April 2006 Kim Hammond-Kosack Wheat Pathogenesis Programme Jacob Koehler Bioinformatics and Biomaths Division PHI-base

A database containing expertly curated molecular and biological information on genes proven to affect the outcome of pathogen-host interactions Winnenburg, Baldwin et al., (2006) Nucleic Acids Research 34: 459 – 465 Balwin, Winnenburg et al., (2006) Mol. Plant Microbe Interact (accepted)

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*) PubMed 2677 Web of Science 2803

f, g b a 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 albicansCandida glabrata Fusarium ear blight

What is the cause of pathogenicity ? Novel genes Gene loss Selective gene regulation Saprophytes Pathogens Plant pathogens Animal pathogens

Immuno-compromised humans Plant pathogens Human pathogens To finish Healthy plants

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 Monocot/Dicot plant Comments Pathway No effect

405 entries for genes from plant, fungal and animal attacking fungi and Oomycetes Version 2.1 (Jan 06) 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 peer-reviewed publications only

Where do you publish ? 52% of PHI-base entries were recovered from 5 journals Molecular Plant-Microbe Interactions Molecular Microbiology Infection and Immunity The Plant Cell Eukaryotic 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 Oomycetes which infect plant or animal hosts Plant Pathogens* * Number of distinct species Animal Pathogens*

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

Candida albicans – Secreted Aspartyl Proteinases

Ortoneda et al. (2004) Infect. Immun. 72: x 10 7 conidia The Fusarium oxysporum multihost model: isolate 4287 infects tomato plants and immunodepressed mice 20 mm LungHeart

Role of Fusarium oxysporum genes in virulence on plant and mammalian hosts Biological functionGeneDescription Signal transductionfmk1MAP kinase Signal transductionfgb1 G  subunit Ambient pH responsepacCTranscription factor Unknownfpr1PR-1 protein family fmk1+fgb1 Yes No Yes Required on plants No Yes No Yes Required on 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 genes 3 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, evolutionary biologists and bioinformaticians

Thomas Baldwin* Martin Urban Kim Hammond-Kosack Many thanks to John Antoniw John Keon John Lucas Jason Rudd Rainer Winnenburg Jacob Koehler Chris Rawlings * Other beta testers Darren Soanes Nick Talbot Wheat Pathogenesis Bioinformatics and Text mining