As the number of RNA-seq datasets that become available to explore transcriptome diversity increases, so does the need for easy-to-use comprehensive computational workflows. Many available tools facilitate analyses of one of the two major mechanisms of transcriptome diversity, namely, differential expression of isoforms due to alternative splicing, while the second major mechanism—RNA editing due to post-transcriptional changes of individual nucleotides—remains under-appreciated. Both these mechanisms play an essential role in physiological and diseases processes, including cancer and neurological disorders. However, elucidation of RNA editing events at transcriptome-wide level requires increasingly complex computational tools, in turn resulting in a steep entrance barrier for labs who are interested in high-throughput variant calling applications on a large scale but lack the manpower and/or computational expertise. Here we present an easy-to-use, fully automated, computational pipeline (Automated Isoform Diversity Detector, AIDD) that contains open source tools for various tasks needed to map transcriptome diversity, including RNA editing events. To facilitate reproducibility and avoid system dependencies, the pipeline is contained within a pre-configured VirtualBox environment. The analytical tasks and format conversions are accomplished via a set of automated scripts that enable the user to go from a set of raw data, such as fastq files, to publication-ready results and figures in one step. A publicly available dataset of Zika virus-infected neural progenitor cells is used to illustrate AIDD’s capabilities. AIDD pipeline offers a user-friendly interface for comprehensive and reproducible RNA-seq analyses. Among unique features of AIDD are its ability to infer RNA editing patterns, including ADAR editing, and inclusion of Guttman scale patterns for time series analysis of such editing landscapes. AIDD-based results show importance of diversity of ADAR isoforms, key RNA editing enzymes linked with the innate immune system and viral infections. These findings offer insights into the potential role of ADAR editing dysregulation in the disease mechanisms, including those of congenital Zika syndrome. Because of its automated all-inclusive features, AIDD pipeline enables even a novice user to easily explore common mechanisms of transcriptome diversity, including RNA editing landscapes.

中文翻译：

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自动化亚型多样性检测器（AIDD）：用于研究RNA序列数据的转录组多样性的管道

随着可用于探索转录组多样性的RNA-seq数据集数量的增加，对易于使用的综合计算工作流程的需求也在增加。许多可用的工具有助于分析转录组多样性的两个主要机制之一，即，由于可变剪接导致的同工型差异表达，而第二个主要机制（由于单个核苷酸的转录后变化导致的RNA编辑）仍然被低估。这两种机制在包括癌症和神经系统疾病在内的生理和疾病过程中都起着至关重要的作用。但是，要在转录组范围内阐明RNA编辑事件，就需要越来越复杂的计算工具，反过来给那些对大规模高通量呼叫应用程序感兴趣但缺乏人力和/或计算专业知识的实验室带来了陡峭的入口壁垒。在这里，我们介绍了一个易于使用的，全自动的计算管道（自动异构形式多样性检测器，AIDD），其中包含用于绘制转录组多样性所需的各种任务的开源工具，包括RNA编辑事件。为了促进可重复性并避免系统依赖性，该管道包含在预先配置的VirtualBox环境中。分析任务和格式转换是通过一组自动化脚本完成的，这些脚本使用户能够一步一步地从一组原始数据（例如fastq文件）转到可发布的结果和图形。寨卡病毒感染的神经祖细胞的公开数据集用于说明AIDD的功能。AIDD管道提供了用户友好的界面，可进行全面且可重复的RNA序列分析。AIDD的独特功能包括推断RNA编辑模式（包括ADAR编辑）的能力，以及包含Guttman尺度模式的时间序列分析此类编辑格局的能力。基于AIDD的结果表明，ADAR亚型，与先天免疫系统相关的关键RNA编辑酶和病毒感染的多样性非常重要。这些发现为深入了解ADAR编辑失调在疾病机制（包括先天性寨卡综合症）中的潜在作用提供了见识。由于其自动化的全包功能，