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Global detection and identification of developmental stage specific transcripts in mouse brain using subtractive cross-screening algorithm

机译：利用减性交叉筛选算法对小鼠大脑发育阶段特定转录本进行全局检测和鉴定

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Background: Pre-mRNA splicing is a crucial step for genetic regulation and accounts largely for downstream translational diversity. The current time of biological research is characterized by advances in functional genomics study and the understanding of the pre-mRNA splicing process has thus become a major portal for biologists to gain insights into the complex gene regulatory mechanism. The intranuclear alternative splicing process can form a variety of genomic transcripts that modulate the growth and development of an organism, particularly in the immune and neural systems. Methods: In the current study, we investigated and identified alternative splicing transcripts at different stages of embryonic mouse brain morphogenesis using subtractive cross-screening algorithm. Results: A total of 195 candidate transcripts were found during organogenesis; 1629 identified at fetus stage, 116 in juvenile and 148 transcripts from adulthood. To document our findings, we developed a database named DMBAS, which can be accessed through the link: http://173.234.48.5/DMBAS. We further investigated the alternative splicing products obtained in our experiment and noted the existence of chromosome preference between prenatal and postnatal transcripts. Additionally, the distribution of splicing sites and the splicing types were found to have distinct genomic features at varying stages of brain development. The majority of identified alternative splices (72.3%) at fetus stage were confirmed later using separate RNA-seq data sets. Conclusion: This study is a comprehensive profiling of alternative splicing transcripts of mouse brain morphogenesis using advanced computational algorithm. A series of developmental stage specific transcripts, as well as their splicing sites and chromosome preferences were revealed in the current study. Our findings and the related online database would form a solid foundation for studies of broader biological significance and paved the way for future investigations in relevant human brain diseases.
机译：背景：mRNA前剪接是遗传调控的关键步骤，在很大程度上解释了下游翻译的多样性。当前生物学研究的时代以功能基因组学研究的发展为特征，因此对mRNA前剪接过程的理解已成为生物学家深入了解复杂基因调控机制的重要门户。核内替代剪接过程可以形成多种基因组转录本，这些转录本可以调节生物体的生长和发育，特别是在免疫和神经系统中。方法：在当前的研究中，我们使用减性交叉筛选算法研究并鉴定了在胚胎小鼠脑形态发生的不同阶段的可变剪接转录本。结果：在器官发生过程中共发现195个候选转录本。在胎儿期鉴定出1629份，在青少年期鉴定出116份，从成年期鉴定出148份。为了记录我们的发现，我们开发了一个名为DMBAS的数据库，可以通过以下链接访问该数据库：http://173.234.48.5/DMBAS。我们进一步研究了在我们的实验中获得的替代剪接产物，并指出了产前和产后转录本之间存在染色体偏好。此外，发现剪接位点的分布和剪接类型在大脑发育的不同阶段具有独特的基因组特征。后来使用单独的RNA-seq数据集确认了胎儿期大多数已鉴定的替代剪接（72.3％）。结论：本研究是使用高级计算算法对小鼠脑形态发生的其他剪接转录本进行的综合分析。这项研究揭示了一系列发育阶段的特定转录本，以及它们的剪接位点和染色体偏好。我们的发现和相关的在线数据库将为更广泛的生物学意义的研究奠定坚实的基础，并为未来在有关人脑疾病中的研究铺平道路。

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