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TIMEOR:一个基于网络的工具,可从多组学数据中揭示时间调控机制。

TIMEOR: a web-based tool to uncover temporal regulatory mechanisms from multi-omics data.

机构信息

Computer Science Department, Brown University, Providence, RI 02912, USA.

Center for Computational and Molecular Biology, Brown University, Providence, RI 02912, USA.

出版信息

Nucleic Acids Res. 2021 Jul 2;49(W1):W641-W653. doi: 10.1093/nar/gkab384.

Abstract

Uncovering how transcription factors regulate their targets at DNA, RNA and protein levels over time is critical to define gene regulatory networks (GRNs) and assign mechanisms in normal and diseased states. RNA-seq is a standard method measuring gene regulation using an established set of analysis stages. However, none of the currently available pipeline methods for interpreting ordered genomic data (in time or space) use time-series models to assign cause and effect relationships within GRNs, are adaptive to diverse experimental designs, or enable user interpretation through a web-based platform. Furthermore, methods integrating ordered RNA-seq data with protein-DNA binding data to distinguish direct from indirect interactions are urgently needed. We present TIMEOR (Trajectory Inference and Mechanism Exploration with Omics data in R), the first web-based and adaptive time-series multi-omics pipeline method which infers the relationship between gene regulatory events across time. TIMEOR addresses the critical need for methods to determine causal regulatory mechanism networks by leveraging time-series RNA-seq, motif analysis, protein-DNA binding data, and protein-protein interaction networks. TIMEOR's user-catered approach helps non-coders generate new hypotheses and validate known mechanisms. We used TIMEOR to identify a novel link between insulin stimulation and the circadian rhythm cycle. TIMEOR is available at https://github.com/ashleymaeconard/TIMEOR.git and http://timeor.brown.edu.

摘要

揭示转录因子如何随时间在 DNA、RNA 和蛋白质水平上调节其靶标,对于定义基因调控网络 (GRN) 并确定正常和疾病状态下的机制至关重要。RNA-seq 是一种使用既定分析阶段测量基因调控的标准方法。然而,目前用于解释有序基因组数据(在时间或空间上)的管道方法都没有使用时间序列模型来在 GRN 中分配因果关系,也没有适应不同的实验设计,或者通过基于网络的平台使用户能够进行解释。此外,迫切需要将有序 RNA-seq 数据与蛋白质-DNA 结合数据集成的方法来区分直接和间接相互作用。我们提出了 TIMEOR(在 R 中使用组学数据进行轨迹推断和机制探索),这是第一个基于网络的自适应时间序列多组学管道方法,它可以推断跨时间的基因调控事件之间的关系。TIMEOR 通过利用时间序列 RNA-seq、基序分析、蛋白质-DNA 结合数据和蛋白质-蛋白质相互作用网络,解决了确定因果调节机制网络的方法的关键需求。TIMEOR 的用户定制方法帮助非编码人员生成新的假设并验证已知的机制。我们使用 TIMEOR 来确定胰岛素刺激与昼夜节律周期之间的新联系。TIMEOR 可在 https://github.com/ashleymaeconard/TIMEOR.githttp://timeor.brown.edu 上获得。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5025/8262710/f31f1e5a2c82/gkab384gra1.jpg

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