host-pathogens interactions

Comparative genomics in the context of
host-pathogens interactions
Jérôme Gouzy, Yoann Beausse, Romain Fremez, François Enault, Thomas
Faraut
Thomas.Faraut@toulouse.inra.fr
INRA - Toulouse
EADGENE Days, 29-30 June 2006, Oslo, Norway.
Thomas Faraut and Christophe Klopp (INRA, France).
Copyright INRA 2006. Reproduced here with permission.
Comparative genomics in the context of host-pathogens interactions – p.1

Plan
Motivation
Methodological issues
Presentation of the tools : Narcisse, Alvira
Perspectives
EADGENE Days, 29-30 June 2006, Oslo, Norway.
Thomas Faraut and Christophe Klopp (INRA, France).
Copyright INRA 2006. Reproduced here with permission.
Comparative genomics in the context of host-pathogens interactions – p.2

Motivation
Comparative genomics in this complete genome sequence
aera.
How can we compare complete genome sequences ?
In what format do we expect the results of the comparison
of complete genomes ?
EADGENE Days, 29-30 June 2006, Oslo, Norway.
Thomas Faraut and Christophe Klopp (INRA, France).
Copyright INRA 2006. Reproduced here with permission.
Comparative genomics in the context of host-pathogens interactions – p.3

Socio-economic context
A small bioinformatic team (1 person) with an experience in
EST annotation (Iccare : Interspecific Comparative Clustering
and Annotation foR EST)
http://bioinfo.genopole-toulouse.prd.fr/iccare/
Support from eadgene was greatly appreciated:
6 months of bioinformatician engineer
12 months of post-doc
EADGENE Days, 29-30 June 2006, Oslo, Norway.
Thomas Faraut and Christophe Klopp (INRA, France).
Copyright INRA 2006. Reproduced here with permission.
Comparative genomics in the context of host-pathogens interactions – p.4

Scientific context
Before the beginning of the eadgene project...
Concerns in the methodological issues of comparing animal
complete genome sequences
with the encouragements and incentives of the REX eadgene
we began to work on
Comparing microbial pathogenetic genomes
Comparing viral strains
EADGENE Days, 29-30 June 2006, Oslo, Norway.
Thomas Faraut and Christophe Klopp (INRA, France).
Copyright INRA 2006. Reproduced here with permission.
Comparative genomics in the context of host-pathogens interactions – p.5

Scientific Issue
Back to the scientific problem :
How can we compare complete genomes ?
EADGENE Days, 29-30 June 2006, Oslo, Norway.
Thomas Faraut and Christophe Klopp (INRA, France).
Copyright INRA 2006. Reproduced here with permission.
Comparative genomics in the context of host-pathogens interactions – p.6

Dotplot Human × chicken
Genomes are compared at the nucleotide level.
EADGENE Days, 29-30 June 2006, Oslo, Norway.
Thomas Faraut and Christophe Klopp (INRA, France).
Copyright INRA 2006. Reproduced here with permission.
Comparative genomics in the context of host-pathogens interactions – p.7

Chaining elements
Local similarities are computed and chained according to the
longest increasing subsequence algorithm.
EADGENE Days, 29-30 June 2006, Oslo, Norway.
Thomas Faraut and Christophe Klopp (INRA, France).
Copyright INRA 2006. Reproduced here with permission.
Comparative genomics in the context of host-pathogens interactions – p.8

Chaining chains
EADGENE Days, 29-30 June 2006, Oslo, Norway.
Thomas Faraut and Christophe Klopp (INRA, France).
Copyright INRA 2006. Reproduced here with permission.
Comparative genomics in the context of host-pathogens interactions – p.9

Chaining chains
For animal genomes we have selected, somehow
arbitrarily, 5 different levels;
Only 3 different levels are considered for bacterial
genomes.
EADGENE Days, 29-30 June 2006, Oslo, Norway.
Thomas Faraut and Christophe Klopp (INRA, France).
Copyright INRA 2006. Reproduced here with permission.
Comparative genomics in the context of host-pathogens interactions – p.10

Comparing genomes
EADGENE Days, 29-30 June 2006, Oslo, Norway.
Thomas Faraut and Christophe Klopp (INRA, France).
Copyright INRA 2006. Reproduced here with permission.
Comparative genomics in the context of host-pathogens interactions – p.11

Comparing genomes
EADGENE Days, 29-30 June 2006, Oslo, Norway.
Thomas Faraut and Christophe Klopp (INRA, France).
Copyright INRA 2006. Reproduced here with permission.
Comparative genomics in the context of host-pathogens interactions – p.12

Comparing genomes
EADGENE Days, 29-30 June 2006, Oslo, Norway.
Thomas Faraut and Christophe Klopp (INRA, France).
Copyright INRA 2006. Reproduced here with permission.
Comparative genomics in the context of host-pathogens interactions – p.13

Comparing genomes
EADGENE Days, 29-30 June 2006, Oslo, Norway.
Thomas Faraut and Christophe Klopp (INRA, France).
Copyright INRA 2006. Reproduced here with permission.
Comparative genomics in the context of host-pathogens interactions – p.14

Narcisse
EADGENE Days, 29-30 June 2006, Oslo, Norway.
Thomas Faraut and Christophe Klopp (INRA, France).
Copyright INRA 2006. Reproduced here with permission.
Comparative genomics in the context of host-pathogens interactions – p.15

Narcisse
EADGENE Days, 29-30 June 2006, Oslo, Norway.
Thomas Faraut and Christophe Klopp (INRA, France).
Copyright INRA 2006. Reproduced here with permission.
Comparative genomics in the context of host-pathogens interactions – p.16

Narcisse
EADGENE Days, 29-30 June 2006, Oslo, Norway.
Thomas Faraut and Christophe Klopp (INRA, France).
Copyright INRA 2006. Reproduced here with permission.
Comparative genomics in the context of host-pathogens interactions – p.17

Narcisse
EADGENE Days, 29-30 June 2006, Oslo, Norway.
Thomas Faraut and Christophe Klopp (INRA, France).
Copyright INRA 2006. Reproduced here with permission.
Comparative genomics in the context of host-pathogens interactions – p.18

Narcisse
EADGENE Days, 29-30 June 2006, Oslo, Norway.
Thomas Faraut and Christophe Klopp (INRA, France).
Copyright INRA 2006. Reproduced here with permission.
Comparative genomics in the context of host-pathogens interactions – p.19

Narcisse
EADGENE Days, 29-30 June 2006, Oslo, Norway.
Thomas Faraut and Christophe Klopp (INRA, France).
Copyright INRA 2006. Reproduced here with permission.
Comparative genomics in the context of host-pathogens interactions – p.20

Narcisse
EADGENE Days, 29-30 June 2006, Oslo, Norway.
Thomas Faraut and Christophe Klopp (INRA, France).
Copyright INRA 2006. Reproduced here with permission.
Comparative genomics in the context of host-pathogens interactions – p.21

Narcisse
EADGENE Days, 29-30 June 2006, Oslo, Norway.
Thomas Faraut and Christophe Klopp (INRA, France).
Copyright INRA 2006. Reproduced here with permission.
Comparative genomics in the context of host-pathogens interactions – p.22

Narcisse animals
Available genomes :
human, mouse, rat, chicken, dog, cattle
http://bioinfo.genopole-toulouse.prd.fr/narcisse/
EADGENE Days, 29-30 June 2006, Oslo, Norway.
Thomas Faraut and Christophe Klopp (INRA, France).
Copyright INRA 2006. Reproduced here with permission.
Comparative genomics in the context of host-pathogens interactions – p.23

Narcisse bacterial
EADGENE Days, 29-30 June 2006, Oslo, Norway.
Thomas Faraut and Christophe Klopp (INRA, France).
Copyright INRA 2006. Reproduced here with permission.
Comparative genomics in the context of host-pathogens interactions – p.24

Narcisse bacterial
EADGENE Days, 29-30 June 2006, Oslo, Norway.
Thomas Faraut and Christophe Klopp (INRA, France).
Copyright INRA 2006. Reproduced here with permission.
Comparative genomics in the context of host-pathogens interactions – p.25

Viral comparative genomics
Virology entered as well the genomic aera :
Multiple viral strains from a single virus are being
sequenced
Analyzing viral genomes multiple alignments is a key step
for the understanding of viral genome dynamics
We propose in the Alvira tool an integrated approach for
multiple alignment analysis.
EADGENE Days, 29-30 June 2006, Oslo, Norway.
Thomas Faraut and Christophe Klopp (INRA, France).
Copyright INRA 2006. Reproduced here with permission.
Comparative genomics in the context of host-pathogens interactions – p.26

Alvira
Multiple alignment is viewed as a graph.
EADGENE Days, 29-30 June 2006, Oslo, Norway.
Thomas Faraut and Christophe Klopp (INRA, France).
Copyright INRA 2006. Reproduced here with permission.
Comparative genomics in the context of host-pathogens interactions – p.27

Alvira
Departure from the consensus can be identified at once
EADGENE Days, 29-30 June 2006, Oslo, Norway.
Thomas Faraut and Christophe Klopp (INRA, France).
Copyright INRA 2006. Reproduced here with permission.
Comparative genomics in the context of host-pathogens interactions – p.28

Alvira
Strain specific variation can be identified
EADGENE Days, 29-30 June 2006, Oslo, Norway.
Thomas Faraut and Christophe Klopp (INRA, France).
Copyright INRA 2006. Reproduced here with permission.
Comparative genomics in the context of host-pathogens interactions – p.29

Perspectives
A multiple alignement viewer for targeted regions of
animal genomes;
Develop, in collaboration with the Sigenae team, web
services to query the narcisse database.
EADGENE Days, 29-30 June 2006, Oslo, Norway.
Thomas Faraut and Christophe Klopp (INRA, France).
Copyright INRA 2006. Reproduced here with permission.
Comparative genomics in the context of host-pathogens interactions – p.30

Aknowledgements
Thanks a lot to Christophe Klopp.
EADGENE Days, 29-30 June 2006, Oslo, Norway.
Thomas Faraut and Christophe Klopp (INRA, France).
Copyright INRA 2006. Reproduced here with permission.
Comparative genomics in the context of host-pathogens interactions – p.31