Xenopus is an extraordinary model for biomedical research that offers many experimental advantages that facilitate both basic and applied research. In recent years, genome sequencing has transformed the frog into a powerful genomic and proteomic tool for understanding the regulatory function of genes, chromatin, and multiple cellular processes, further advancing Xenopus as a tool for systems biology. The overarching goal of this grant is to integrate and analyze this data to improve the gene annotations and reference genomes for Xenopus tropicalis and X. laevis so that the greater community of developmental biologists, stem cell and regeneration biologists, and cell biologists can access and capitalize on this data. A challenge is to carry out this integration, and the generation of a high quality gene annotation, in a systematic but cost-effective manner. New methods are needed to efficiently integrate this data. We have three aims: (1) Integrate RNA-seq, epigenetic maps, and transcriptional start site sequencing into prediction of Xenopus gene structures. (2) Efficiently combine manual curation and bulk analysis to systematically improve gene structure annotation through a tight and rapid feedback loop between an expert curator and computational biologists, producing quantitative metrics for progress. (3) Systematically improve draft genomes to include complete genes by using existing and newly generated data to (a) close or partially fill gaps in genes, (b) fix local errors in sequence (e.g., deletions in assembly), and (c) improve global organization of genome. Throughout the project, priority will be placed on genic regions of interest to the broader Xenopus community.
Together Xenopus tropicalis and X laevis represent an extraordinarily powerful model system for biomedical research. This project will develop innovative approaches to produce a high quality gene annotation of the Xenopus genomes in parallel with improvements in the quality of genome assembly in genic regions. This annotation will enable genomically-enabled systems biology approaches to fundamental and applied problems in biomedicine.