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PHI-base
Kim Hammond-Kosack
Wheat Pathogenesis Programme
Jacob Koehler
Bioinformatics and Biomaths Division
April 2006
PHI-base@Rothamsted
A database containing expertly curated molecular
and biological information on genes proven to
affect the outcome of pathogen-host interactions
http://www.phi-base.org
Winnenburg, Baldwin et al., (2006) Nucleic Acids Research 34: 459 – 465
Balwin, Winnenburg et al., (2006) Mol. Plant Microbe Interact (accepted)
Definition of a pathogen
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.
Identification of pathogenicity, virulence and
effector genes
Pathogenicity
factor
Life cycle
on host
completed
= DISEASE
Effector
Methods:
= activate /
suppress
plant disease
resistance
Forward and Reverse Genetics
Pathogen transformation involving
protoplast or Agrobacterium mediated
Gene disruption, replacement or silencing
Purification of secreted proteins
Map based cloning
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*)
PubMed
Web of Science
2677
2803
1277
1390
1413
Pathogenicity gene publication rate is rising
500
250
WOS
450
400
Pubmed
Cumulative Total of Plant Pathogen Genes
225
f, g
Cumulative Total of Animal Pathogen Genes
200
d,e
350
300
150
Cumulative
125
genes
Genes
Papers
Papers /
year
175
c
250
200
a
100
b
150
75
100
50
50
25
0
0
1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005
Year
a Saccharomyces cerevisiae genome sequenced
b First Magnaporthe grisea EST deposited in GenBank
c Candida albicans genome sequenced
d Ashbya gossypii genome sequenced
e First version of COGEME made available online
f Neurospora crassa genome sequenced
g Magnaporthe grisea genome sequenced
Why PHI-base?
Rice blast
 Comparative genomics
 Gene and protein
function studies
S. cerevisiae
(sequenced genome)
Candida albicans
Candida glabrata
Fusarium ear blight
What is the cause of pathogenicity ?
Saprophytes
Pathogens
Novel genes
Gene loss
Selective gene regulation
Plant
pathogens
Animal
pathogens
Plant pathogens
Human pathogens
Healthy plants
To finish
Immuno-compromised
humans
http://www.phibase.org
PHI:125 – Candida albicans SAP4
PHI:44 Fusarium graminearum TRI5 gene codes for trichodiene synthase
Database Headings
Gene name
Pathogen species
Experimental host
Function
Phenotype of mutant
Mating defect prior to penetration
Pre-penetration defect
Penetration defect
Post-penetration defect
PHI-base accession
EMBL accession
Linkout accession
Database
Host NCBI Taxonomy ID
Pathogen NCBI Taxonomy ID
Monocot/Dicot plant
Pathway
Disease name
Vegetative spores
Sexual spores
In vitro growth
Spore germination
Essential gene (Lethal knockout)
Inducer
Host response
Experimental evidence
Entered by:
Manual (M) or textmining (T)
Literature ID
Literature source
Full citation
Author email
Comments
No effect
PHI-base@Rothamsted
Version 2.1 (Jan 06)
405 entries for genes from plant, fungal and animal
attacking fungi and Oomycetes
Host
Pathogen
Species
Host
Species
Pathogenicity
Genes
Virulence
Genes
Effector
genes
Animal
Plant
Fungal
10
42
2
5
32
3
40
66
0
129
110
3
0
13
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
Host
Taxonomy
Candida albicans
Animal
Ascomycota
102
Cryptococcus neoformans
Animal
Basidiomycota
50
Magnaporthe grisea
Plant
Ascomycota
44
Ustilago maydis
Plant
Basidiomycota
29
Species Name
Aspergillus fumigatus
Animal
Botrytis cinerea
Plant
Fusarium graminearum
Plant
Fusarium oxysporum
Plant
Colletotrichum lagenarium
Plant
Ascomycota
Ascomycota
Ascomycota
Ascomycota
Ascomycota
Number of genes
13
12
12
12
10
peer-reviewed publications only
Where do you publish ?
PUBMED covers 4,800 journals, WOS 8,700 journals
52% of PHI-base entries were recovered from 5 journals
Molecular Plant-Microbe Interactions
Molecular Microbiology
Infection and Immunity
The Plant Cell
Eukaryotic Cell
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 Oomycetes
which infect plant or animal hosts
Plant
Pathogens*
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
* Number of distinct species
Specific gene functions required by either plant
or animal infecting fungi and Oomycetes
“possibly just a snap shot in time”
Plant
Pathogens*
Animal
Pathogens*
Adenylate forming enzymes
3
0
Tetraspanin
3
0
Endopolygalacturonase
3
0
Pectate lyase
2
0
PKA regulatory subunit
2
0
Plant specific
Animal specific
Aspartyl proteinase
0
1
Phospholipase B
0
2
* Number of distinct species
Candida albicans – Secreted Aspartyl Proteinases
The Fusarium oxysporum multihost model:
isolate 4287 infects tomato plants and immunodepressed mice
2 x 107 conidia
Survival
Survival (%)
100
80
wt conidia
wt heat-killed
60
40
20
0
0
2
4
6
8 10 12 14
Time after infection (days)
20 mm
20 mm
Lung
Heart
Ortoneda et al. (2004) Infect. Immun. 72:1760-1766
Role of Fusarium oxysporum genes in virulence
on plant and mammalian hosts
Required
on plants
Required
on mammals
Gene
Description
Biological function
fmk1
MAP kinase
Signal transduction
Yes
No
fgb1
Gb subunit
Signal transduction
Yes
No
Signal transduction
Yes
Yes
fmk1+fgb1
pacC
Transcription factor
Ambient pH response
No
Yes
fpr1
PR-1 protein family
Unknown
No
Yes
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
4 experts covering 3 species
Plant resistance / defence genes
16 experts covering 15 interaction types
Plant bacterial effector genes
3 experts
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, evolutionary
biologists and bioinformaticians
Many thanks to
Wheat Pathogenesis
Thomas Baldwin*
Martin Urban
Kim Hammond-Kosack
John Antoniw
John Keon
John Lucas
Jason Rudd
Bioinformatics and
Text mining
Rainer Winnenburg
Jacob Koehler
Chris Rawlings
Other beta testers
Darren Soanes
Nick Talbot
*