Gene Regulatory Network Database

Gene regulation plays a fundamental role in shaping tissue identity, function, and response to perturbation. Regulatory processes are controlled by complex networks of interacting elements, including transcription factors, miRNAs and their target genes. The structure of these networks helps to determine phenotypes and can ultimately influence the development of disease or response to therapy. We developed GRAND (https://grand.networkmedicine.org) as a database for computationally-inferred, context-specific gene regulatory network models that can be compared between biological states, or used to predict which drugs produce changes in regulatory network structure. The database includes 12 468 genome-scale networks covering 36 human tissues, 28 cancers, 1378 unperturbed cell lines, as well as 173 013 TF and gene targeting scores for 2858 small molecule-induced cell line perturbation paired with phenotypic information. GRAND allows the networks to be queried using phenotypic information and visualized using a variety of interactive tools. In addition, it includes a web application that matches disease states to potentially therapeutic small molecule drugs using regulatory network properties.

基因调控在塑造组织特性、功能及对扰动的应答过程中发挥着基础性作用。调控过程由一系列复杂的互作元件网络所控制，这类网络包含转录因子（Transcription Factor, TF）、微小RNA（microRNA, miRNA）及其靶基因。这类网络的结构决定了细胞表型，并最终能够影响疾病的发生发展或治疗应答。
本研究开发了GRAND数据库（网址：https://grand.networkmedicine.org），用于存储经计算推断得到的、具有情境特异性的基因调控网络模型。该数据库支持不同生物学状态下的网络模型比对，也可用于预测可改变调控网络结构的药物。
该数据库包含12468个全基因组规模的调控网络，覆盖36种人体组织、28种癌症类型、1378株未受扰动的细胞系；同时还包含2858个小分子诱导的细胞系扰动数据对应的173013条转录因子及基因靶向评分，并配套了表型信息。GRAND支持基于表型信息对调控网络进行查询，并可通过多种交互式工具实现可视化。此外，该数据库还搭载了一款网页应用，可基于调控网络特征将疾病状态与潜在的治疗性小分子药物进行匹配。

搜集汇总

背景与挑战

背景概述

GRAND是一个基因调控网络数据库，包含大量基于人类组织、癌症、细胞系和小分子药物数据构建的调控网络模型。它提供网络查询、可视化工具以及药物重定位等分析功能，支持生物状态比较和药物效应预测。