Aquino Jelard, Witoslawski Daniel, Park Steve, Holder Jessica, Amei Amei, Han Mira V
School of Life Sciences, University of Nevada, 4505 S Maryland Pkwy, Las Vegas, NV 89154, USA.
New York Medical College, 40 Sunshine Cottage Road, Valhalla, NY 10595, USA.
Brief Bioinform. 2025 May 1;26(3). doi: 10.1093/bib/bbaf204.
There are primarily two computational approaches to alternative splicing (AS) detection using short reads: splice junction-based and exon-based approaches. Despite their shared goal of addressing the same biological problem, these approaches have not been reconciled before. We devised a novel graph structure and algorithm aimed at mapping between the exonic parts and splicing events detected by the two different methods. Through simulations, we demonstrated disparities in sensitivity and specificity between splice junction-based and exon-based methods. When applied to empirical data, there were large discrepancies in the results, suggesting that the methods are complementary. With the discrepancies localized to individual events and exonic parts, we were able to gain insights into the strengths and weaknesses inherent in each approach. Finally, we integrated the results to generate a comprehensive list of both common and unique AS events detected by both methodologies.
使用短读长进行可变剪接(AS)检测主要有两种计算方法:基于剪接接头的方法和基于外显子的方法。尽管它们解决的是同一个生物学问题,有着共同的目标,但此前这些方法尚未得到统一。我们设计了一种新颖的图结构和算法,旨在对两种不同方法检测到的外显子部分和剪接事件进行映射。通过模拟,我们展示了基于剪接接头的方法和基于外显子的方法在灵敏度和特异性上的差异。当应用于实证数据时,结果存在很大差异,这表明这两种方法是互补的。由于差异局限于个别事件和外显子部分,我们能够深入了解每种方法固有的优缺点。最后,我们整合结果,生成了一份由两种方法检测到的常见和独特AS事件的综合列表。