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 TSC1, SPERD2, and CCND2. Furthermore, IPAFinder revealed that IpA could be regulated by factors related to splicing and m⁶A 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.

中文翻译：

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IPAFinder 使用标准 RNA-seq 数据揭示了内含子多聚腺苷酸化的癌症相关动力学和潜在调节因子

内含子多聚腺苷酸化 (IpA) 通常会导致 mRNA 编码区的变化，并且它在疾病中的影响已被认识到，尽管它处于最初的状态。方便准确地鉴定 IpA 对于进一步评估其生物学意义具有重要意义。在这里，我们开发了 IPAFinder，这是一种从标准 RNA-seq 数据中从头识别内含子 poly(A) 位点及其动态变化的生物信息学方法。将 IPAFinder 应用于 6 种肿瘤类型的 256 个泛癌肿瘤/正常对，我们发现了 490 个复发性动态变化的 IpA 事件，其中一些是新的并且源自癌症相关基因，如TSC1、SPERD2和CCND2. 此外，IPAFinder 揭示了 IpA 可能受到与剪接和 m ⁶ A 修饰相关的因素的调节。总之，IPAFinder 能够使用标准 RNA-seq 数据对生物调节的 IpA 进行全球发现和表征，并应揭示 IpA 在各种过程中的生物学意义。