Parma, 2003

16 Promoter structures Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics Group Promoter Structural profile -10 “TATA box”-35 Parma, 2003

17 Campy pVir zoom Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics Group Parma, 2003

18 Promoter structure Comparative Microbial Genomics Group Center for Biological Sequence Analysis The Technical University of Denmark DTU -35 -10 TATA J. Mol. Biol., 326:1361-1372, (2003). Parma, 2003

19 Translation start aligned Comparative Microbial Genomics Group Center for Biological Sequence Analysis The Technical University of Denmark DTU J. Mol. Biol., 299:907-930, (2000). Parma, 2003

20 Promoter structures Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics Group Promoter Structural profile +1 CDS DNA curvature, flexibility important here melts rigid cruciform -10 -35 mRNA CDS  ’ -10 -35 +1   Parma, 2003

21 context Comparative Microbial Genomics Group Center for Biological Sequence Analysis The Technical University of Denmark DTU Information Depends on Context….. Parma, 2003

22 sigmas Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics Group Parma, 2003

23 Sigma70s with colour Comparative Microbial Genomics Group Center for Biological Sequence Analysis The Technical University of Denmark DTU Clostridium  ’s RpoH C. perfringens C. acetobutylicum C. tetani RpoD RpoS FliA SpoII spoI

24 Sig70 tree Center for Biological Sequence Analysis The Technical University of Denmark DTU Proteobacteria Firmicutes Actinobacteria  70 Chlamydia Cyanobact. “other phyla” RpoD RpoS “RpoD like” sigE sporulation iniation RpoH sigF sporulation sigG sporulation sigH RpoF flagella

25 sigmas Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics Group Parma, 2003

26 Environmental influence Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics Group  ’   -10 -35 DNA curvature, flexibility important here +1 50 mM salt 20  deg C  ’   -10-35+1 300 mM salt 37  deg C Parma, 2003

27 Context 2 Comparative Microbial Genomics Group Center for Biological Sequence Analysis The Technical University of Denmark DTU Information Depends on Context….. Parma, 2003

28 C. acetobutylicum Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics Group Parma, 2003

29 C. botulinum Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics Group Parma, 2003

30 C.difficile Atlas Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics Group Parma, 2003

31 C.tetani genome Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics Group Parma, 2003

32 Toxin tetanospasmin Anaerobic conditions allow germination of spores and production of toxins. The tetanus toxin is a 150 KDa protein, which is cleaved extra cellular, to a 100 Kda and a 50 Kda, that are binded with a sulfur bridge. Toxin binds in central nervous system Interferes with neurotransmitter release to block inhibitor impulses. Leads to unopposed muscle contraction and spasm.

33 C.perfringens Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics Group Parma, 2003

34 C.perf. skew Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics Group Parma, 2003

35 oligomers Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics Group LEADING STRAND, Oligomer bias (up to 8mers) Origin position: 0Strand difference(bits): 4105557 Oligo bits G 92292 GA 81583 AG 64095 AGA 60700 GG 46169 GAG 34200 GAA 33918 A 31417 GGA 31259 AA 25862 AGG 25340 AAG 24943 AGAG 24464 AGAA 23535 AAGA 23005 GAAA 18825 GAGA 18448 ATG 18129 GAT 17623 GGG 17200 LAGGING STRAND, Oligomer bias Terminus position: 1361000 Strand difference(bits): 3977053 Oligo bits C 93908 TC 82712 CT 62349 TCT 57477 CC 47113 TTC 35786 CTC 32995 TCC 32250 T 29779 CCT 24636 TT 23842 TTCT 23751 CTCT 22962 CTT 22661 TCTT 21517 TTTC 19334 CCC 18554 CAT 18537 TCTC 17833 ATC 17657

36 C. Perf skew2 Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics Group Parma, 2003

37 Organisms S/N Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics Group Parma, 2003

38 Signal/Noise plot Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics Group Parma, 2003

39 Summary 1. DNA sequence  DNA structure  Function summary Comparative Microbial Genomics Group Center for Biological Sequence Analysis The Technical University of Denmark DTU 2. Clostridium difficile is more likely to be variable. 3. Clostridium DNA is different! Parma, 2003

40 Acknowledgements Comparative Microbial Genomics Group Center for Biological Sequence Analysis The Technical University of Denmark DTU Acknowledgements Jakob Bondo Jimmy Hoffmann Hansen Paiman Khorsand-Jamal Anne Egholm Pedersen Maria Seier Petersen Peter Hallin Dave@cbs.dtu.dk The Danish Research Foundation www.cbs.dtu.dk Hans-Henrik Stærfeldt Lars Juhl Jensen Carsten Friis Marie Skovgaard Peder Worning Thomas Scheritz Pontén Søren Brunak Parma, 2003

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