This database contains expertly curated molecular and biological information on genes proven to affect the outcome of pathogen-host interactions. Information is also given on the target sites of some anti-infective chemistries.
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DESCRIPTION OF PHI-BASE

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
Topic areas: original research articles describing single gene function studies and large scale forward genetics screens; characterisation of EST collections; full and partial genome annotation; protein-protein interaction mapping; inter-comparison of specific gene mutants within and between species; bioinformatics analysis; other databases on interactions and review articles.

Yang et al (2011). Genomic and proteomic analyses of the fungus Arthrobotrys oligospora provide insights into nematode-trap formation. Plos Pathogens. doi: 10.1371/journal.ppat.1002179

Lucas (2011). Advances in plant disease and pest management. Journal of Agricultural Science. doi: 10.1017/s0021859610000997

Kozhenkov et al (2011). BiologicalNetworks--tools enabling the integration of multi-scale data for the host-pathogen studies. BMC Syst Biol. doi: 10.1186/1752-0509-5-7

Gao et al (2011). Genome sequencing and comparative transcriptomics of the model entomopathogenic fungi Metarhizium anisopliae and M. acridum. Plos Genetics. doi: 10.1371/journal.pgen.1001264

Driscoll et al (2011). Integration and visualization of host-pathogen data related to infectious diseases. Bioinformatics. doi: 10.1093/bioinformatics/btr391

Doehlemann et al (2011). Two linked genes encoding a secreted effector and a membrane protein are essential for Ustilago maydis-induced tumour formation. Molecular Microbiology. doi: 10.1111/j.1365-2958.2011.07728.x

van de Wouw and Howlett (2011). Fungal pathogenicity genes in the age of 'omics'. Mol Plant Pathol. doi: 10.1111/j.1364-3703.2010.00680.x

Antoniw et al (2011). OmniMapFree: A new tool to visualise and explore sequenced genomes. BMC Bioinformatics. doi: 10.1186/1471-2105-12-447

Sintchenko (2010). Informatics for infectious disease research and control. in: Infectious Disease Informatics. doi: 10.1007/978-1-4419-1327-2_1

Sanchez-Rodriguez et al (2010). The Potential for pathogenicity was present in the ancestor of the Ascomycete subphylum Pezizomycotina. BMC Evolutionary Biology. doi: 10.1186/1471-2148-10-318

Lowe et al (2010). A combined (1)H nuclear magnetic resonance and electrospray ionization mass spectrometry analysis to understand the basal metabolism of plant-pathogenic Fusarium spp. Molecular Plant-Microbe Interactions. doi: 10.1094/mpmi-04-10-0092

Kumar and Nanduri (2010). HPIDB - a unified resource for host-pathogen interactions. BMC Bioinformatics. doi: 10.1186/1471-2105-11-s6-s16

K. et al (2010). Combining ChIP-chip and expression profiling to model the MoCRZ1 mediated circuit for Ca(2+)/calcineurin signaling in the rice blast fungus. Plos Pathogens. doi: 10.1371/journal.ppat.1000909

Javier Fernandez-Acero et al (2010). 2-DE proteomic approach to the Botrytis cinerea secretome induced with different carbon sources and plant-based elicitors. Proteomics. doi: 10.1002/pmic.200900408

Flower et al (2010). Computer aided selection of candidate vaccine antigens. Immunome research. doi: 10.1186/1745-7580-6-S2-S1

Baldwin et al (2010). A partial chromosomal deletion caused by random plasmid integration resulted in a reduced virulence phenotype in Fusarium graminearum. Molecular Plant-Microbe Interactions. doi: 10.1094/mpmi-23-8-1083

Zhao et al (2009). FPPI: Fusarium graminearum protein-protein interaction database. Journal of Proteome Research. doi: 10.1021/pr900415b

Takahara et al (2009). Flow cytometric purification of Colletotrichum higginsianum biotrophic hyphae from Arabidopsis leaves for stage-specific transcriptome analysis. Plant Journal. doi: 10.1111/j.1365-313X.2009.03896.x

Soderlund (2009). Computational techniques for elucidating plant-pathogen interactions from large-scale experiments on fungi and oomycetes. Briefings in Bioinformatics. doi: 10.1093/bib/bbp053

Oeser et al (2009). Expressed sequence tags from the flower pathogen Claviceps purpurea. Mol Plant Pathol. doi: 10.1111/j.1364-3703.2009.00560.x

Li et al (2009). Towards a comprehensive HBV-human interaction map. 2009 International Joint Conference on Bioinformatics

Systems Biology and Intelligent Computing Proceedings.
doi: 10.1109/ijcbs.2009.49

Korves and Colosimo (2009). Controlled vocabularies for microbial virulence factors. Trends in Microbiology. doi: 10.1016/j.tim.2009.04.002

Huser et al (2009). Discovery of pathogenicity genes in the crucifer anthracnose fungus Colletotrichum higginsianum using random insertional mutagenesis. Molecular Plant-Microbe Interactions. doi: 10.1094/mpmi-22-2-0143

Soanes et al (2008). Comparative genome analysis of filamentous fungi reveals gene family expansions associated with fungal pathogenesis. Plos One. doi: 10.1371/journal.pone.0002300

Kleemann et al (2008). Identification of soluble secreted proteins from appressoria of Colletotrichum higginsianum by analysis of expressed sequence tags. Microbiology-Sgm. doi: 10.1099/mic.0.2007/014944-0

Jeon et al (2008). Functional genomics in the rice blast fungus to unravel the fungal pathogenicity. Journal of Zhejiang University-Science B. doi: 10.1631/jzus.B0860014

He et al (2008). The prediction of protein-protein interaction networks in rice blast fungus. Bmc Genomics. doi: 10.1186/1471-2164-9-519

Haegi et al (2008). Histological and molecular analysis of Rdg2a barley resistance to leaf stripe. Mol Plant Pathol. doi: 10.1111/j.1364-3703.2008.00479.x

Frezal and Leblois (2008). Four years of DNA barcoding: Current advances and prospects. Infection Genetics and Evolution. doi: 10.1016/j.meegid.2008.05.005

Bolton and Thomma (2008). The complexity of nitrogen metabolism and nitrogen-regulated gene expression in plant pathogenic fungi. Physiological and Molecular Plant Pathology. doi: 10.1016/j.pmpp.2008.07.001

Yockteng et al (2007). Expressed sequences tags of the anther smut fungus Microbotryum violaceum identify mating and pathogenicity genes. BMC Genomics. doi: 10.1186/1471-2164-8-272

Xiang et al (2007). PHIDIAS: a pathogen-host interaction data integration and analysis system. Genome Biol. doi: 10.1186/gb-2007-8-7-r150

Williamson et al (2007). Botrytis cinerea: the cause of grey mould disease. Mol Plant Pathol. doi: 10.1111/j.1364-3703.2007.00417.x

van der Does and Rep (2007). Virulence genes and the evolution of host specificity in plant-pathogenic fungi. Mol Plant Microbe Interact. doi: 10.1094/MPMI-20-10-1175

van Baarlen et al (2007). Molecular mechanisms of pathogenicity: how do pathogenic microorganisms develop cross-kingdom host jumps? FEMS Microbiology Reviews. doi: 10.1111/j.1574-6976.2007.00065.x

Staal and Dixelius (2007). Tracing the ancient origins of plant innate immunity. Trends in Plant Science. doi: 10.1016/j.tplants.2007.06.014

Jeon et al (2007). Genome-wide functional analysis of pathogenicity genes in the rice blast fungus. Nature Genetics. doi: 10.1038/ng2002

Hane et al (2007). Dothideomycete-plant interactions illuminated by genome sequencing and EST analysis of the wheat pathogen Stagonospora nodorum. Plant Cell. doi: 10.1105/tpc.107.052829

DiGuistini et al (2007). Generation and annotation of lodgepole pine and oleoresin-induced expressed sequences from the blue-stain fungus Ophiostoma clavigeruma mountain pine beetle-associated pathogen. Fems Microbiology Letters. doi: 10.1111/j.1574-6968.2006.00565.x

Dickman (2007). Subversion or coersion? Pathogenic deteminants in fungal phytopathogens. Fungal Biology Reviews. doi: 10.1016/j.fbr.2007.06.003

Davies et al (2007). Using databases and data mining in vaccinology. Expert opinion on Drug Discovery. doi: 10.1517/17460441.2.1.19

Bouzidi et al (2007). Expressed sequence tags from the oomycete Plasmopara halstedii an obligate parasite of the sunflower. BMC Microbiol. doi: 10.1186/1471-2180-7-110

Sexton and Howlett (2006). Parallels in fungal pathogenesis on plant and animal hosts. Eukaryotic cell. doi: 10.1128/ec.00277-06

O'Connell and Panstruga (2006). Tete a tete inside a plant cell: establishing compatibility between plants and biotrophic fungi and oomycetes. New Phytologist. doi: 10.1111/j.1469-8137.2006.01829.x

Kohler et al (2006). Ontology based text indexing and querying for the semantic web. Knowledge-Based Systems. doi: 10.1016/j.knosys.2006.04.015

Kohler et al (2006). Graph-based analysis and visualization of experimental results with ONDEX. Bioinformatics. doi: 10.1093/bioinformatics/bt/081




ORAL PRESENTATIONS ON PHI-BASE

2011
J. Lucas, J. Grzebyta, M. Urban, M. Saqi and K. E. Hammond-Kosack. The pathogen-host interactions database: new developments. The Center for Biomedical Informatics, State University of Campinas, Brazil, 16th Dec 2011

J. Grzebyta, A. Splendiani, M. Urban, K. E. Hammond-Kosack, C. J. Rawlings and M. Saqi. Towards a computantional representation of host-pathogen interaction networks. Second SICSA Workshop on Biological Networks, 21st Oct 2011

M. Saqi, Andrea Splendiani, J. Grzebyta, M. Urban, M. Defoin-Platel, E. Janowska-Sejda, C. Rawlings and K. E. Hammond-Kosack. Gene discovery for improved resistance to pests and pathogens. Monogram workshop Session V, Sutton Bonnington, Nottingham UK, 11-13th April 2011

2010
E. Janowska-Sejda , M. Defoin-Platel, K. E. Hammond-Kosack , M. Urban , S. Tsoka and M. Saqi. A systems biology approach to explore host-pathogen interactions through the use and further development of PHI-base database and newly sequenced pathogen genomes. Molecular Biology of Plant Pathogens Conference , Exeter, UK, 17th - 19th September 2010.

J. Grzebyta, A. Splendiani, M. Urban, K. E. Hammond-Kosack, C. J. Rawlings and M. Saqi. PHI-base 4: A new approach for capturing host-pathogen interactions. Molecular Biology of Plant Pathogens Conference , Exeter, UK, 17th - 19th September 2010.

K. Hammond-Kosack, M. Urban, J. Rudd, H. Cools and J. Antoniw. The plant pathogen 'omics world where is it taking us in developing novel options to control fungal diseases ? 9th International Mycology Congress (IMC9), Edinburgh, UK, 1-6 August 2010

A. Beacham, J. Antoniw, A. Freeman, M. Urban, K. Hammond-Kosack. The identification of a virulence factor enriched micro-region in the Fusarium graminearum genome. 9th International Mycology Congress (IMC9), Edinburgh, UK, 1-6 August 2010

2009
K. Hammond-Kosack, M. Urban, A. Beacham, N. Brown, C. Cavanet, M. Saqi, C. Rawlings and J. Antoniw. Using genomics to reveal the enemy's weapons. BA festival of Science, University of Surrey, Guildford, Sept 2009

2008
K. Hammond-Kosack, T. Baldwin, A. Beacham, M. Urban, R. Winnenburg, J. Koehler, M. Saqi and C. Rawlings. Novel ways to explore sequenced fungal genomes. European Fungal Genetics Conference, Edinburgh, UK April 2008

A. Beacham, C. Cavanet, J. Taubert, M. Urban, J. Antoniw, C. Rawlings and K. 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

K. Hammond-Kosack, T. Baldwin, M. Urban, R. Winnenburg, J. Koehler, M. Saqi and C. Rawlings. The plant pathogen 'omics world - where is it taking us? EBI-EMBL joint workshop, Cambridge, UK Oct 2008

K. Hammond-Kosack and J. 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

K. Hammond-Kosack, M. Urban, A. Beacham, N. Brown, C. Cavanet, M. Saqi, C. Rawlings and J. 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
K. Hammond-Kosack, M. Urban, J. Rudd and K. 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
J. Köhler, R. Winnenburg, C. Rawlings, T. Baldwin, M. Urban and K. Hamond-Kosack
Pathogen-Host Interactions Database (Phi-Base)
COGEME interest group meeting, 7th - 8th November 2006, Chancellors Hotel and Conference Centre, Manchester, UK

T. K. Baldwin, R. Winnenburg, M. Urban, C. Rawlings, J. Köhler and K. 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
T. Baldwin, R. Winnenburg, J. Köhler, M. Urban and K. 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)

T. Baldwin, R. Winnenburg, J. Köhler, M. Urban and K. 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 2011 ONWARDS

PHASE 1 - Link the new ENSEMBL genome browser interface to the contents of PHI-base in a gene centric manner - achieved October 2011

PHASE 2 - Train others in the data curation process to clear the peer-reviewed paper backlog - on track

PHASE 3 - Development of a prototype self-entry data curation interface

PHASE 4 - Beta testing of the curation interface for several species

PHASE 5 - Launch the new database scheme as PHI-base version 4

PHASE 6 - 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.


Ondex Example



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

Goodwin et al (2011). Finished genome of the fungal wheat pathogen Mycosphaerella graminicola reveals dispensome structure, chromosome plasticity, and stealth pathogenesis. PLoS Genet. doi: 10.1371/journal.pgen.1002070

Spanu et al (2010). Genome expansion and gene loss in powdery mildew fungi reveal tradeoffs in extreme parasitism. Science. doi: 10.1126/science.1194573

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.broadinstitute.org/fungal genome initiative


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



Reviews on Pathogenicity

van de Wouw and Howlett (2011). Fungal pathogenicity genes in the age of 'omics'. Mol Plant Pathol. doi: 10.1111/j.1364-3703.2010.00680.x

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).



Version: 3.3 Last revision: 10/01/12
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