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基于标准 RNA-seq 数据的 IPAFinder 揭示的癌相关内含子多聚腺苷酸化动态及其潜在调控因子。

Cancer-associated dynamics and potential regulators of intronic polyadenylation revealed by IPAFinder using standard RNA-seq data.

机构信息

State Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and Development, Human Phenome Institute, School of Life Sciences and Huashan Hospital, Fudan University, Shanghai 200438, P.R. China.

School of Life Science and Technology, ShanghaiTech University, Shanghai 200438, P.R. China.

出版信息

Genome Res. 2021 Nov;31(11):2095-2106. doi: 10.1101/gr.271627.120. Epub 2021 Sep 2.

Abstract

Intronic polyadenylation (IpA) usually leads to changes in the coding region of an mRNA, and its implication in diseases has been recognized, although at its very beginning status. Conveniently and accurately identifying IpA is of great importance for further evaluating its biological significance. Here, we developed IPAFinder, a bioinformatic method for the de novo identification of intronic poly(A) sites and their dynamic changes from standard RNA-seq data. Applying IPAFinder to 256 pan-cancer tumor/normal pairs across six tumor types, we discovered 490 recurrent dynamically changed IpA events, some of which are novel and derived from cancer-associated genes such as , , and Furthermore, IPAFinder revealed that IpA could be regulated by factors related to splicing and mA modification. In summary, IPAFinder enables the global discovery and characterization of biologically regulated IpA with standard RNA-seq data and should reveal the biological significance of IpA in various processes.

摘要

内含子多聚腺苷酸化(IpA)通常会导致 mRNA 编码区发生变化,尽管其在疾病中的作用仍处于起步阶段,但已得到认可。方便、准确地识别 IpA 对于进一步评估其生物学意义非常重要。在这里,我们开发了 IPAFinder,这是一种从标准 RNA-seq 数据中从头鉴定内含子 poly(A) 位点及其动态变化的生物信息学方法。将 IPAFinder 应用于六种肿瘤类型的 256 对泛癌肿瘤/正常对,我们发现了 490 个反复出现的动态变化的 IpA 事件,其中一些是新颖的,源自癌症相关基因,如 、 、 和 。此外,IPAFinder 还揭示了 IpA 可以受到与剪接和 mA 修饰相关的因子的调节。总之,IPAFinder 可以使用标准 RNA-seq 数据实现对生物调控的 IpA 的全局发现和特征描述,这应该会揭示 IpA 在各种过程中的生物学意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35fc/8559711/c3d0ded196ab/2095f01.jpg

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