Systematic improvement of Xenopus gene annotations and reference genomes

描述（由申请人提供）：非洲爪蟾是生物医学研究的一个非凡的模型，提供了许多实验优势，促进基础和应用研究。近年来，基因组测序已经将青蛙转变为一种强大的基因组和蛋白质组学工具，用于了解基因，染色质和多个细胞过程的调节功能，进一步推进非洲爪蟾作为系统生物学的工具。这项资助的首要目标是整合和分析这些数据，以改善热带爪蟾和非洲爪蟾的基因注释和参考基因组。laevis，以便更多的发育生物学家，干细胞和再生生物学家以及细胞生物学家可以访问和利用这些数据。一个挑战是以系统但具有成本效益的方式进行这种整合，并生成高质量的基因注释。需要新的方法来有效地整合这些数据。我们有三个目标：（1）将RNA-seq、表观遗传图谱和转录起始位点测序整合到非洲爪蟾基因结构的预测中。(2)有效地将联合收割机手动管理和批量分析相结合，通过专家管理员和计算生物学家之间紧密而快速的反馈循环，系统地改进基因结构注释，从而为进展提供定量指标。(3)通过使用现有的和新生成的数据来系统地改进草图基因组以包括完整的基因，以（a）关闭或部分填充基因中的缺口，（B）修复序列中的局部错误（例如，组装中的缺失），和（c）改善基因组的整体组织。在整个项目中，将优先考虑更广泛的非洲爪蟾社区感兴趣的基因区域。

DESCRIPTION (provided by applicant): 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.