GENCODE: comprehensive gene annotation for human and mouse

描述(由申请人提供)：GENCODE联盟的目标是高精度地注释人类基因组中所有基于证据的基因特征，包括具有交替剪接变体的蛋白质编码基因座、非编码基因座和假基因。根据这一建议，我们的目标是将GENCODE扩展到小鼠基因组，并使用相应的人类和小鼠基因座的比较来改进这两套注释。尽管目前的GENCODE生产项目取得了巨大的进展，至少蛋白质编码基因集目前具有出色的质量，但对所有人类基因的完整注释还远未完成。例如，最近有证据表明，非编码RNA基因的数量远远超过了之前的假设。人们还认识到，从其他细胞类型的转录学研究中仍有大量的可供选择的转录本有待发现。因此，我们的首要目标是继续提高GENCODE人类基因组的覆盖率和准确性。我们的第二个目标是将我们应用于人类的相同注释方法应用于小鼠基因组，以生成人类GENCODE基因集。为了实现这两个目标，我们将整合计算方法、专家手册注释和有针对性的实验方法，就像我们对人类所做的那样。我们还将使用比较的方法来使用产生的鼠标注释来通知和改进人类GENCODE基因集。全面了解基因在人类基因组中的位置和结构是我们理解人类生物学和疾病机制的核心。同样，对于小鼠来说，一个全面的高质量基因集将有助于设计实验，解释基因敲除和由此产生的表型的影响。此外，由于老鼠被用作人类的模型，了解其基因及其与人类基因的关系将有助于了解人类的基因功能。因此，定期发布的GENCODE基因组的结果将对整个人类和小鼠研究人员社区有利。 相关性：全面了解基因在人类基因组中的位置和结构是我们理解人类生物学和疾病机制的核心。由于老鼠被用作人类的模型，了解其基因及其与人类基因的关系也有助于了解人类的基因功能。

DESCRIPTION (provided by applicant): The aim of the GENCODE consortium is to annotate all evidence-based gene features in the human genome at a high accuracy, including protein-coding loci with alternatively splices variants, non-coding loci and pseudogenes. With this proposal we aim to extend GENCODE to the mouse genome and use the comparison of corresponding human and mouse loci to improve both sets of annotation. Despite the tremendous progress of current GENCODE production project, and the current outstanding quality of at least the protein-coding gene set, a complete annotation of all human genes is far from complete. For example, it has recently become clear that the number of non-coding RNA genes is far greater than previously supposed. It is also recognized that there are still substantial numbers of alternative transcripts still to be discovered from transcriptomics studies of additional cell types. Our first aim is therefore to continue to improve the coverage and accuracy of the GENCODE human gene set. Our second aim is to apply to the mouse genome the same annotation approaches as we have applied to human to generate the human GENCODE gene set. To achieve both goals we will integrate computational approaches, expert manual annotation and targeted experimental approaches as we have done for human. We will also use comparative approaches to use the resulting mouse annotation to inform and improve the human GENCODE gene set. A comprehensive knowledge of the location and structure of genes in the human genome is central to our understanding of human biology and the mechanisms of disease. Similarly for mouse, a comprehensive high quality gene set will aid in the design of experiments and the interpretation of the effects of gene knockouts and resulting phenotypes. Also, since mouse is used as a model of human, knowledge of its genes and their relationship to human genes will help inform human gene function. The outputs of regular releases of GENCODE gene sets will therefore be of benefit to the entire community of human and mouse researchers. RELEVANCE: A comprehensive knowledge of the location and structure of genes in the human genome is central to our understanding of human biology and the mechanisms of disease. Since mouse is used as a model of human, knowledge of its genes and their relationship to human genes also helps inform human gene function.