April 2006 Kim Hammond-Kosack Wheat Pathogenesis Programme Jacob Koehler Bioinformatics and Biomaths...
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Transcript of April 2006 Kim Hammond-Kosack Wheat Pathogenesis Programme Jacob Koehler Bioinformatics and Biomaths...
April 2006
Kim Hammond-KosackWheat Pathogenesis Programme
Jacob Koehler Bioinformatics and Biomaths Division
PHI-base
PHI-base@Rothamsted
A database containing expertly curated molecularand biological information on genes proven toaffect the outcome of pathogen-host interactions
Winnenburg, Baldwin et al., (2006) Nucleic Acids Research 34: 459 – 465Balwin, Winnenburg et al., (2006) Mol. Plant Microbe Interact (accepted)
http://www.phi-base.org
An organism that, to complete a part or all of its life cycle, grows inside another organism and in so doing has a detrimental effect on its host.
Definition of a pathogen
Identification of pathogenicity, virulence and effector genes
Methods: Forward and Reverse Genetics Pathogen transformation involving protoplast or Agrobacterium mediated Gene disruption, replacement or silencing Purification of secreted proteins Map based cloning
Life cycle on host
completed
Pathogenicity factor
DISEASE=
Effector = activate / suppress plant disease resistance
Searching for Pathogenicity Genes
• Keyword search of the Web of Science and PubMed– (fung* or yeast) and (gene or factor) and
(pathogenicity or virulen* or avirulence gene*)
1277 1390 1413
PubMed
2677
Web of Science
2803
0
50
100
150
200
250
300
350
400
450
500
1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005
Year
Pa
pe
rs
0
25
50
75
100
125
150
175
200
225
250
Ge
ne
s
WOS
Pubmed
Cumulative Total of Plant Pathogen Genes
Cumulative Total of Animal Pathogen Genesf, g
ba
d,e
c
a Saccharomyces cerevisiae genome sequenced d Ashbya gossypii genome sequenced b First Magnaporthe grisea EST deposited in GenBank e First version of COGEME made available online c Candida albicans genome sequenced f Neurospora crassa genome sequenced
g Magnaporthe grisea genome sequenced
Pathogenicity gene publication rate is rising
Papers /year Cumulative
genes
Why PHI-base?
S. cerevisiae(sequenced genome)
Rice blast Comparative genomics Gene and protein function studies
Candida albicans Candida glabrata Fusarium ear blight
What is the cause of pathogenicity ?
Novel genes
Gene loss
Selective gene regulation
Saprophytes Pathogens
Plantpathogens
Animal pathogens
Immuno-compromisedhumans
Plant pathogens Human pathogens
To finish Healthy plants
http://www.phibase.org
PHI:125 – Candida albicans SAP4
PHI:44 Fusarium graminearum TRI5 gene codes for trichodiene synthase
Database Headings
Gene name Disease name Pathogen species Vegetative spores Experimental host Sexual spores Function In vitro growth Phenotype of mutant Spore germination Mating defect prior to penetration Essential gene (Lethal knockout) Pre-penetration defect Inducer Penetration defect Host response Post-penetration defect Experimental evidence PHI-base accession Entered by: EMBL accession Manual (M) or textmining (T) Linkout accession Literature ID Database Literature source Host NCBI Taxonomy ID Full citation Pathogen NCBI Taxonomy ID Author email Monocot/Dicot plant Comments Pathway
No effect
PHI-base@Rothamsted
405 entries for genes from plant, fungal and animal attacking fungi and Oomycetes
Version 2.1 (Jan 06)
Host Pathogen Species
Host Species
Pathogenicity Genes
Virulence Genes
Effector genes
Animal 10 5 40 129 0Plant 42 32 66 110 13Fungal 2 3 0 3 0
Version 2.2 (April 06) – 481 entries includes 40 where the gene deletion fails to affect the phenotype
The top 10 species in PHI-Base
Species Name Host Taxonomy Number of genes
Candida albicans Animal Ascomycota 102
Cryptococcus neoformans Animal Basidiomycota 50
Magnaporthe grisea Plant Ascomycota 44
Ustilago maydis Plant Basidiomycota 29
Aspergillus fumigatus Animal Ascomycota 13
Botrytis cinerea Plant Ascomycota 12
Fusarium graminearum Plant Ascomycota 12
Fusarium oxysporum Plant Ascomycota 12
Colletotrichum lagenarium Plant Ascomycota 10
peer-reviewed publications only
Where do you publish ?
52% of PHI-base entries were recovered from 5 journals
Molecular Plant-Microbe InteractionsMolecular MicrobiologyInfection and ImmunityThe Plant CellEukaryotic Cell
PUBMED covers 4,800 journals, WOS 8,700 journals
The remaining 48% of entries were obtained from an additional 45 journals
MIPS categories in PHI-base
No unknown function category !!!
Common gene functions required by fungi and Oomyceteswhich infect plant or animal hosts
Plant Pathogens*
* Number of distinct species
Animal Pathogens*
MAP kinase 12 2
G protein subunit 10 2
ABC transporter 5 1
Adenylate cyclase 4 2
Chitin Synthase 3 2
PKA catalytic subunit 3 2
Polyketide synthase 3 2
MAP kinase kinase kinase 3 2
MAP kinase kinase 3 1
Cyclophilin 2 1
Isocitrate lyase 2 1
Fatty acid synthetase 1 1
Methionine synthase 1 1
Trehalose-6-phosphate synthase 1 1
Superoxide dismutase 1 3
Adenylate forming enzymes 3 0
Tetraspanin 3 0
Endopolygalacturonase 3 0
Pectate lyase 2 0
PKA regulatory subunit 2 0
Specific gene functions required by either plant or animal infecting fungi and Oomycetes
“possibly just a snap shot in time”
Plant Pathogens*
Animal Pathogens*Plant specific
Animal specific
* Number of distinct species
Aspartyl proteinase 0 1
Phospholipase B 0 2
Candida albicans – Secreted Aspartyl Proteinases
Ortoneda et al. (2004) Infect. Immun. 72:1760-1766
2 x 107 conidia
The Fusarium oxysporum multihost model:isolate 4287 infects tomato plants and immunodepressed mice
20 mm 20 mm
Lung Heart
conidia
Time after infection (days)0 2 4 6 8 10 12 14
Su
rviv
al (
%)
0
20
40
60
80
100
wt wt heat-killed
Survival
Role of Fusarium oxysporum genes in virulence on plant and mammalian hosts
Biological functionGene Description
Signal transductionfmk1 MAP kinase
Signal transductionfgb1 G subunit
Ambient pH responsepacC Transcription factor
Unknownfpr1 PR-1 protein family
fmk1+fgb1
Yes
No
No
Yes
Yes
Requiredon plants
No
Yes
Yes
No
Yes
Requiredon mammals
Signal transduction
Antonio de Pietro’s group at the University of Cordoba, Spain Josep Guarro's group at the University Rovira y Virgili, Spain
Future versions of PHI-base
• Text-mining– Semi-automated literature searching and
database curation (pilot test – 70% recall, 40% precision)
• BLAST search facility– Sequence similarity comparisons with all the
pathogenicity genes
• Other pathogen-host data– Plant resistance and defence signalling genes– Fungicide targets– Other invader types e.g. bacteria, nematodes
Interactive pathway and network maps
Species experts
Plant Pathogenic fungi and Oomycetes
21 experts covering 17 species
Animal Pathogenic fungi
Plant resistance / defence genes
16 experts covering 15 interaction types
Plant bacterial effector genes3 experts
4 experts covering 3 species
Existing and future links
Pathogen Host Interactions database (PHI-base)
Contains expertly curated molecular and biological information on genes proven to affect the interaction outcome
405 gene entries – 169 animal, 176 plant, 3 fungi
54 pathogenic species, fungi and Oomyctes
~ 50% entries have functions in cellular communication/ signal transduction or metabolism
Comparative genomics
Medical and agricultural scientists, evolutionarybiologists and bioinformaticians
Thomas Baldwin*Martin UrbanKim Hammond-Kosack
Many thanks to
John AntoniwJohn KeonJohn LucasJason Rudd
Rainer WinnenburgJacob KoehlerChris Rawlings
*
Other beta testersDarren SoanesNick Talbot
Wheat Pathogenesis Bioinformatics and Text mining