Supplementary Material for: DoriTool: A Bioinformatics Integrative Tool for Post-Association Functional Annotation

The emergence of high-throughput data in biology has increased the need for functional in silico analysis and prompted the development of integrative bioinformatics tools to facilitate the obtainment of biologically meaningful data. In this paper, we present DoriTool, a comprehensive, easy, and friendly pipeline integrating biological data from different functional tools. The tool was designed with the aim to maximize reproducibility and reduce the working time of the researchers, especially of those with limited bioinformatics skills, and to help them with the interpretation of the results. DoriTool is based upon an integrative strategy implemented following a modular design pattern. Using scripts written in Bash, Perl and R, it performs a functional in silico analysis annotation at mutation/variant level, gene level, pathway level and network level by combining up-to-date functional and genomic data and integrating also third-party bioinformatics tools in a pipeline. DoriTool uses GRCh37 human assembly and online mode. DoriTool provides nice visual reports including variant annotation, linkage disequilibrium proxies, gene annotation, gene ontology analysis, expression quantitative trait loci results from Genotype-Tissue Expression (GTEx) and coloured pathways. Here, we also show DoriTool functionalities by applying it to a dataset of 13 variants associated with prostate cancer. Project development, released code libraries, GitHub repository (https://github.com/doritool) and documentation are hosted at https://doritool.github.io/. DoriTool is, to our knowledge, the most complete bioinformatics tool offering functional in silico annotation of variants previously associated with a trait of interest, shedding light on the underlying biology and helping the researchers in the interpretation and discussion of the results.

随着生物学领域高通量数据的涌现，对功能虚拟（in silico）分析的需求日益增长，也推动了整合型生物信息学工具的开发，以助力获取具有生物学意义的数据集。本研究中，我们介绍了DoriTool——一款整合了多款功能工具所产生的生物学数据的全面、易用且友好的流程化工具。该工具的设计目标在于最大化研究结果的可重复性，缩减研究人员的工作时长，尤其针对生物信息学技能储备有限的研究者，并辅助其完成结果解读工作。DoriTool基于模块化设计范式所实现的整合策略进行构建。借助Bash、Perl与R语言编写的脚本，DoriTool可整合最新的功能组学与基因组学数据，并将第三方生物信息学工具整合至流程中，从而在突变/变异水平、基因水平、通路水平以及网络水平开展功能虚拟分析注释工作。DoriTool采用GRCh37人类基因组组装版本，并支持在线运行模式。DoriTool可生成美观的可视化报告，涵盖变异注释、连锁不平衡（linkage disequilibrium）代理位点、基因注释、基因本体（gene ontology, GO）分析、源自基因型-组织表达（Genotype-Tissue Expression, GTEx）数据库的表达数量性状位点分析结果，以及着色通路图。本研究同时通过将DoriTool应用于一组包含13个与前列腺癌相关的变异的数据集，展示了该工具的各项功能。本项目的开发过程、已发布的代码库、GitHub仓库（https://github.com/doritool）以及相关文档均托管于https://doritool.github.io/。据我们所知，DoriTool是目前最为全面的生物信息学工具之一，可为此前与目标性状相关的变异提供功能虚拟注释，阐明其背后的生物学机制，并辅助研究人员开展结果解读与讨论工作。