Saccharomyces genome database update: server architecture, pan-genome nomenclature, and external resources.

As one of the first model organism knowledgebases, Saccharomyces Genome Database (SGD) has been supporting the scientific research community since 1993. As technologies and research evolve, so does SGD: from updates in software architecture, to curation of novel data types, to incorporation of data from, and collaboration with, other knowledgebases. We are continuing to make steps toward providing the community with an S. cerevisiae pan-genome. Here, we describe software upgrades, a new nomenclature system for genes not found in the reference strain, and additions to gene pages. With these improvements, we aim to remain a leading resource for students, researchers, and the broader scientific community.

How to Use the Candida Genome Database.

The Candida Genome Database provides access to biological information about genes and proteins of several medically important Candida species. The website is organized into easily navigable pages that enable data retrieval and analysis. This chapter shows how to explore the CGD Home page and Locus Summary pages, which are the main access points to the database. It also provides a description of how to use the GO analysis tools, GO Term Finder, and GO Slim Mapper and how to browse large-scale datasets using the JBrowse genome browser. Finally, it shows how to search and retrieve data for user-defined sets of genes using the Advanced Search and Batch Download tools.

New data and collaborations at the Saccharomyces Genome Database: updated reference genome, alleles, and the Alliance of Genome Resources.

Saccharomyces cerevisiae is used to provide fundamental understanding of eukaryotic genetics, gene product function, and cellular biological processes. Saccharomyces Genome Database (SGD) has been supporting the yeast research community since 1993, serving as its de facto hub. Over the years, SGD has maintained the genetic nomenclature, chromosome maps, and functional annotation, and developed various tools and methods for analysis and curation of a variety of emerging data types. More recently, SGD and six other model organism focused knowledgebases have come together to create the Alliance of Genome Resources to develop sustainable genome information resources that promote and support the use of various model organisms to understand the genetic and genomic bases of human biology and disease. Here we describe recent activities at SGD, including the latest reference genome annotation update, the development of a curation system for mutant alleles, and new pages addressing homology across model organisms as well as the use of yeast to study human disease.

Transcriptome visualization and data availability at the Saccharomyces Genome Database.

The Saccharomyces Genome Database (SGD; www.yeastgenome.org) maintains the official annotation of all genes in the Saccharomyces cerevisiae reference genome and aims to elucidate the function of these genes and their products by integrating manually curated experimental data. Technological advances have allowed researchers to profile RNA expression and identify transcripts at high resolution. These data can be configured in web-based genome browser applications for display to the general public. Accordingly, SGD has incorporated published transcript isoform data in our instance of JBrowse, a genome visualization platform. This resource will help clarify S. cerevisiae biological processes by furthering studies of transcriptional regulation, untranslated regions, genome engineering, and expression quantification in S. cerevisiae.

Integration of macromolecular complex data into the Saccharomyces Genome Database.

Proteins seldom function individually. Instead, they interact with other proteins or nucleic acids to form stable macromolecular complexes that play key roles in important cellular processes and pathways. One of the goals of Saccharomyces Genome Database (SGD; www.yeastgenome.org) is to provide a complete picture of budding yeast biological processes. To this end, we have collaborated with the Molecular Interactions team that provides the Complex Portal database at EMBL-EBI to manually curate the complete yeast complexome. These data, from a total of 589 complexes, were previously available only in SGD's YeastMine data warehouse (yeastmine.yeastgenome.org) and the Complex Portal (www.ebi.ac.uk/complexportal). We have now incorporated these macromolecular complex data into the SGD core database and designed complex-specific reports to make these data easily available to researchers. These web pages contain referenced summaries focused on the composition and function of individual complexes. In addition, detailed information about how subunits interact within the complex, their stoichiometry and the physical structure are displayed when such information is available. Finally, we generate network diagrams displaying subunits and Gene Ontology annotations that are shared between complexes. Information on macromolecular complexes will continue to be updated in collaboration with the Complex Portal team and curated as more data become available.

Using the Candida Genome Database.

Studying Candida biology requires access to genomic sequence data in conjunction with experimental information that together provide functional context to genes and proteins, and aid in interpreting newly generated experimental data. The Candida Genome Database (CGD) curates the Candida literature, and integrates functional information about Candida genes and their products with a set of analysis tools that facilitate searching for sets of genes and exploring their biological roles. This chapter describes how the various types of information available at CGD can be searched, retrieved, and analyzed. Starting with the guided tour of the CGD Home page and Locus Summary page, this unit shows how to navigate the various assemblies of the C. albicans genome, how to use Gene Ontology tools to make sense of large-scale data, and how to access the microarray data archived at CGD, as well as visualize high-throughput sequencing data through the use of JBrowse.

Updated regulation curation model at the Saccharomyces Genome Database.

Database URL: http://www.yeastgenome.org.

Saccharomyces genome database informs human biology.

The Saccharomyces Genome Database (SGD; http://www.yeastgenome.org) is an expertly curated database of literature-derived functional information for the model organism budding yeast, Saccharomyces cerevisiae. SGD constantly strives to synergize new types of experimental data and bioinformatics predictions with existing data, and to organize them into a comprehensive and up-to-date information resource. The primary mission of SGD is to facilitate research into the biology of yeast and to provide this wealth of information to advance, in many ways, research on other organisms, even those as evolutionarily distant as humans. To build such a bridge between biological kingdoms, SGD is curating data regarding yeast-human complementation, in which a human gene can successfully replace the function of a yeast gene, and/or vice versa. These data are manually curated from published literature, made available for download, and incorporated into a variety of analysis tools provided by SGD.

Outreach and online training services at the Saccharomyces Genome Database.

The Saccharomyces Genome Database (SGD; www.yeastgenome.org ), the primary genetics and genomics resource for the budding yeast S. cerevisiae , provides free public access to expertly curated information about the yeast genome and its gene products. As the central hub for the yeast research community, SGD engages in a variety of social outreach efforts to inform our users about new developments, promote collaboration, increase public awareness of the importance of yeast to biomedical research, and facilitate scientific discovery. Here we describe these various outreach methods, from networking at scientific conferences to the use of online media such as blog posts and webinars, and include our perspectives on the benefits provided by outreach activities for model organism databases. Database URL: http://www.yeastgenome.org.

The Candida Genome Database (CGD): incorporation of Assembly 22, systematic identifiers and visualization of high throughput sequencing data.

The Candida Genome Database (CGD, http://www.candidagenome.org/) is a freely available online resource that provides gene, protein and sequence information for multiple Candida species, along with web-based tools for accessing, analyzing and exploring these data. The mission of CGD is to facilitate and accelerate research into Candida pathogenesis and biology, by curating the scientific literature in real time, and connecting literature-derived annotations to the latest version of the genomic sequence and its annotations. Here, we report the incorporation into CGD of Assembly 22, the first chromosome-level, phased diploid assembly of the C. albicans genome, coupled with improvements that we have made to the assembly using additional available sequence data. We also report the creation of systematic identifiers for C. albicans genes and sequence features using a system similar to that adopted by the yeast community over two decades ago. Finally, we describe the incorporation of JBrowse into CGD, which allows online browsing of mapped high throughput sequencing data, and its implementation for several RNA-Seq data sets, as well as the whole genome sequencing data that was used in the construction of Assembly 22.

How to Use the Candida Genome Database.

Studying Candida biology requires access to genomic sequence data in conjunction with experimental information that provides functional context to genes and proteins. The Candida Genome Database (CGD) integrates functional information about Candida genes and their products with a set of analysis tools that facilitate searching for sets of genes and exploring their biological roles. This chapter describes how the various types of information available at CGD can be searched, retrieved, and analyzed. Starting with the guided tour of the CGD Home page and Locus Summary page, this unit shows how to navigate the various assemblies of the C. albicans genome, how to use Gene Ontology tools to make sense of large-scale data, and how to access the microarray data archived at CGD.

The Saccharomyces Genome Database Variant Viewer.

The Saccharomyces Genome Database (SGD; http://www.yeastgenome.org) is the authoritative community resource for the Saccharomyces cerevisiae reference genome sequence and its annotation. In recent years, we have moved toward increased representation of sequence variation and allelic differences within S. cerevisiae. The publication of numerous additional genomes has motivated the creation of new tools for their annotation and analysis. Here we present the Variant Viewer: a dynamic open-source web application for the visualization of genomic and proteomic differences. Multiple sequence alignments have been constructed across high quality genome sequences from 11 different S. cerevisiae strains and stored in the SGD. The alignments and summaries are encoded in JSON and used to create a two-tiered dynamic view of the budding yeast pan-genome, available at http://www.yeastgenome.org/variant-viewer.

Biocuration at the Saccharomyces genome database.

Saccharomyces Genome Database is an online resource dedicated to managing information about the biology and genetics of the model organism, yeast (Saccharomyces cerevisiae). This information is derived primarily from scientific publications through a process of human curation that involves manual extraction of data and their organization into a comprehensive system of knowledge. This system provides a foundation for further analysis of experimental data coming from research on yeast as well as other organisms. In this review we will demonstrate how biocuration and biocurators add a key component, the biological context, to our understanding of how genes, proteins, genomes and cells function and interact. We will explain the role biocurators play in sifting through the wealth of biological data to incorporate and connect key information. We will also discuss the many ways we assist researchers with their various research needs. We hope to convince the reader that manual curation is vital in converting the flood of data into organized and interconnected knowledge, and that biocurators play an essential role in the integration of scientific information into a coherent model of the cell.

Literature-based gene curation and proposed genetic nomenclature for cryptococcus.

Cryptococcus, a major cause of disseminated infections in immunocompromised patients, kills over 600,000 people per year worldwide. Genes involved in the virulence of the meningitis-causing fungus are being characterized at an increasing rate, and to date, at least 648 Cryptococcus gene names have been published. However, these data are scattered throughout the literature and are challenging to find. Furthermore, conflicts in locus identification exist, so that named genes have been subsequently published under new names or names associated with one locus have been used for another locus. To avoid these conflicts and to provide a central source of Cryptococcus gene information, we have collected all published Cryptococcus gene names from the scientific literature and associated them with standard Cryptococcus locus identifiers and have incorporated them into FungiDB (www.fungidb.org). FungiDB is a panfungal genome database that collects gene information and functional data and provides search tools for 61 species of fungi and oomycetes. We applied these published names to a manually curated ortholog set of all Cryptococcus species currently in FungiDB, including Cryptococcus neoformans var. neoformans strains JEC21 and B-3501A, C. neoformans var. grubii strain H99, and Cryptococcus gattii strains R265 and WM276, and have written brief descriptions of their functions. We also compiled a protocol for gene naming that summarizes guidelines proposed by members of the Cryptococcus research community. The centralization of genomic and literature-based information for Cryptococcus at FungiDB will help researchers communicate about genes of interest, such as those related to virulence, and will further facilitate research on the pathogen.

The Aspergillus Genome Database: multispecies curation and incorporation of RNA-Seq data to improve structural gene annotations.

The Aspergillus Genome Database (AspGD; http://www.aspgd.org) is a freely available web-based resource that was designed for Aspergillus researchers and is also a valuable source of information for the entire fungal research community. In addition to being a repository and central point of access to genome, transcriptome and polymorphism data, AspGD hosts a comprehensive comparative genomics toolbox that facilitates the exploration of precomputed orthologs among the 20 currently available Aspergillus genomes. AspGD curators perform gene product annotation based on review of the literature for four key Aspergillus species: Aspergillus nidulans, Aspergillus oryzae, Aspergillus fumigatus and Aspergillus niger. We have iteratively improved the structural annotation of Aspergillus genomes through the analysis of publicly available transcription data, mostly expressed sequenced tags, as described in a previous NAR Database article (Arnaud et al. 2012). In this update, we report substantive structural annotation improvements for A. nidulans, A. oryzae and A. fumigatus genomes based on recently available RNA-Seq data. Over 26 000 loci were updated across these species; although those primarily comprise the addition and extension of untranslated regions (UTRs), the new analysis also enabled over 1000 modifications affecting the coding sequence of genes in each target genome.

The Candida Genome Database: the new homology information page highlights protein similarity and phylogeny.

The Candida Genome Database (CGD, http://www.candidagenome.org/) is a freely available online resource that provides gene, protein and sequence information for multiple Candida species, along with web-based tools for accessing, analyzing and exploring these data. The goal of CGD is to facilitate and accelerate research into Candida pathogenesis and biology. The CGD Web site is organized around Locus pages, which display information collected about individual genes. Locus pages have multiple tabs for accessing different types of information; the default Summary tab provides an overview of the gene name, aliases, phenotype and Gene Ontology curation, whereas other tabs display more in-depth information, including protein product details for coding genes, notes on changes to the sequence or structure of the gene and a comprehensive reference list. Here, in this update to previous NAR Database articles featuring CGD, we describe a new tab that we have added to the Locus page, entitled the Homology Information tab, which displays phylogeny and gene similarity information for each locus.

The reference genome sequence of Saccharomyces cerevisiae: then and now.

The genome of the budding yeast Saccharomyces cerevisiae was the first completely sequenced from a eukaryote. It was released in 1996 as the work of a worldwide effort of hundreds of researchers. In the time since, the yeast genome has been intensively studied by geneticists, molecular biologists, and computational scientists all over the world. Maintenance and annotation of the genome sequence have long been provided by the Saccharomyces Genome Database, one of the original model organism databases. To deepen our understanding of the eukaryotic genome, the S. cerevisiae strain S288C reference genome sequence was updated recently in its first major update since 1996. The new version, called "S288C 2010," was determined from a single yeast colony using modern sequencing technologies and serves as the anchor for further innovations in yeast genomic science.

Comprehensive annotation of secondary metabolite biosynthetic genes and gene clusters of Aspergillus nidulans, A. fumigatus, A. niger and A. oryzae.

BACKGROUND: Secondary metabolite production, a hallmark of filamentous fungi, is an expanding area of research for the Aspergilli. These compounds are potent chemicals, ranging from deadly toxins to therapeutic antibiotics to potential anti-cancer drugs. The genome sequences for multiple Aspergilli have been determined, and provide a wealth of predictive information about secondary metabolite production. Sequence analysis and gene overexpression strategies have enabled the discovery of novel secondary metabolites and the genes involved in their biosynthesis. The Aspergillus Genome Database (AspGD) provides a central repository for gene annotation and protein information for Aspergillus species. These annotations include Gene Ontology (GO) terms, phenotype data, gene names and descriptions and they are crucial for interpreting both small- and large-scale data and for aiding in the design of new experiments that further Aspergillus research. RESULTS: We have manually curated Biological Process GO annotations for all genes in AspGD with recorded functions in secondary metabolite production, adding new GO terms that specifically describe each secondary metabolite. We then leveraged these new annotations to predict roles in secondary metabolism for genes lacking experimental characterization. As a starting point for manually annotating Aspergillus secondary metabolite gene clusters, we used antiSMASH (antibiotics and Secondary Metabolite Analysis SHell) and SMURF (Secondary Metabolite Unknown Regions Finder) algorithms to identify potential clusters in A. nidulans, A. fumigatus, A. niger and A. oryzae, which we subsequently refined through manual curation. CONCLUSIONS: This set of 266 manually curated secondary metabolite gene clusters will facilitate the investigation of novel Aspergillus secondary metabolites.

Improved gene ontology annotation for biofilm formation, filamentous growth, and phenotypic switching in Candida albicans.

The opportunistic fungal pathogen Candida albicans is a significant medical threat, especially for immunocompromised patients. Experimental research has focused on specific areas of C. albicans biology, with the goal of understanding the multiple factors that contribute to its pathogenic potential. Some of these factors include cell adhesion, invasive or filamentous growth, and the formation of drug-resistant biofilms. The Gene Ontology (GO) (www.geneontology.org) is a standardized vocabulary that the Candida Genome Database (CGD) (www.candidagenome.org) and other groups use to describe the functions of gene products. To improve the breadth and accuracy of pathogenicity-related gene product descriptions and to facilitate the description of as yet uncharacterized but potentially pathogenicity-related genes in Candida species, CGD undertook a three-part project: first, the addition of terms to the biological process branch of the GO to improve the description of fungus-related processes; second, manual recuration of gene product annotations in CGD to use the improved GO vocabulary; and third, computational ortholog-based transfer of GO annotations from experimentally characterized gene products, using these new terms, to uncharacterized orthologs in other Candida species. Through genome annotation and analysis, we identified candidate pathogenicity genes in seven non-C. albicans Candida species and in one additional C. albicans strain, WO-1. We also defined a set of C. albicans genes at the intersection of biofilm formation, filamentous growth, pathogenesis, and phenotypic switching of this opportunistic fungal pathogen, which provides a compelling list of candidates for further experimentation.

The Aspergillus Genome Database (AspGD): recent developments in comprehensive multispecies curation, comparative genomics and community resources.

The Aspergillus Genome Database (AspGD; http://www.aspgd.org) is a freely available, web-based resource for researchers studying fungi of the genus Aspergillus, which includes organisms of clinical, agricultural and industrial importance. AspGD curators have now completed comprehensive review of the entire published literature about Aspergillus nidulans and Aspergillus fumigatus, and this annotation is provided with streamlined, ortholog-based navigation of the multispecies information. AspGD facilitates comparative genomics by providing a full-featured genomics viewer, as well as matched and standardized sets of genomic information for the sequenced aspergilli. AspGD also provides resources to foster interaction and dissemination of community information and resources. We welcome and encourage feedback at aspergillus-curator@lists.stanford.edu.