Novel and improvedCaenorhabditis briggsaegene models generated by community curation
Authors: Moya Nicolas D. , Stevens Lewis , Miller Isabella R. , Sokol Chloe E. , Galindo Joseph L. , Bardas Alexandra D. , Koh Edward S. H. , Rozenich Justine , Yeo Cassia , Xu Maryanne , Andersen Erik C. 
Published: May 2023

Background

The nematodeCaenorhabditis briggsaehas been used as a model for genomics studies compared toCaenorhabditis elegansbecause of its striking morphological and behavioral similarities. These studies yielded numerous findings that have expanded our understanding of nematode development and evolution. However, the potential ofC. briggsaeto study nematode biology is limited by the quality of its genome resources. The reference genome and gene models for theC. briggsaelaboratory strain AF16 have not been developed to the same extent asC. elegans. The recent publication of a new chromosome-level reference genome for QX1410, aC. briggsaewild strain closely related to AF16, has provided the first step to bridge the gap betweenC. elegansandC. briggsaegenome resources. Currently, the QX1410 gene models consist of protein-coding gene predictions generated from short- and long-read transcriptomic data. Because of the limitations of gene prediction software, the existing gene models for QX1410 contain numerous errors in their structure and coding sequences. In this study, a team of researchers manually inspected over 21,000 software-derived gene models and underlying transcriptomic data to improve the protein-coding gene models of theC. briggsaeQX1410 genome.

Results

We designed a detailed workflow to train a team of nine students to manually curate genes using RNA read alignments and predicted gene models. We manually inspected the gene models using the genome annotation editor, Apollo, and proposed corrections to the coding sequences of over 8,000 genes. Additionally, we modeled thousands of putative isoforms and untranslated regions. We exploited the conservation of protein sequence length betweenC. briggsaeandC. elegansto quantify the improvement in protein-coding gene model quality before and after curation. Manual curation led to a substantial improvement in the protein sequence length accuracy of QX1410 genes. We also compared the curated QX1410 gene models against the existing AF16 gene models. The manual curation efforts yielded QX1410 gene models that are similar in quality to the extensively curated AF16 gene models in terms of protein-length accuracy and biological completeness scores. Collinear alignment analysis between the QX1410 and AF16 genomes revealed over 1,800 genes affected by spurious duplications and inversions in the AF16 genome that are now resolved in the QX1410 genome.

Conclusions

Community-based, manual curation using transcriptome data is an effective approach to improve the quality of software-derived protein-coding genes. Comparative genomic analysis using a related species with high-quality reference genome(s) and gene models can be used to quantify improvements in gene model quality in a newly sequenced genome. The detailed protocols provided in this work can be useful for future large-scale manual curation projects in other species. The chromosome-level reference genome for theC. briggsaestrain QX1410 far surpasses the quality of the genome of the laboratory strain AF16, and our manual curation efforts have brought the QX1410 gene models to a comparable level of quality to the previous reference, AF16. The improved genome resources forC. briggsaeprovide reliable tools for the study ofCaenorhabditisbiology and other related nematodes.