Chris Mungall

Assessing the impact of comparative genomic sequence data on the functional annotation of the Drosophila genome

BackgroundIt is widely accepted that comparative sequence data can aid the functional annotation of genome sequences; however, the most informative species and features of genome evolution for comparison remain to be determined.ResultsWe analyzed conservation in eight genomic regions (apterous, even-skipped, fushi tarazu, twist, and Rhodopsins 1, 2, 3 and 4) from four Drosophila species (D. erecta, D. pseudoobscura, D. willistoni, and D. littoralis) covering more than 500 kb of the D. melanogaster genome. All D. melanogaster genes (and 78-82% of coding exons) identified in divergent species such as D. pseudoobscura show evidence of functional constraint. Addition of a third species can reveal functional constraint in otherwise non-significant pairwise exon comparisons. Microsynteny is largely conserved, with rearrangement breakpoints, novel transposable element insertions, and gene transpositions occurring in similar numbers. Rates of amino-acid substitution are higher in uncharacterized genes relative to genes that have previously been studied. Conserved non-coding sequences (CNCSs) tend to be spatially clustered with conserved spacing between CNCSs, and clusters of CNCSs can be used to predict enhancer sequences.ConclusionsOur results provide the basis for choosing species whose genome sequences would be most useful in aiding the functional annotation of coding and cis-regulatory sequences in Drosophila. Furthermore, this work shows how decoding the spatial organization of conserved sequences, such as the clustering of CNCSs, can complement efforts to annotate eukaryotic genomes on the basis of sequence conservation alone.

Annotation of the Drosophila melanogastereuchromatic genome: a systematic review

BackgroundThe recent completion of the Drosophila melanogaster genomic sequence to high quality and the availability of a greatly expanded set of Drosophila cDNA sequences, aligning to 78% of the predicted euchromatic genes, afforded FlyBase the opportunity to significantly improve genomic annotations. We made the annotation process more rigorous by inspecting each gene visually, utilizing a comprehensive set of curation rules, requiring traceable evidence for each gene model, and comparing each predicted peptide to SWISS-PROT and TrEMBL sequences.ResultsAlthough the number of predicted protein-coding genes in Drosophila remains essentially unchanged, the revised annotation significantly improves gene models, resulting in structural changes to 85% of the transcripts and 45% of the predicted proteins. We annotated transposable elements and non-protein-coding RNAs as new features, and extended the annotation of untranslated (UTR) sequences and alternative transcripts to include more than 70% and 20% of genes, respectively. Finally, cDNA sequence provided evidence for dicistronic transcripts, neighboring genes with overlapping UTRs on the same DNA sequence strand, alternatively spliced genes that encode distinct, non-overlapping peptides, and numerous nested genes.ConclusionsIdentification of so many unusual gene models not only suggests that some mechanisms for gene regulation are more prevalent than previously believed, but also underscores the complex challenges of eukaryotic gene prediction. At present, experimental data and human curation remain essential to generate high-quality genome annotations.

Monarch-Initiative/Mondo-Build: 2017-11-10 1.0 Release

This is the first release of MONDO with MONDO IDs as primary. The core ontology is available in 3 formats: http://purl.obolibrary.org/obo/mondo.obo : obo format, use xrefs for equivalence to externals http://purl.obolibrary.org/obo/mondo.owl : owl format, use equivalence axioms to externals http://purl.obolibrary.org/obo/mondo.json : json format, use equivalence axioms to externals Downloads are also available from https://osf.io/2qk53/files/ but it is recommended you use the purls All IDs in Orphanet, OMIM, EFO and DOID can be precisely mapped forward using either equivalence axioms (OWL version) or via xrefs (OBO Format version). Note that for these ID spaces, only precise 1-1 xrefs are included in the release file. Mapping files for particular subsets available on request. In the release following this one, NCIT and GARD will join this precise set. Legacy Support An alternate version of this version of MONDO that retains external IDs and primary IDs is available in the extid/ folder on OSF, or via purls http://purl.obolibrary.org/obo/mondo/extid/mondo.obo http://purl.obolibrary.org/obo/mondo/extid/mondo.owl http://purl.obolibrary.org/obo/mondo/extid/mondo.json Note this support will not be maintained in perpetuity. You are recommended to use the main MONDO release.