Gene Ontology and the annotation of pathogen genomes: the case of Candida albicans.

The Gene Ontology (GO) is a structured controlled vocabulary developed to describe the roles and locations of gene products in a consistent manner and in a way that can be shared across organisms. The unicellular fungus Candida albicans is similar in many ways to the model organism Saccharomyces cerevisiae but, as both a commensal and a pathogen of humans, differs greatly in its lifestyle. With an expanding at-risk population of immunosuppressed patients, increased use of invasive medical procedures, the increasing prevalence of drug resistance and the emergence of additional Candida species as serious pathogens, it has never been more crucial to improve our understanding of Candida biology to guide the development of better treatments. In this brief review, we examine the importance of GO in the annotation of C. albicans gene products, with a focus on those involved in pathogenesis. We also discuss how sequence information combined with GO facilitates the transfer of knowledge across related species and the challenges and opportunities that such an approach presents.

[1]  T. Calandra,et al.  Bench-to-bedside review: Candida infections in the intensive care unit , 2008, Critical care.

[2]  David Botstein,et al.  GO: : TermFinder--open source software for accessing Gene Ontology information and finding significantly enriched Gene Ontology terms associated with a list of genes , 2004, Bioinform..

[3]  Xiaomin Zhao,et al.  Unequal contribution of ALS9 alleles to adhesion between Candida albicans and human vascular endothelial cells. , 2007, Microbiology.

[4]  Hervé Hogues,et al.  Transcriptional Rewiring of Fungal Galactose-Metabolism Circuitry , 2007, Current Biology.

[5]  Alexander D. Johnson,et al.  Genetics of Candida albicans, a diploid human fungal pathogen. , 2007, Annual review of genetics.

[6]  Gene Ontology (GO) for Microbe–Host Interactions and Its Use in Ongoing Annotation of Three Pseudomonas syringae Genomes via the Pseudomonas–Plant Interaction (PPI) Web Site , 2008 .

[7]  Silke Schelenz,et al.  Management of candidiasis in the intensive care unit. , 2008, The Journal of antimicrobial chemotherapy.

[8]  M. Ghannoum,et al.  Candida biofilm: a well-designed protected environment. , 2005, Medical mycology.

[9]  K. Nickerson,et al.  Quorum Sensing in Dimorphic Fungi: Farnesol and Beyond , 2006, Applied and Environmental Microbiology.

[10]  Judith Berman,et al.  Candida albicans: A molecular revolution built on lessons from budding yeast , 2002, Nature Reviews Genetics.

[11]  Manuel A. S. Santos,et al.  Evolution of pathogenicity and sexual reproduction in eight Candida genomes , 2009, Nature.

[12]  André Nantel,et al.  Transcription factor substitution during the evolution of fungal ribosome regulation. , 2008, Molecular cell.

[13]  J. Lopez-Ribot,et al.  Use of a Genetically Engineered Strain To Evaluate the Pathogenic Potential of Yeast Cell and Filamentous Forms during Candida albicans Systemic Infection in Immunodeficient Mice , 2007, Infection and Immunity.

[14]  H. Rogers,et al.  Natural resistance, iron and infection: a challenge for clinical medicine. , 2006, Journal of medical microbiology.

[15]  Sandrine Dudoit,et al.  Novel Low Abundance and Transient RNAs in Yeast Revealed by Tiling Microarrays and Ultra High–Throughput Sequencing Are Not Conserved Across Closely Related Yeast Species , 2008, PLoS genetics.

[16]  George Newport,et al.  The diploid genome sequence of Candida albicans. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[17]  K. Ohlsen,et al.  Environmental Induction of White–Opaque Switching in Candida albicans , 2008, PLoS pathogens.

[18]  C. d’Enfert Biofilms and their role in the resistance of pathogenic Candida to antifungal agents. , 2006, Current drug targets.

[19]  M. Schaller,et al.  Hydrolytic enzymes as virulence factors of Candida albicans , 2005, Mycoses.

[20]  Marcelo D. Vinces,et al.  Contributions of hyphae and hypha‐co‐regulated genes to Candida albicans virulence , 2005, Cellular microbiology.

[21]  R. Wenzel,et al.  Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study. , 2004, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[22]  W. Huh,et al.  Characterization of the gene family encoding alternative oxidase from Candida albicans. , 2001, The Biochemical journal.

[23]  P. Williams,et al.  Candida albicans CFL1 encodes a functional ferric reductase activity that can rescue a Saccharomyces cerevisiae fre1 mutant. , 2000, Microbiology.

[24]  K. Lewis Multidrug tolerance of biofilms and persister cells. , 2008, Current topics in microbiology and immunology.

[25]  Christina A. Cuomo,et al.  Assembly of the Candida albicans genome into sixteen supercontigs aligned on the eight chromosomes , 2007, Genome Biology.

[26]  D. Diogo,et al.  Genotypic Evolution of Azole Resistance Mechanisms in Sequential Candida albicans Isolates , 2007, Eukaryotic Cell.

[27]  Annette M. Cashmore,et al.  Candida albicans CFL 1 encodes a functional ferric reductase activity that can rescue a Saccharomyces cerevisiae fre 1 mutant , 2022 .

[28]  M. Whiteway,et al.  Candida morphogenesis and host-pathogen interactions. , 2004, Current opinion in microbiology.

[29]  J. Berman,et al.  An isochromosome confers drug resistance in vivo by amplification of two genes, ERG11 and TAC1 , 2008, Molecular microbiology.

[30]  S. Noble,et al.  Strains and Strategies for Large-Scale Gene Deletion Studies of the Diploid Human Fungal Pathogen Candida albicans , 2005, Eukaryotic Cell.

[31]  C. Kumamoto Niche-specific gene expression during C. albicans infection. , 2008, Current opinion in microbiology.

[32]  J. Berman,et al.  Aneuploidy and Isochromosome Formation in Drug-Resistant Candida albicans , 2006, Science.

[33]  Richard D Klausner,et al.  Reductive iron uptake by Candida albicans: role of copper, iron and the TUP1 regulator. , 2002, Microbiology.

[34]  D. Howard Iron gathering by zoopathogenic fungi. , 2004, FEMS immunology and medical microbiology.

[35]  A. Johnson,et al.  Mating in Candida albicans and the search for a sexual cycle. , 2005, Annual review of microbiology.

[36]  E. Rustchenko Chromosome instability in Candida albicans. , 2007, FEMS yeast research.

[37]  J. Heitman,et al.  Sex and virulence of human pathogenic fungi. , 2007, Advances in genetics.

[38]  Gerald R. Fink,et al.  Transcriptional Response of Candida albicans upon Internalization by Macrophages , 2004, Eukaryotic Cell.

[39]  J. Berman,et al.  The distinct morphogenic states of Candida albicans. , 2004, Trends in microbiology.

[40]  A. Regev,et al.  Revisiting the Saccharomyces cerevisiae predicted ORFeome. , 2008, Genome research.

[41]  G. Vilaire,et al.  Iron Acquisition from Transferrin by Candida albicans Depends on the Reductive Pathway , 2005, Infection and Immunity.

[42]  M. Murphy,et al.  Characterization of the mitochondrial respiratory pathways in Candida albicans. , 2002, Biochimica et biophysica acta.

[43]  A. Mitchell,et al.  How to build a biofilm: a fungal perspective. , 2006, Current opinion in microbiology.

[44]  Giorgio Valle,et al.  The Gene Ontology project in 2008 , 2007, Nucleic Acids Res..

[45]  M. Ramsdale,et al.  MNL1 regulates weak acid-induced stress responses of the fungal pathogen Candida albicans. , 2008, Molecular biology of the cell.

[46]  A. Mitchell,et al.  Genetics and genomics of Candida albicans biofilm formation , 2006, Cellular microbiology.

[47]  T. Warner,et al.  Differential Candida albicans lipase gene expression during alimentary tract colonization and infection. , 2005, FEMS microbiology letters.

[48]  N. Gow,et al.  Candida albicans genome sequence: a platform for genomics in the absence of genetics , 2004, Genome Biology.

[49]  Sven Bergmann,et al.  Rewiring of the Yeast Transcriptional Network Through the Evolution of Motif Usage , 2005, Science.

[50]  R. Akins An update on antifungal targets and mechanisms of resistance in Candida albicans. , 2005, Medical mycology.

[51]  Alexander D. Johnson,et al.  Rfg1, a Protein Related to the Saccharomyces cerevisiae Hypoxic Regulator Rox1, Controls Filamentous Growth and Virulence in Candida albicans , 2001, Molecular and Cellular Biology.

[52]  S. Kelly,et al.  Molecular basis of resistance to azole antifungals. , 2002, Trends in molecular medicine.

[53]  Po-Ren Hsueh,et al.  Current challenges in the management of invasive fungal infections , 2008, Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy.

[54]  P. T. Magee,et al.  Through a glass opaquely: the biological significance of mating in Candida albicans. , 2004, Current opinion in microbiology.

[55]  D. Soll Mating-type locus homozygosis, phenotypic switching and mating: a unique sequence of dependencies in Candida albicans. , 2004, BioEssays : news and reviews in molecular, cellular and developmental biology.

[56]  K. Wolfe,et al.  Rewiring the transcriptional regulatory circuits of cells , 2004, Genome Biology.

[57]  B. Hube,et al.  Secreted lipases of Candida albicans: cloning, characterisation and expression analysis of a new gene family with at least ten members , 2000, Archives of Microbiology.

[58]  H. Fukuhara,et al.  NADH dehydrogenase subunit genes in the mitochondrial DNA of yeasts , 1994, Journal of bacteriology.

[59]  M. Whiteway,et al.  Morphogenesis in Candida albicans. , 2007, Annual review of microbiology.

[60]  D. Hogan Talking to Themselves: Autoregulation and Quorum Sensing in Fungi , 2006, Eukaryotic Cell.

[61]  M. Gerstein,et al.  The Transcriptional Landscape of the Yeast Genome Defined by RNA Sequencing , 2008, Science.

[62]  Nancy F. Hansen,et al.  Genomic evidence for a complete sexual cycle in Candida albicans , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[63]  Gene Ontology Consortium,et al.  The Gene Ontology (GO) project in 2006 , 2005, Nucleic Acids Res..

[64]  Wolfgang Huber,et al.  A high-resolution map of transcription in the yeast genome. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[65]  Xiaomin Zhao,et al.  Discovering the secrets of the Candida albicans agglutinin-like sequence (ALS) gene family--a sticky pursuit. , 2008, Medical mycology.

[66]  Erik L. L. Sonnhammer,et al.  Inparanoid: a comprehensive database of eukaryotic orthologs , 2004, Nucleic Acids Res..

[67]  M. Ruggero,et al.  Similarity of Traveling-Wave Delays in the Hearing Organs of Humans and Other Tetrapods , 2007, Journal for the Association for Research in Otolaryngology.

[68]  J. Bartlett Nosocomial bloodstream infections in US hospitals: Analysis of 24,179 cases from a prospective nationwide surveillance study , 2004 .

[69]  M. Pfaller,et al.  Epidemiology of Invasive Candidiasis: a Persistent Public Health Problem , 2007, Clinical Microbiology Reviews.

[70]  R. Bennett,et al.  Completion of a parasexual cycle in Candida albicans by induced chromosome loss in tetraploid strains , 2003, The EMBO journal.

[71]  Alexander D. Johnson,et al.  The Parasexual Cycle in Candida albicans Provides an Alternative Pathway to Meiosis for the Formation of Recombinant Strains , 2008, PLoS biology.

[72]  W. Huh,et al.  Molecular Cloning and Functional Expression of Alternative Oxidase from Candida albicans , 1999, Journal of bacteriology.

[73]  B. Hube,et al.  Candida albicans proteinases and host/pathogen interactions , 2004, Cellular microbiology.

[74]  Mingchun Li,et al.  Candida albicans Ferric Reductases Are Differentially Regulated in Response to Distinct Forms of Iron Limitation by the Rim101 and CBF Transcription Factors , 2008, Eukaryotic Cell.

[75]  M. Hostetter,et al.  Involvement of Candida albicans NADH dehydrogenase complex I in filamentation. , 2002, Fungal genetics and biology : FG & B.

[76]  K. Arastéh,et al.  Candida infection in HIV positive patients 1985–2007 , 2008, Mycoses.

[77]  Marek S. Skrzypek,et al.  Sequence resources at the Candida Genome Database , 2006, Nucleic Acids Res..

[78]  M. Whiteway,et al.  Analysis of PRA1 and Its Relationship to Candida albicans- Macrophage Interactions , 2008, Infection and Immunity.

[79]  A. E. Tsong,et al.  Evolution of alternative transcriptional circuits with identical logic , 2006, Nature.

[80]  M. Whiteway,et al.  Msn2- and Msn4-Like Transcription Factors Play No Obvious Roles in the Stress Responses of the Fungal Pathogen Candida albicans , 2004, Eukaryotic Cell.

[81]  M. Hattori,et al.  A large-scale full-length cDNA analysis to explore the budding yeast transcriptome , 2006, Proceedings of the National Academy of Sciences.