The consensus coding sequence (CCDS) project: Identifying a common protein-coding gene set for the human and mouse genomes

Abstract

Effective use of the human and mouse genomes requires reliable identification of genes and their products. Although multiple public resources provide annotation, different methods are used that can result in similar but not identical representation of genes, transcripts, and proteins. The collaborative consensus coding sequence (CCDS) project tracks identical protein annotations on the reference mouse and human genomes with a stable identifier (CCDS ID), and ensures that they are consistently represented on the NCBI, Ensembl, and UCSC Genome Browsers. Importantly, the project coordinates on manually reviewing inconsistent protein annotations between sites, as well as annotations for which new evidence suggests a revision is needed, to progressively converge on a complete protein-coding set for the human and mouse reference genomes, while maintaining a high standard of reliability and biological accuracy. To date, the project has identified 20,159 human and 17,707 mouse consensus coding regions from 17,052 human and 16,893 mouse genes. Three evaluation methods indicate that the entries in the CCDS set are highly likely to represent real proteins, more so than annotations from contributing groups not included in CCDS. The CCDS database thus centralizes the function of identifying well-supported, identically-annotated, protein-coding regions.

Figure 1.

The percentage of mouse CCDS proteins that are found in any HomoloGene cluster versus those in a cluster that also contains a human CCDS protein (first two bars, respectively). For the latter category, results are further categorized based on protein length differences for the human and mouse homologous proteins.

Figure 2.

The percentage of human and mouse genes, with associated CCDS IDs for one or more proteins that are identical (C), similar (B) , or unique (A) when compared to SWISS-PROT records and to SWISS-PROT isoforms that were extracted from record annotation (see Methods). (D) The total number of high-quality matches.

Figure 3.

Cumulative distributions of RFC scores for human (A) and mouse (B). These graphs compare the RFC scores for CCDS loci with those of RefSeq and Ensembl loci that do not contain a CCDS protein, as well as a control data set for human. Since the controls were designed to have a similar alignment coverage to well-known genes, loci in other gene sets with less alignment coverage will score less than the controls.

Figure 4.

Detailed CCDS ID report page for a MXI1 protein. The CCDS report page presents three tables of information followed by nucleotide and protein sequences for the annotated CDS. The first table summarizes the status for the specified CCDS ID. Colored icons provide links to related resources, to a history report (orange H icon), or to re-query the CCDS database with a different type of identifier. (Red G icon re-queries the CCDS database by GeneID to return all CCDS IDs available for a gene.) A Public Note is provided for a subset of curated records to explain the nature of, and/or the reason for, an update or withdrawal. The sequence identifiers table reports sequences tracked as members of the CCDS ID. A checkmark in the first column (Original) identifies sequence identifiers represented on the annotated genome and included in the analyzed input data sets, and a checkmark in the second column (Current) identifies those that are considered current members (see Supplemental Fig. 2) The Chromosome Locations table reports the genomic coordinates of each exon of the CDS with links to view the annotation in different browsers—the violet icons (N) NCBI; (U) UCSC; (E) Ensembl; and (V) Vega. The nucleotide sequence of the CDS, derived from the genome sequence using the reported exon.