Systematic improvement of Xenopus gene annotations and reference genomes

描述(由申请人提供)：非洲爪哇是一个非凡的生物医学研究模型，提供了许多促进基础和应用研究的实验优势。近年来，基因组测序将蛙类转变为一种强大的基因组和蛋白质组工具，用于了解基因、染色质和多种细胞过程的调节功能，进一步推动了非洲爪哇作为系统生物学工具的发展。这笔赠款的首要目标是整合和分析这些数据，以改进非洲爪哇和非洲爪哇的基因注释和参考基因组，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能够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，并产生高质量的基因注释。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点测序整合到非洲爪哇基因结构的预测中。(2)通过专家馆长和计算生物学家之间紧密而快速的反馈循环，有效地将人工管理和批量分析相结合，以系统地改进基因结构注释，为进展产生定量度量。(3)系统地改进草案基因组以包括完整的基因，通过使用现有的和新产生的数据来(A)填补或部分填补基因的空白，(B)修复序列中的局部错误(例如，组装中的缺失)，以及(C)改善基因组的全球组织。在整个项目中，将优先考虑更广泛的非洲爪哇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.