PHI-base is a web-accessible database that catalogues experimentally verified pathogenicity, virulence and effector genes from fungal, Oomycete and bacterial pathogens, which infect animal, plant, fungal and insect hosts. PHI-base is therfore an invaluable resource in the discovery of genes in medically and agronomically important pathogens, which may be potential targets for chemical intervention. In collaboration with the FRAC team, PHI-base also includes antifungal compounds and their target genes.

Each entry in PHI-base is curated by domain experts and is supported by strong experimental evidence (gene disruption experiments, STM etc), as well as literature references in which the original experiments are described. Each gene in PHI-base is presented with its nucleotide and deduced amino acid sequence, as well as a detailed description of the predicted protein's function during the host infection process. To facilitate data interoperability, we have annotated genes using controlled vocabularies and links to external sources (Gene Ontology terms, EC Numbers, NCBI taxonomy, EMBL, PubMed and FRAC).

PUBLICATIONS ON PHI-BASE

Winnenburg, R., Urban, M., Beacham, A., Baldwin, T.K., Holland, S., Lindeberg, M., Hansen, H., Rawlings, C., Hammond-Kosack, K.E., and Kohler, J. (2008). PHI-base update: additions to the pathogen host interaction database. Nucleic Acids Res 36, D572-576.
PubMed:17942425

Baldwin, T.K., Winnenburg, R., Urban, M., Rawlings, C., Köhler, J. and Hammond-Kosack, K.E. 2006. The Pathogen-Host Interactions database (PHI-base) provides insights into generic and novel themes of pathogenicity. Mol Plant Microbe Interact. 19(12):1451-62
PubMed:17153929

Winnenburg, R., Baldwin, T.K., Urban, M., Rawlings, C., Köhler, J. and Hammond-Kosack, K.E. 2006. PHI-base: a new database for pathogen host interactions. Nucleic Acids Research. 34(Database issue):D459-D464
PubMed:16381911


PUBLICATIONS CITING PHI-BASE

Sexton AC, Howlett BJ. 2006. Parallels in fungal pathogenesis on plant and animal hosts. Eukaryot Cell. 5(12):1941-9
PubMed:17041185

O'Connell RJ, Panstruga R. 2006. Tete a tete inside a plant cell: establishing compatibility between plants and biotrophic fungi and oomycetes. New Phytol. 171(4):699-718
PubMed:16918543

van Baarlen P, van Belkum A, Summerbell RC, Crous PW, Thomma BP. 2007. Molecular mechanisms of pathogenicity: how do pathogenic microorganisms develop cross-kingdom host jumps? FEMS Microbiol Rev. 31(3):239-77
PubMed:17326816

Davies MN, Guan P, Blythe MJ, Salomon J, Toseland CP, Hattotuwagama C, Walshe V, Doytchinova IA, Flower DR. 2007. Using databases and data mining in vaccinology. Expert Opinion on Drug Discovery 2(1):19-35

He et al (2008). The prediction of protein-protein interaction networks in rice blast fungus. Bmc Genomics. 9, 519.
PubMed:18976500

Michielse, C.B., and Rep, M. (2009). Pathogen profile update: Fusarium oxysporum. Molecular Plant Pathology 10, 311-324.
PubMed:19400835


PUBLICATIONS WHICH USED PHI-BASE FOR THE IDENTIFICATION OF PATHOGENICITY GENES

Jeon J, Park SY, Chi MH, Choi J, Park J, Rho HS, Kim S, Goh J, Yoo S, Choi J, Park JY, Yi M, Yang S, Kwon MJ, Han SS, Kim BR, Khang CH, Park B, Lim SE, Jung K, Kong S, Karunakaran M, Oh HS, Kim H, Kim S, Park J, Kang S, Choi WB, Kang S, Lee YH. 2007. Genome-wide functional analysis of pathogenicity genes in the rice blast fungus. Nat Genet. 39(4):561-5
PubMed:17353894

Scott DiGuistini, Steven G. Ralph, Young W. Lim, Robert Holt, Steven Jones, Jörg Bohlmann, Colette Breuil. 2007. Generation and annotation of lodgepole pine and oleoresin-induced expressed sequences from the blue-stain fungus Ophiostoma clavigerum, a Mountain Pine Beetle-associated pathogen FEMS Microbiology Letters. 267 (2):151-158
PubMed:17328114

Oeser et al (2009). Expressed sequence tags from the flower pathogen Claviceps purpurea. Molecular Plant Pathology. 10, 665-684.
PubMed:19694956

Takahara et al (2009). Flow cytometric purification of Colletotrichum higginsianum biotrophic hyphae from Arabidopsis leaves for stage-specific transcriptome analysis. Plant J 59, 672-683
PubMed:19392696

Kleemann et al (2008). Identification of soluble secreted proteins from appressoria of Colletotrichum higginsianum by analysis of expressed sequence tags. Microbiology 154, 1204-1217.
PubMed:18375813

Haegi et al (2008). Histological and molecular analysis of Rdg2a barley resistance to leaf stripe. Molecular Plant Pathology. 9, 463-478.
PubMed:18705861

Frezal et al (2008). Four years of DNA barcoding: current advances and prospects. Infect Genet Evol . 8, 727-736. Pubmed 18573351
PubMed:18573351

Bouzidi et al (2007). Expressed Sequence Tags from the oomycete Plasmopara halstedii, an obligate parasite of the sunflower. BMC Microbiol. 7, 110. Pubmed 18062809
PubMed:18062809

Yockteng et al (2007). Expressed sequences tags of the anther smut fungus, Microbotryum violaceum, identify mating and pathogenicity genes. Bmc Genomics. 8, 272.
PubMed:17692127

Staal, J., and Dixelius, C. (2007). Tracing the ancient origins of plant innate immunity. Trends Plant Sci . 12, 334-342.
PubMed:17644465

Xiang et al (2007). PHIDIAS: a pathogen-host interaction data integration and analysis system. Genome Biol. 8, R150.
PubMed:17663773

van Baarlen et al (2007). Molecular mechanisms of pathogenicity: how do pathogenic microorganisms develop cross-kingdom host jumps? FEMS Microbiol Rev. 31, 239-277.
PubMed:17326816

Hane et al (2007). Dothideomycete plant interactions illuminated by genome sequencing and EST analysis of the wheat pathogen Stagonospora nodorum. Plant Cell. 19, 3347-3368.
PubMed:18024570

Bolton, M.D., and Thomma, B.P.H.J. (2008). The complexity of nitrogen metabolism and nitrogen-regulated gene expression in plant pathogenic fungi. Physiological and Molecular Plant Pathology. 72, 104-110. Pubmed: not available. DOI: 10.1016/j.pmpp.2008.07.001


ORAL PRESENTATIONS ON PHI-BASE

2009
Kim Hammond-Kosack, Martin Urban, Andrew Beacham, Neil Brown, Catherine Cavanet, Mansoor Saqi, Chris Rawlings and John Antoniw Using genomics to reveal the enemy.s weapons. BA festival of Science, University of Surrey, Guildford, Sept 2009

2008
Kim Hammond-Kosack, Thomas Baldwin, Andrew Beacham, Martin Urban, Rainer Winnenburg, Jacob Koehler, Mansoor Saqi and Chris Rawlings. Novel ways to explore sequenced fungal genomes. European Fungal Genetics Conference, Edinburgh, UK April 2008

Andrew Beacham, Catherine Cavanet, Jan Taubert, Martin Urban, John Antoniw, Chris Rawlings and Kim Hammond-Kosack. Analysis of the newly sequenced Fusarium genomes using PHI-base and ONDEX. 10th International Fusarium and Fusarium genomics workshop. Alghero, Sardinia, Italy, Sept 2008

Kim Hammond-Kosack, Thomas Baldwin, Martin Urban, Rainer Winnenburg, Jacob Koehler, Mansoor Saqi and Chris Rawlings. The Plant Pathogen 'Omics world - where is it taking us? EBI-EMBL joint workshop, Cambridge, UK Oct 2008

Kim Hammond-Kosack and John Antoniw. An inter-comparison of the pathogenicity, virulence and effector gene complement of the six Dothidiomycete genomes. Dothidiomycetes genome jamboree, DOE, Joint Genome Institute, Walnut Creek, California, USA Nov 2008

Kim Hammond-Kosack, Martin Urban, Andrew Beacham, Neil Brown, Catherine Cavanet, Mansoor Saqi, Chris Rawlings and John Antoniw How can molecular genetic information on plant pathogens benefit disease management. British Society for Plant Pathology, Presidential conference, Queen Mary College, London, Dec 2008.

2007
Kim Hammond-Kosack, Martin Urban, Jason Rudd and Kostya Kanyuka Comparative genomics of pathogenesis and innate immunity. Joint Rothamsted Research - Institute of Animal Health Workshop, held at The Compton Laboratory, England, May 2007

2006
Jacob Köhler, Rainer Winnenburg, Chris Rawlings, Thomas Baldwin, Martin Urban and Kim Hamond-Kosack
Pathogen-Host Interactions Database (Phi-Base)
COGEME interest group meeting, 7th - 8th November 2006, Chancellors Hotel and Conference Centre, Manchester, UK

Thomas K. Baldwin, Rainer Winnenburg, Martin Urban, Chris Rawlings, Jacob Köhler and Kim E. Hammond-Kosack
PHI-base: A database of experimentally verified pathogenicity, virulence and effector genes in fungal and Oomycete pathogens of animals and plants
8th European Conference on Fungal Genetics in the Symposium "Mechanisms of human pathogenesis" 8th & 11th April 2006, Vienna, Austria
Online:Conference Presentation

2005
Thomas Baldwin, Rainer Winnenburg, Jacob Köhler, Martin Urban and Kim Hammond-Kosack
Bioinformatic and molecular genetic tools for identifying genes involved in pathogenicity
XVI Molecular Biology of Plant Pathogens meeting, Ambleside 19-21th September 2005
ESF-EMBO Symposium on Comparative Genomics of Eukaryotic Microorganisms, Sant Feliu de Guixols, Spain. November 2005
(Oral and poster presentations)

Thomas Baldwin, Rainer Winnenburg, Jacob Köhler, Martin Urban and Kim Hammond-Kosack
Bioinformatic and molecular genetic tools for identifying genes involved in the pathogenicity of Fusarium graminearum on wheat ears
COGEME users meeting - Manchester University November 2005
Online:(http://www.cogeme.man.ac.uk/)


FUTURE DEVELOPMENTS FOR PHI-BASE FROM 2010 ONWARDS

PHASE 1 - Development of a prototype self-entry data curation interface

PHASE 2 - Beta testing of the curation interface for several species

PHASE 3 - Development of tools to permit basic pathogen comparative analysis directly within PHI-base

We intend to show relationships between proteins in PHI-base using network representations where the nodes represent the proteins and the edges reflect the degree of sequence similarity between the proteins. The nodes in these clusters of related proteins would be colour and shape coded according to whether the pathogens were plant/animal and according to phenotype (see beneath for prototype image using the ONDEX (Kohler et al, (2006) Bioinformatics, 22:1383-90) data integration and visualisation software). The curation tool would automatically assign a new sequence to a cluster (if related) thereby allowing the annotator to view its biological context. Additionally the user would be able to select groups of related proteins and retrieve the corresponding sequences and perform multiple sequence alignments. This would allow the patterns of sequence conservation to be examined in the context of the type of pathogen and the associated phenotype.


Figure: Part of an Ondex screenshot showing a cluster of related sequences from PHI-base (triangles) coloured according to outcome (phenotype) and showing relationships to associated KEGG pathways (stars). The PHI-base proteins were clustered using MCL clustering. Some edges in the graph are not shown for increased clarity. We hope to develop a link from the proposed curation tool to an Ondex web service to allow a new putative sequence involved in a pathogen-host interaction to be assigned to a cluster (if appropriate) and the Ondex graph returned. Inspection of the graph would then allow the curator to view the context of the new sequence in relation to existing PHI-base sequences and pathway information. The tightly connected cluster are polygalacturinases (part of glycosyl hydrolase 28 family) Mappings to KEGG - include Pentose and Glucuronate interconversion, Starch and sucrose metabolism, Aminosugars metabolism. Some edges are not shown for clarity.






RELATED WORK

General Plant Pathology

Agrios, G. N. 1997. Plant Pathology. Academic Press, Inc., London.

de Bary, H. A. 1879. The Phenomenon of Symbiosis. Strasbourg.

Shaner, G., Stromberg, E. L., Lacy, G. H., Barker, K. R., and Pirone, T. P. 1992. Nomenclature and concepts of pathogenicity and virulence. Annu. Rev. Phytopathol. 30:47-66.


Sequenced Fungal and Oomycete Genomes

Tyler et al., 2006. Phytophthora genome sequences uncover evolutionary origins and mechanisms of pathogenesis. Science 313(5791):1261-6.
PubMed:16946064

Kamper et al., 2006. Insights from the genome of the biotrophic fungal plant pathogen Ustilago maydis. Nature 444(7115):97-101.
PubMed:17080091

Dean et al., 2005. The genome sequence of the rice blast fungus Magnaporthe grisea. Nature 434:980-6.
PubMed:15846337

Dietrich et al., 2004. The Ashbya gossypii genome as a tool for mapping the ancient Saccharomyces cerevisiae genome. Science 304:304-7.
PubMed:15001715

Galagan et al., 2003. The genome sequence of the filamentous fungus Neurospora crassa. Nature 422:859-68.
PubMed:12712197

Goffeau et al., 1996. Life with 6000 Genes. Science 274:546-566.
PubMed:8849441

Jones et al., 2004. The diploid genome sequence of Candida albicans. Proc. Natl. Acad. Sci. U. S. A. 101:7329-7334.
PubMed:15123810

Génolevures 2005. Genomic exploration of the hemiascomycete yeasts.
Online:http://cbi.labri.fr/Genolevures/index.php

Joint Genome Institute 2005. Eukaryotic Genomes.
Online:http://genome.jgi-psf.org/euk_cur1.html

Broad Institute 2005. Fungal Genome Initiative (FGI).
Online:http://www.broad.mit.edu/annotation/fungi/fgi/

Sanger Institute, 2005. Fungal genomes.
Online:http://www.sanger.ac.uk/Projects/Fungi/


Reviews on Pathogenicity

Ellis, J.G., Rafiqi, M., Gan, P., Chakrabarti, A., and Dodds, P.N. (2009). Recent progress in discovery and functional analysis of effector proteins of fungal and oomycete plant pathogens. Curr. Opinion in Plant Biol. 12, 399-405.
PubMed:19540152

Hogenhout, S.A., Van der Hoorn, R.A.L., Terauchi, R., and Kamoun, S. (2009). Emerging Concepts in Effector Biology of Plant-Associated Organisms. Mol. Plant-Microbe Interactions 22, 115-122.
PubMed:19132864

Stergiopoulos, I., and de Wit, P.J.G.M. (2009). Fungal Effector Proteins. Annual Rev. of Phytopathol. 47, 233-263. PMID: 19400631
PubMed:19400631

Sexton AC, Howlett BJ., 2006. Parallels in fungal pathogenesis on plant and animal hosts. Eukaryot Cell. 5(12):1941-9
PubMed:17041185

Feldbrugge, M., Kamper, J., Steinberg, G., and Kahmann, R., 2004. Regulation of mating and pathogenic development in Ustilago maydis. Curr Opin Microbiol. 7:666-72.
PubMed:15556041

Talbot, NJ, 2003. On the trail of a cereal killer: Exploring the biology of Magnaporthe grisea. Annu Rev Microbiol. 57:177-202
PubMed:14527276

Idnurm, A., and Howlett, B. J., 2001. Pathogenicity genes of phytopathogenic fungi. Mol. Plant Pathol. 2:241-255.

Laugé, R., and De Wit, P. J., 1998. Fungal avirulence genes: structure and possible functions. Fungal Genet Biol. 24:285-97.
PubMed:9756710

Knogge, W., 1996. Fungal infections of plants. Plant Cell 8:1711-1722.
PubMed:12239359


Ontologies

Torto-Alalibo, T., Collmer, C. W. and Gwinn-Giglio, M., 2009. The Plant-Associated Microbe Gene Ontology (PAMGO) Consortium: community development of new Gene Ontology terms describing biological processes involved in microbe-host interactions. BMC Microbiology 9 (Suppl I): SI. Review.
PubMed:19278549

Gene-Ontology-Consortium., 2006. The Gene Ontology (GO) project in 2006. Nucl. Acids Res. 34:D322-D326.
PubMed:16381878

PAMGO - Plant-Associated Microbe Gene Ontologies (2005)
A collaborative effort has establishment of 585 terms in the GO Biological Process ontology. Four hundred and seventy two (472) of these terms, have recently incorporated into the Biological Process ontology describe more specific processes involved in the interaction between microbes and their hosts.

Featured below are some high order terms developed by PAMGO, which can be accessed from the Gene Ontology browser (AMIGO: http://www.godatabase.org).