Calculating the most likely intron splicing orders in S. pombe , fruit fly, Arabidopsis thaliana , and humans
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METHODOLOGY ARTICLE
Open Access
Calculating the most likely intron splicing orders in S. pombe, fruit fly, Arabidopsis thaliana, and humans Meng Li*
*Correspondence: [email protected] CAS‑MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
Abstract Background: Introns have been shown to be spliced in a defined order, and this order influences both alternative splicing regulation and splicing fidelity, but previous studies have only considered neighbouring introns. The detailed intron splicing order remains unknown. Results: In this work, a method was developed that can calculate the intron splicing orders of all introns in each transcript. A simulation study showed that this method can accurately calculate intron splicing orders. I further applied this method to real S. pombe, fruit fly, Arabidopsis thaliana, and human sequencing datasets and found that intron splicing orders change from gene to gene and that humans contain more not in-order spliced transcripts than S. pombe, fruit fly and Arabidopsis thaliana. In addition, I reconfirmed that the first introns in humans are spliced slower than those in S. pombe, fruit fly, and Arabidopsis thaliana genome-widely. Both the calculated most likely orders and the method developed here are available on the web. Conclusions: A novel computational method was developed to calculate the intron splicing orders and applied the method to real sequencing datasets. I obtained intron splicing orders for hundreds or thousands of genes in four organisms. I found humans contain more number of not in-order spliced transcripts. Keywords: Splicing, Intron splicing order, Most likely order, Bayesian network
Background Splicing has been shown to be an integrated process coupled with transcription [1], and the co-transcriptional nature of splicing has been shown in various ways, such as via the sawtooth pattern of RNA-seq [2], real-time imaging [3], nuclear fraction RNA-seq [4], and electron imaging for direct visualization of co-transcription [5]. These results showed that most introns in higher organisms are co-transcriptionally spliced. One natural line of thought is that since splicing is coupled with transcription, the splicing order may also be consistent with the transcriptional direction [6]. However, several recent studies have shown that this is not the case; these studies used long-read sequencing or bulk short-read sequencing to find that splicing is a co-transcriptional © The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated other
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