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GRAND:一个跨人类条件的基因调控网络模型数据库。

GRAND: a database of gene regulatory network models across human conditions.

机构信息

Department of Biostatistics, Harvard School of Public Health, Boston, MA, USA.

Center for Interdisciplinary Cardiovascular Sciences, Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA02115, USA.

出版信息

Nucleic Acids Res. 2022 Jan 7;50(D1):D610-D621. doi: 10.1093/nar/gkab778.

Abstract

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.

摘要

基因调控在塑造组织身份、功能和对干扰的反应方面起着至关重要的作用。调控过程受转录因子、miRNA 及其靶基因等相互作用元件的复杂网络控制。这些网络的结构有助于确定表型,最终可能影响疾病的发展或对治疗的反应。我们开发了 GRAND(https://grand.networkmedicine.org)作为一个数据库,用于计算推断、上下文特定的基因调控网络模型,这些模型可以在不同的生物状态之间进行比较,也可以用于预测哪些药物会改变调控网络结构。该数据库包含 12468 个全基因组网络,涵盖 36 个人体组织、28 种癌症、1378 种未受干扰的细胞系,以及 173013 个 TF 和基因靶向分数,用于 2858 种小分子诱导的细胞系扰动,并与表型信息配对。GRAND 允许使用表型信息查询网络,并使用各种交互式工具进行可视化。此外,它还包括一个网络应用程序,该程序使用调控网络特性将疾病状态与潜在的治疗性小分子药物相匹配。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/703b/8728257/582ccb8182f7/gkab778gra1.jpg

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