Genomic sequencing has made it clear that a large fraction of the genes specifying the core biological functions are shared by all eukaryotes. Knowledge of the biological role of such shared proteins in one organism can often be transferred to other organisms. The goal of the Gene Ontology Consortium is to produce a dynamic, controlled vocabulary that can be applied to all eukaryotes even as knowledge of gene and protein roles in cells is accumulating and changing. To this end, three independent ontologies accessible on the World-Wide Web (http://www.geneontology.org) are being constructed: biological process, molecular function and cellular component.The accelerating availability of molecular sequences, particularly the sequences of entire genomes, has transformed both the theory and practice of experimental biology. Where once biochemists characterized proteins by their diverse activities and abundances, and geneticists characterized genes by the phenotypes of their mutations, all biologists now acknowledge that there is likely to be a single limited universe of genes and proteins, many of which are conserved in most or all living cells. This recognition has fuelled a grand unification of biology; the information about the shared genes and proteins contributes to our understanding of all the diverse organisms that share them. Knowledge of the biological role of such a shared protein in one organism can certainly illuminate, and often provide strong inference of, its role in other organisms.Progress in the way that biologists describe and conceptualize the shared biological elements has not kept pace with sequencing. For the most part, the current systems of nomenclature for genes and their products remain divergent even when the experts appreciate the underlying similarities. Interoperability of genomic databases is limited by this lack of progress, and it is this major obstacle that the Gene Ontology (GO) Consortium was formed to address.

The fly Drosophila melanogaster is one of the most intensively studied organisms in biology and serves as a model system for the investigation of many developmental and cellular processes common to higher eukaryotes, including humans. We have determined the nucleotide sequence of nearly all of the ∼120-megabase euchromatic portion of the Drosophila genome using a whole-genome shotgun sequencing strategy supported by extensive clone-based sequence and a high-quality bacterial artificial chromosome physical map. Efforts are under way to close the remaining gaps; however, the sequence is of sufficient accuracy and contiguity to be declared substantially complete and to support an initial analysis of genome structure and preliminary gene annotation and interpretation. The genome encodes ∼13,600 genes, somewhat fewer than the smaller Caenorhabditis elegans genome, but with comparable functional diversity.

As the sequencing of healthy and disease genomes becomes more commonplace, detailed annotation provides interpretation for individual variation responsible for normal and disease phenotypes. Current approaches focus on direct changes in protein coding genes, particularly nonsynonymous mutations that directly affect the gene product. However, most individual variation occurs outside of genes and, indeed, most markers generated from genome-wide association studies (GWAS) identify variants outside of coding segments. Identification of potential regulatory changes that perturb these sites will lead to a better localization of truly functional variants and interpretation of their effects. We have developed a novel approach and database, RegulomeDB, which guides interpretation of regulatory variants in the human genome. RegulomeDB includes high-throughput, experimental data sets from ENCODE and other sources, as well as computational predictions and manual annotations to identify putative regulatory potential and identify functional variants. These data sources are combined into a powerful tool that scores variants to help separate functional variants from a large pool and provides a small set of putative sites with testable hypotheses as to their function. We demonstrate the applicability of this tool to the annotation of noncoding variants from 69 full sequenced genomes as well as that of a personal genome, where thousands of functionally associated variants were identified. Moreover, we demonstrate a GWAS where the database is able to quickly identify the known associated functional variant and provide a hypothesis as to its function. Overall, we expect this approach and resource to be valuable for the annotation of human genome sequences. [Supplemental material is available for this article.]The increasing number of sequenced human genomes is providing a catalog of the large number of individual variations present in the human genome (The International HapMap Consortium 2005; The 1000 Genomes Project Consortium 2010). Many of these variants are expected to be responsible for normal and disease phenotypes. Similarly, large, genome-wide association studies (GWAS) continue to map diseases to associated genomic regions from large cohorts of individuals (Hindorff et al. 2012). Initial interpretation of results generated by both of these approaches has been limited to DNA regions that cause disruption of gene function through coding sequence changes typically identified using an application such as PolyPhen-2 (Adzhubei et al. 2010). However, ;95% of known variants within sequenced genomes and 88% of those variants from GWAS studies fall outside of coding regions and have been difficult to interpret ).Both large consortia and individual labs are generating a significant amount of regulatory information that is providing a better interpretation of the noncoding portions of the genome. The ENCODE Project, in particular, has mapped open chromatin and protein binding regions for large numbers of factors across many cell type...

The Encyclopedia of DNA Elements (ENCODE) Data Coordinating Center has developed the ENCODE Portal database and website as the source for the data and metadata generated by the ENCODE Consortium. Two principles have motivated the design. First, experimental protocols, analytical procedures and the data themselves should be made publicly accessible through a coherent, web-based search and download interface. Second, the same interface should serve carefully curated metadata that record the provenance of the data and justify its interpretation in biological terms. Since its initial release in 2013 and in response to recommendations from consortium members and the wider community of scientists who use the Portal to access ENCODE data, the Portal has been regularly updated to better reflect these design principles. Here we report on these updates, including results from new experiments, uniformly-processed data from other projects, new visualization tools and more comprehensive metadata to describe experiments and analyses. Additionally, the Portal is now home to meta(data) from related projects including Genomics of Gene Regulation, Roadmap Epigenome Project, Model organism ENCODE (modENCODE) and modERN. The Portal now makes available over 13000 datasets and their accompanying metadata and can be accessed at: https://www.encodeproject.org/.

The Saccharomyces Genome Database (SGD, http://www.yeastgenome.org) is the community resource for the budding yeast Saccharomyces cerevisiae. The SGD project provides the highest-quality manually curated information from peer-reviewed literature. The experimental results reported in the literature are extracted and integrated within a well-developed database. These data are combined with quality high-throughput results and provided through Locus Summary pages, a powerful query engine and rich genome browser. The acquisition, integration and retrieval of these data allow SGD to facilitate experimental design and analysis by providing an encyclopedia of the yeast genome, its chromosomal features, their functions and interactions. Public access to these data is provided to researchers and educators via web pages designed for optimal ease of use.