Improving the Caenorhabditis elegans Genome Annotation Using Machine Learning

For modern biology, precise genome annotations are of prime importance, as they allow the accurate definition of genic regions. We employ state-of-the-art machine learning methods to assay and improve the accuracy of the genome annotation of the nematode Caenorhabditis elegans. The proposed machine learning system is trained to recognize exons and introns on the unspliced mRNA, utilizing recent advances in support vector machines and label sequence learning. In 87% (coding and untranslated regions) and 95% (coding regions only) of all genes tested in several out-of-sample evaluations, our method correctly identified all exons and introns. Notably, only 37% and 50%, respectively, of the presently unconfirmed genes in the C. elegans genome annotation agree with our predictions, thus we hypothesize that a sizable fraction of those genes are not correctly annotated. A retrospective evaluation of the Wormbase WS120 annotation [1] of C. elegans reveals that splice form predictions on unconfirmed genes in WS120 are inaccurate in about 18% of the considered cases, while our predictions deviate from the truth only in 10%–13%. We experimentally analyzed 20 controversial genes on which our system and the annotation disagree, confirming the superiority of our predictions. While our method correctly predicted 75% of those cases, the standard annotation was never completely correct. The accuracy of our system is further corroborated by a comparison with two other recently proposed systems that can be used for splice form prediction: SNAP and ExonHunter. We conclude that the genome annotation of C. elegans and other organisms can be greatly enhanced using modern machine learning technology

Genome-wide survey and analysis of microsatellites in nematodes, with a focus on the plant-parasitic species Meloidogyne incognita

<p>Abstract</p> <p>Background</p> <p>Microsatellites are the most popular source of molecular markers for studying population genetic variation in eukaryotes. However, few data are currently available about their genomic distribution and abundance across the phylum Nematoda. The recent completion of the genomes of several nematode species, including <it>Meloidogyne incognita</it>, a major agricultural pest worldwide, now opens the way for a comparative survey and analysis of microsatellites in these organisms.</p> <p>Results</p> <p>Using MsatFinder, the total numbers of 1-6 bp perfect microsatellites detected in the complete genomes of five nematode species (<it>Brugia malayi</it>, <it>Caenorhabditis elegans</it>, <it>M. hapla</it>, <it>M. incognita</it>, <it>Pristionchus pacificus</it>) ranged from 2,842 to 61,547, and covered from 0.09 to 1.20% of the nematode genomes. Under our search criteria, the most common repeat motifs for each length class varied according to the different nematode species considered, with no obvious relation to the AT-richness of their genomes. Overall, (AT)_<it>n</it>, (AG)_{<it>n </it>}and (CT)_{<it>n </it>}were the three most frequent dinucleotide microsatellite motifs found in the five genomes considered. Except for two motifs in <it>P. pacificus</it>, all the most frequent trinucleotide motifs were AT-rich, with (AAT)_{<it>n </it>}and (ATT)_{<it>n </it>}being the only common to the five nematode species. A particular attention was paid to the microsatellite content of the plant-parasitic species <it>M. incognita</it>. In this species, a repertoire of 4,880 microsatellite loci was identified, from which 2,183 appeared suitable to design markers for population genetic studies. Interestingly, 1,094 microsatellites were identified in 801 predicted protein-coding regions, 99% of them being trinucleotides. When compared against the InterPro domain database, 497 of these CDS were successfully annotated, and further assigned to Gene Ontology terms.</p> <p>Conclusions</p> <p>Contrasted patterns of microsatellite abundance and diversity were characterized in five nematode genomes, even in the case of two closely related <it>Meloidogyne </it>species. 2,245 di- to hexanucleotide loci were identified in the genome of <it>M. incognita</it>, providing adequate material for the future development of a wide range of microsatellite markers in this major plant parasite.</p