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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 *