Structure-guided isoform identification for the human transcriptome.
Structure-guided isoform identification for the human transcriptome.
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DOI：
10.7554/elife.82556
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发表时间：
2022-12-15
期刊：
影响因子：
7.7
通讯作者：
Salzberg SL
中科院分区：
文献类型：
--
作者：
Sommer MJ;Cha S;Varabyou A;Rincon N;Park S;Minkin I;Pertea M;Steinegger M;Salzberg SL
近年来发展起来的高精度蛋白质三维结构预测方法为基因组和蛋白质组研究开辟了新的途径。我们探索了一个新的假设，在基因组注释，即计算预测的结构是否可以帮助确定多个可能的基因异构体代表一个功能蛋白质产物。在蛋白质结构预测的指导下，我们评估了超过230，000种人类蛋白质编码基因的同种型，这些基因是从许多人体组织的10，000多个RNA测序实验中组装而成的。从这组组装的转录本中，我们鉴定出数百种亚型，与最新人类基因数据库中的典型亚型相比，它们具有更可靠的预测结构和潜在的上级功能。我们用例子说明了我们的新方法，其中结构结合表达和进化证据提供了功能指南。此外，我们还提供了完整的结构集，作为更好地了解人类基因及其亚型功能的资源。这些结果证明了蛋白质结构预测作为基因组注释工具的前景，使我们能够完善即使是最高度策划的人类蛋白质目录。更一般地说，我们展示了一种实用的，结构指导的方法，可用于增强任何基因组的注释。
Recently developed methods to predict three-dimensional protein structure with high accuracy have opened new avenues for genome and proteome research. We explore a new hypothesis in genome annotation, namely whether computationally predicted structures can help to identify which of multiple possible gene isoforms represents a functional protein product. Guided by protein structure predictions, we evaluated over 230,000 isoforms of human protein-coding genes assembled from over 10,000 RNA sequencing experiments across many human tissues. From this set of assembled transcripts, we identified hundreds of isoforms with more confidently predicted structure and potentially superior function in comparison to canonical isoforms in the latest human gene database. We illustrate our new method with examples where structure provides a guide to function in combination with expression and evolutionary evidence. Additionally, we provide the complete set of structures as a resource to better understand the function of human genes and their isoforms. These results demonstrate the promise of protein structure prediction as a genome annotation tool, allowing us to refine even the most highly curated catalog of human proteins. More generally we demonstrate a practical, structure-guided approach that can be used to enhance the annotation of any genome.