WormBase
Encyclopedia
WormBase is an online bioinformatics
database
of the biology and genome of the model organism
Caenorhabditis elegans
and related nematodes.
It is used by the C. elegans research community both as an information resource and as a mode to publish and distribute their results. The database is constantly updated and new versions are released on a monthly basis.
WormBase is one of the organizations participating in the Generic Model Organism Database
(GMOD) project.
In addition, WormBase contains an up-to-date searchable bibliography of C. elegans research and is linked to the WormBook
project.
The changes in the genomic sequence pose difficulties when comparing chromosomal coordinates of data derived from different releases of WormBase. To aid these comparisons, a coordinate re-mapping program and data are available from:
http://wiki.wormbase.org/index.php/Converting_Coordinates_between_releases
The gene models of C. elegans, C. briggsae, C. remanei, and C. brenneri genes are manually curated. The majority of gene structure changes have been based on transcript data from large scale projects such as Yuji Kohara’s EST libraries, Mark Vidal’s Orfeome project (worfdb.dfci.harvard.edu/) Waterston and Hillier’s Illumina data and Makedonka Mitreva’s 454 data. However, other data types (e.g. protein alignments, ab initio prediction programs, trans-splice leader sites, poly-A signals and addition sites, SAGE and TEC-RED transcript tags, mass-spectroscopic peptides, and conserved protein domains) are useful in refining the structures, especially where expression is low and so transcripts are not sufficiently available. When genes are conserved between the available nematode species, comparative analysis can also be very informative.
WormBase encourages researchers to inform them via the help-desk if they have evidence for an incorrect gene structure. Any cDNA or mRNA sequence evidence for the change should be submitted to EMBL/GenBank/DDBJ; this helps in the confirmation and evidence for the gene model as WormBase routinely retrieve sequence data from these public databases. This also makes the data public, allowing appropriate reference and acknowledgement to the researchers.
When any change is made to a CDS (or Pseudogene), the old gene model is preserved as a ‘history’ object. This will have a suffix name like: “AC3.5:wp119”, where ‘AC3.5’ is the name of the CDS and the ‘119’ refers to the database release in which the change was made. The reason for the change and the evidence for the change are added to the annotation of the CDS – these can be seen in the Visible/Remark section of the CDS’s ‘Tree Display’ section on the WormBase web site.
There are a few exceptions to this format, like the genes cln-3.1, cln-3.2, and cln-3.3 which all are equally similar to the human gene CLN3.
Gene GCG names for non-elegans species in WormBase have the 3-letter species code prepended, like Cre-acl-5, Cbr-acl-5, Cbn-acl-5.
A gene can be a Pseudogene, or can express one or more non-coding RNA genes (ncRNA) or protein-coding sequences (CDS).
CDSs have a Sequence Name that is derived from the same Sequence Name as their parent Gene object, so the gene ‘F38H4.7’ has a CDS called ‘F38H4.7’. The CDS specifies coding exons in the gene from the START (Methionine) codon up to (and including) the STOP codon.
Any gene can code for multiple proteins as a result of alternative splicing. These isoforms have a name that is formed from the Sequence Name of the gene with a unique letter appended. In the case of the gene bli-4 there are 6 known CDS isoforms, called K04F10.4a, K04F10.4b, K04F10.4c, K04F10.4d, K04F10.4e and K04F10.4f.
It is common to refer to isoforms in the literature using the CGC gene family name with a letter appended, for example pha-4a, however this has no meaning within the WormBase database and searches for pha-4a in WormBase will not return anything. The correct name of this isoform is either the CDS/Transcript name: F38A6.1a, or even better, the Protein name: WP:CE15998.
Gene transcripts are named after the Sequence Name of the CDS used to create them, for example, F38H4.7 or K04F10.4a.
However if there is alternative splicing in the UTRs, which would not change the protein sequence, the alternatively-spliced transcripts are named with a digit appended, for example: K04F10.4a.1 and K04F10.4a.2. If there are no isoforms of the coding gene, for example AC3.5, but there is alternative splicing in the UTRs, there will be multiple transcripts named AC3.5.1 and AC3.5.2, etc. If there are no alternate UTR transcripts the single coding_transcript is named the same as the CDS and does not have the .1 appended, as in the case of K04F10.4f.
There is also one scRNA gene.
It is possible for two CDS sequences from separate genes, within a species, to be identical and so it is possible to have identical proteins coded for by separate genes. When this happens, a single, unique identifying name is used for the protein even though it is produced by two genes.
, Wellcome Trust Sanger Institute, Ontario Institute for Cancer Research
, Washington University in St. Louis
, and the California Institute of Technology
. It is supported by the grant P41-HG02223 from the National Institutes of Health
and the grant G0701197 from the British Medical Research Council
.
Bioinformatics
Bioinformatics is the application of computer science and information technology to the field of biology and medicine. Bioinformatics deals with algorithms, databases and information systems, web technologies, artificial intelligence and soft computing, information and computation theory, software...
database
Database
A database is an organized collection of data for one or more purposes, usually in digital form. The data are typically organized to model relevant aspects of reality , in a way that supports processes requiring this information...
of the biology and genome of the model organism
Model organism
A model organism is a non-human species that is extensively studied to understand particular biological phenomena, with the expectation that discoveries made in the organism model will provide insight into the workings of other organisms. Model organisms are in vivo models and are widely used to...
Caenorhabditis elegans
Caenorhabditis elegans
Caenorhabditis elegans is a free-living, transparent nematode , about 1 mm in length, which lives in temperate soil environments. Research into the molecular and developmental biology of C. elegans was begun in 1974 by Sydney Brenner and it has since been used extensively as a model...
and related nematodes.
It is used by the C. elegans research community both as an information resource and as a mode to publish and distribute their results. The database is constantly updated and new versions are released on a monthly basis.
WormBase is one of the organizations participating in the Generic Model Organism Database
Generic Model Organism Database
The Generic Model Organism Database Project began as an effort to create reusable software tools for developing Model Organism Databases . MODs describe genome and other information about important experimental organisms in the life sciences...
(GMOD) project.
Contents
WormBase comprises the following main data sets:- The annotated genomes of Caenorhabditis elegansCaenorhabditis elegansCaenorhabditis elegans is a free-living, transparent nematode , about 1 mm in length, which lives in temperate soil environments. Research into the molecular and developmental biology of C. elegans was begun in 1974 by Sydney Brenner and it has since been used extensively as a model...
, Caenorhabditis briggsaeCaenorhabditis briggsaeCaenorhabditis briggsae is a small nematode, closely related to Caenorhabditis elegans. The differences between the two species are subtle. The male tail in C. briggsae has a slightly different morphology than C. elegans. Other differences include changes in vulval precursor competence and the...
, Caenorhabditis remaneiCaenorhabditis remaneiCaenorhabditis remanei is a species of nematode that has been found in North America and Europe, and likely lives throughout the temperate world. Several strains have been developed in the laboratory. -Habitat:...
, Caenorhabditis brenneriCaenorhabditis brenneriCaenorhabditis brenneri is a small nematode, closely related to the model organism Caenorhabditis elegans and to other species in the same genus. Its genome is being sequenced by Washington University in St. Louis Genome Sequencing Center . This species has previously been referred to as C. sp 4...
, Caenorhabditis cangaria, Pristionchus pacificus, Haemonchus contortusHaemonchus contortusHaemonchus contortus, also known as red stomach worm, wire worm or Barber's pole worm, is very common parasite and one the most pathogenic nematode of ruminants. Adult worms are attached to abomasal mucosa and feed on the blood...
, Meloidogyne hapla, Meloidogyne incognitaMeloidogyne incognitaThe Meloidogyne incognita is a nematode, a type of roundworm, in the family Heteroderidae. It is an important plant parasite classified in parasitology as a root-knot nematode, as it prefers to attack the root of its host plant....
, and Brugia malayiBrugia malayiBrugia malayi is a nematode , one of the three causative agents of lymphatic filariasis in humans. Lymphatic filariasis, also known as elephantiasis, is a condition characterized by swelling of the lower limbs. The two other filarial causes of lymphatic filariasis are Wuchereria bancrofti and...
; - Hand-curated annotations describing the function of ~20,500 C. elegans protein-coding genes and ~16,000 C. elegans non-coding genes;
- Gene families;
- Orthologies;
- Genomic transcription factor binding sites
- Comprehensive information on mutant alleles and their phenotypes;
- Whole-genome RNAiRNAIRNAI is a non-coding RNA that is an antisense repressor of the replication of some E. coli plasmids, including ColE1. Plasmid replication is usually initiated by RNAII, which acts as a primer by binding to its template DNA. The complementary RNAI binds RNAII prohibiting it from its initiation role...
(RNA interference) screens; - Genetic maps, markers and polymorphisms;
- The C. elegans physical map;
- Gene expression profiles (stage, tissue and cell) from microarrays, SAGE analysis and GFP promoter fusions;
- The complete cell lineage of the worm;
- The wiring diagram of the worm nervous system;
- Protein-protein interaction InteractomeInteractomeInteractome is defined as the whole set of molecular interactions in cells. It is usually displayed as a directed graph. Molecular interactions can occur between molecules belonging to different biochemical families and also within a given family...
data; - Genetic regulatory relationships;
- Details of intra- and inter-specific sequence homologiesHomology (biology)Homology forms the basis of organization for comparative biology. In 1843, Richard Owen defined homology as "the same organ in different animals under every variety of form and function". Organs as different as a bat's wing, a seal's flipper, a cat's paw and a human hand have a common underlying...
(with links to other model organism databases).
In addition, WormBase contains an up-to-date searchable bibliography of C. elegans research and is linked to the WormBook
WormBook
WormBook is an open access, comprehensive collection of original, peer-reviewed chapters covering topics related to the biology of Caenorhabditis elegans . WormBook also includes WormMethods, an up-to-date collection of methods and protocols for C. elegans researchers.WormBook is the online text...
project.
Tools
WormBase offers many ways of searching and retrieving data from the database:- WormMart - a tool for retrieving varied information on many genes (or the sequences of those genes). This is the WormBase implementation of BioMart.
- Genome Browser - browse the genes of C. elegans (and other species) in their genomic context
- TextPresso - a search tool that queries published C. elegans literature (including meeting abstracts)
Sequence Curation
Sequence curation at WormBase refers to the maintenance and annotation of the primary genomic sequence and a consensus gene set.Genome Sequence
Even though the C. elegans genome sequence is the most accurate and complete eukaryotic genome sequence, it has continually needed refinement as new evidence has been created. Many of these changes were single nucleotide insertions or deletions, however several large mis-assemblies have been uncovered. For example, in 2005 a 39 kb cosmid had to be inverted. Other improvements have come from comparing genomic DNA to cDNA sequences and analysis of RNASeq high-throughput data. When differences between the genomic sequence and transcripts are identified, re-analysis of the original genomic data often leads to modifications of the genomic sequence.The changes in the genomic sequence pose difficulties when comparing chromosomal coordinates of data derived from different releases of WormBase. To aid these comparisons, a coordinate re-mapping program and data are available from:
http://wiki.wormbase.org/index.php/Converting_Coordinates_between_releases
Gene structure models
All the gene-sets of the WormBase species were initially generated by gene prediction programs. Gene prediction programs give a reasonable set of gene structures, but the best of them only predict about 80% of the complete gene structures correctly. They have difficulty predicting genes with unusual structures, as well as those with a weak translation start signal, weak splice sites or single exon genes. They can incorrectly predict a coding gene model where the gene is a pseudogene and they predict the isoforms of a gene poorly, if at all.The gene models of C. elegans, C. briggsae, C. remanei, and C. brenneri genes are manually curated. The majority of gene structure changes have been based on transcript data from large scale projects such as Yuji Kohara’s EST libraries, Mark Vidal’s Orfeome project (worfdb.dfci.harvard.edu/) Waterston and Hillier’s Illumina data and Makedonka Mitreva’s 454 data. However, other data types (e.g. protein alignments, ab initio prediction programs, trans-splice leader sites, poly-A signals and addition sites, SAGE and TEC-RED transcript tags, mass-spectroscopic peptides, and conserved protein domains) are useful in refining the structures, especially where expression is low and so transcripts are not sufficiently available. When genes are conserved between the available nematode species, comparative analysis can also be very informative.
WormBase encourages researchers to inform them via the help-desk if they have evidence for an incorrect gene structure. Any cDNA or mRNA sequence evidence for the change should be submitted to EMBL/GenBank/DDBJ; this helps in the confirmation and evidence for the gene model as WormBase routinely retrieve sequence data from these public databases. This also makes the data public, allowing appropriate reference and acknowledgement to the researchers.
When any change is made to a CDS (or Pseudogene), the old gene model is preserved as a ‘history’ object. This will have a suffix name like: “AC3.5:wp119”, where ‘AC3.5’ is the name of the CDS and the ‘119’ refers to the database release in which the change was made. The reason for the change and the evidence for the change are added to the annotation of the CDS – these can be seen in the Visible/Remark section of the CDS’s ‘Tree Display’ section on the WormBase web site.
Genes
In WormBase, a Gene is a region that is expressed or a region that has been expressed and is now a Pseudogene. Genes have unique identifiers like ‘WBGene00006415’. All C. elegans WormBase genes also have a Sequence Name, which is derived from the cosmid, fosmid or YAC clone on which they reside, for instance F38H4.7, indicating it is on the cosmid ‘F38H4’, and there are at least 6 other genes on that cosmid. If a gene produces a protein that can be classified as a member of a family, the gene may also be assigned a CGC name like tag-30 indicating that this is the 30th member of the tag gene family. Assignment of gene family names is controlled by WormBase and requests for names should be made, before publication, via the form at: http://tazendra.caltech.edu/~azurebrd/cgi-bin/forms/gene_name.cgiThere are a few exceptions to this format, like the genes cln-3.1, cln-3.2, and cln-3.3 which all are equally similar to the human gene CLN3.
Gene GCG names for non-elegans species in WormBase have the 3-letter species code prepended, like Cre-acl-5, Cbr-acl-5, Cbn-acl-5.
A gene can be a Pseudogene, or can express one or more non-coding RNA genes (ncRNA) or protein-coding sequences (CDS).
Pseudogenes
Pseudogenes are genes that do not produce a reasonable, functional transcript. They may be pseudogenes of coding genes or of non-coding RNA and may be whole or fragments of a gene and may or may not express a transcript. The boundary between what is considered a reasonable coding transcript is sometimes subjective as, in the absence of other evidence, the use of weak splice sites or short exons can often produce a putative, though unsatisfactory, model of a CDS. Pseudogenes and genes with a problematic structure are constantly under review in WormBase and new evidence is used to try to resolve their status.CDSs
Coding Sequences (CDSs) are the only part of a Gene's structure that is manually curated in WormBase. The structure of the Gene and its transcripts are derived from the structure of their CDSs.CDSs have a Sequence Name that is derived from the same Sequence Name as their parent Gene object, so the gene ‘F38H4.7’ has a CDS called ‘F38H4.7’. The CDS specifies coding exons in the gene from the START (Methionine) codon up to (and including) the STOP codon.
Any gene can code for multiple proteins as a result of alternative splicing. These isoforms have a name that is formed from the Sequence Name of the gene with a unique letter appended. In the case of the gene bli-4 there are 6 known CDS isoforms, called K04F10.4a, K04F10.4b, K04F10.4c, K04F10.4d, K04F10.4e and K04F10.4f.
It is common to refer to isoforms in the literature using the CGC gene family name with a letter appended, for example pha-4a, however this has no meaning within the WormBase database and searches for pha-4a in WormBase will not return anything. The correct name of this isoform is either the CDS/Transcript name: F38A6.1a, or even better, the Protein name: WP:CE15998.
Gene transcripts
The transcripts of a gene in WormBase are automatically derived by mapping any available cDNA or mRNA alignments onto the CDS model. These gene transcripts will therefore often include the UTR exons surrounding the CDS. If there are no available cDNA or mRNA transcripts, then the gene transcripts will have exactly the same structure as the CDS that they are modelled on.Gene transcripts are named after the Sequence Name of the CDS used to create them, for example, F38H4.7 or K04F10.4a.
However if there is alternative splicing in the UTRs, which would not change the protein sequence, the alternatively-spliced transcripts are named with a digit appended, for example: K04F10.4a.1 and K04F10.4a.2. If there are no isoforms of the coding gene, for example AC3.5, but there is alternative splicing in the UTRs, there will be multiple transcripts named AC3.5.1 and AC3.5.2, etc. If there are no alternate UTR transcripts the single coding_transcript is named the same as the CDS and does not have the .1 appended, as in the case of K04F10.4f.
Operons
Groups of genes which are co-transcribed as operons are curated as Operon objects. These have names like CEOP5460 and are manually curated using evidence from the SL2 trans-spliced leader sequence sites.Non-coding RNA genes
There are several classes of non-coding RNA gene classes in WormBase:- tRNA genes are predicted by the program ‘tRNAscan-SE’.
- rRNA genes are predicted by homology with other species.
- snRNA genes are mainly imported from Rfam.
- piRNA genes are from an analysis of the characteristic motif in these genes.
- miRNA genes have mainly been imported from mirBASE. They have the primary transcript and the mature transcript marked up. The primary transcript will have a Sequence name like W09G3.10 and the mature transcript will have a letter added to this name like W09G3.10a (and if there are alternative mature transcripts, W09G3.10b, etc.).
- snoRNA genes are mainly imported from Rfam or from papers.
- ncRNA genes that have no obvious other function but which are obviously not protein-coding and are not pseudogenes are curated. Many of these have conserved homology with genes in other species. A few of these are expressed on the reverse sense to protein-coding genes.
There is also one scRNA gene.
Transposons
Transposons are not classed as genes and so do not have a parent gene object. Their structure is curated as a Transposon_CDS object with a name like C29E6.6.Other Species
The non-elegans species in WormBase have genomes that have been assembled from sequencing technologies that do not involve sequencing cosmids or YACs. These species therefore do not have sequence names for CDSs and gene transcripts that are based on cosmid names. Instead they have unique alphanumeric identifiers constructed like the names in the table below.| Species | Example Gene name |
|---|---|
| C. briggsae | CBG00001 |
| C. remanei | CRE00001 |
| C. brenneri | CBN00001 |
| C. japonica | CJA00001 |
| Pristionchus pacificus | PPA00001 |
Proteins
The protein products of gene are created by translating the CDS sequences. Each unique protein sequence is given a unique identifying name like WP:CE40440. Examples of the protein identifier names for each species in WormBase is given in the table, below.| Species | Example Protein name |
|---|---|
| C. elegans | WP:CE00001 |
| C. briggsae | BP:CBP00001 |
| C. remanei | RP:RP00001 |
| C. brenneri | CN:CN00001 |
| C. japonica | JA:JA00001 |
| Pristionchus pacificus | PP:PP00001 |
| Heterorhabditis bacteriophora | HB:HB00001 |
| Brugia malayi | BM:BM00001 |
| Meloidogyne hapla | MH:MH00001 |
| Meloidogyne incognita | MI:MI00001 |
| Haemonchus contortus | HC:HC00001 |
It is possible for two CDS sequences from separate genes, within a species, to be identical and so it is possible to have identical proteins coded for by separate genes. When this happens, a single, unique identifying name is used for the protein even though it is produced by two genes.
WormBase Management
WormBase is a collaboration among the European Bioinformatics InstituteEuropean Bioinformatics Institute
The European Bioinformatics Institute is a centre for research and services in bioinformatics, and is part of European Molecular Biology Laboratory...
, Wellcome Trust Sanger Institute, Ontario Institute for Cancer Research
Ontario Institute for Cancer Research
The Ontario Institute for Cancer Research is a not-for-profit organization based in Toronto, Ontario, Canada that focuses on the prevention, early detection, diagnosis and treatment of cancer. OICR intends to make Ontario more effective in knowledge transfer and commercialization while maximizing...
, Washington University in St. Louis
Washington University in St. Louis
Washington University in St. Louis is a private research university located in suburban St. Louis, Missouri. Founded in 1853, and named for George Washington, the university has students and faculty from all fifty U.S. states and more than 110 nations...
, and the California Institute of Technology
California Institute of Technology
The California Institute of Technology is a private research university located in Pasadena, California, United States. Caltech has six academic divisions with strong emphases on science and engineering...
. It is supported by the grant P41-HG02223 from the National Institutes of Health
National Institutes of Health
The National Institutes of Health are an agency of the United States Department of Health and Human Services and are the primary agency of the United States government responsible for biomedical and health-related research. Its science and engineering counterpart is the National Science Foundation...
and the grant G0701197 from the British Medical Research Council
Medical Research Council (UK)
The Medical Research Council is a publicly-funded agency responsible for co-ordinating and funding medical research in the United Kingdom. It is one of seven Research Councils in the UK and is answerable to, although politically independent from, the Department for Business, Innovation and Skills...
.
External links
- WormBase
- The WormBook website, the online textbook companion to WormBase.
- Textpresso, search engine for C. elegans and other biological literature.
- WormBase Wiki
- Release notes, details of the latest WormBase release
- WormBase: better software, richer content Nucleic Acids Research article describing WormBase (2006).