WormBase: It’s not just for C. elegans anymore

WormBase — wormbase.org — is the central data repository for Caenorhabditis elegans and related nematodes.

C. elegans is a well-known system for studying problems in developmental biology, the benefits of which I will quickly rehash here. Its rapid generation time from fertilized egg to gravid adult (3.5 days) and small size (1mM) permit 1000’s of animals to be grown on a single plate in short order. As a self-fertilizing hermaphrodite, isogenic populations can be generated from a single animal. And the presence of occasional males permits standard crosses to create different genetic backgrounds. Moreover, the complete (and invariant from worm to worm) developmental lineage and neuronal connectivity are known. Thus C. elegans is an ideal system in which to conduct genetic screens looking for mutations that specifically disrupt developmental processes. Comparison to the baseline lineage and neuronal connectivity can provide quick insight into gene function, and standard genetic techniques can be used to identify interacting or regulatory genes.

WormBase supports the use of C. elegans as a model system by collecting and annotating experimental data from the published literature. By placing these data in a rich intellectual framework, WormBase facilitates further discovery that may not be readily apparent from studying the data in isolation. For example, WormBase gene summary pages contain manually curated, concise descriptions of the gene, which report gene function (summarized from null phenotype analysis when available), expression patterns, ortholog assignments,  and link to OMIM (Online Mendelian Inheritance of Man) if predicted orthologs are associated with genes involved in human disease. These pages also display phenotype data based on both mutant analysis and RNAi knockdown experiments. Further, these gene pages display the results of in-house homolog analysis using a number of different analysis tools: BLASTP, Inparanoid 7, Compara and TreeFam. Finally, WormBase is an active member of the GO Consortium and has placed a consistent effort on annotating genes with GO biological process and molecular function terms, as well as placing gene function in the context of a cell component when warranted.  These GO assignments together with the rest of the curation efforts and services WormBase provides, put C. elegans research in a larger biological scope for the understanding of biological processes and create a ready means for our community to access it.

Cross species analysis is also supported by WormBase. Currently, WormBase contains the completed genomic sequence of C. elegans and has recently added  five genomes of related sister species, bringing the total to ten nematode genomes (five sister Caenorhabditis and five distantly related nematode genomes).  The C. elegans genome can be viewed and navigated using the latest GBrowse genome viewer developed by Lincoln Stein.  This genome viewer allows direct comparisons between C. elegans predicted gene structures to  some of these different species in its synteny viewer.

What if your model system of choice isn’t C. elegans? First, don’t despair; it’s never too late to switch organisms. We jest. Still, WormBase has great utility for users working in other model systems. First, you can bring the extensive experimental evidence available in C. elegans to bear on research problems outside of the system. For example, you can search WormBase using Uniprot identifiers to quickly identify orthologs. You can also navigate through the complete cell pedigree using an Anatomy Ontology browser, or explore neuronal connectivity of C. elegans through the direct links to NeuralNet.  Ontology browsers are also provided for GO terms and phenotypes, which should provide you with a wealth of information and context for your gene of interest.

Recently, WormBase celebrated its 10th anniversary, a heady milestone and veritable eternity in internet time. WormBase has come a long way from our initial days of housing mainly genomic data for a single nematode to now hosting pages upon pages of extracted biological descriptions of various aspects of those genes sequenced so long ago.  And now that we have many more genomes to deal with, the fun continues in a new direction to build a richer repository for scientists to use to uncover the mechanisms of development.

I’d also like to take this opportunity to point out related projects that may be of interest. As mentioned above, the Caenorhabditis Genetics Center houses, catalogs, and provides strains to the worm community.  Many knockout and allele generating consortiums are willing suppliers of strains with a lesion in your favorite worm gene. These include the C. elegans Gene Knockout Consortium,  the National Bioresource Project of Japan, and  NemaGENETAG. WormAtlas along with  NeuralNet is another very important web resource that we link to for our community to get an  in-depth view of the anatomy and wiring of the worm.  And finally, WormBook,  a companion website to WormBase, is a peer-reviewed reference guide to the genetical analysis and experimental methods used for studying C. elegans, as well as providing copious chapters reviewing all aspects of the biology of C. elegans and related species.

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