Liu Yu, Alakwaa Fadhl
Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor 48109 MI, United States.
Department of Internal Medicine, Nephrology Division, University of Michigan, Ann Arbor 48109 MI, United States.
NAR Genom Bioinform. 2025 Sep 5;7(3):lqaf123. doi: 10.1093/nargab/lqaf123. eCollection 2025 Sep.
The dynamics of transcriptional elongation influence many biological activities, such as RNA splicing, polyadenylation, and nuclear export. To quantify the elongation rate, a typical method is to treat cells with drugs that inhibit RNA polymerase II (Pol II) from entering the gene body and then track Pol II using Pro-seq or Gro-seq. However, the downstream data analysis is challenged by the problem of identifying the transition point between the gene regions inhibited by the drug and not, which is necessary to calculate the transcription rate. Although the traditional hidden Markov model (HMM) can be used to solve it, this method is complicated with its hidden variable and many parameters to be estimated. Hence, we developed the R package , which identifies the transition point with a novel least sum of squares (LSS) method and calculates the elongation rate accordingly. In addition, also covers other functions frequently used in transcription dynamic study, including metagene plotting, pause index calculation, gene structure analysis, etc. The effectiveness of this package is proved by its performance on three Pro-seq or Gro-seq datasets, showing higher accuracy than HMM. is freely available at https://github.com/yuabrahamliu/proRate or https://github.com/FADHLyemen/proRate.
转录延伸的动力学影响许多生物学活动,如RNA剪接、聚腺苷酸化和核输出。为了量化延伸速率,一种典型的方法是用抑制RNA聚合酶II(Pol II)进入基因体的药物处理细胞,然后使用Pro-seq或Gro-seq追踪Pol II。然而,下游数据分析面临着识别药物抑制区域和未抑制区域之间的转换点这一问题的挑战,而这对于计算转录速率是必要的。虽然传统的隐马尔可夫模型(HMM)可用于解决此问题,但该方法因其存在隐藏变量和许多需要估计的参数而较为复杂。因此,我们开发了R包,它用一种新颖的最小二乘和(LSS)方法识别转换点并据此计算延伸速率。此外, 还涵盖了转录动态研究中常用的其他功能,包括元基因绘图、暂停指数计算、基因结构分析等。该软件包在三个Pro-seq或Gro-seq数据集上的表现证明了其有效性,显示出比HMM更高的准确性。 可在https://github.com/yuabrahamliu/proRate或https://github.com/FADHLyemen/proRate上免费获取。