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

Author:

Ben Guebila Marouen1ORCID,Lopes-Ramos Camila M1,Weighill Deborah1ORCID,Sonawane Abhijeet Rajendra2,Burkholz Rebekka1,Shamsaei Behrouz3,Platig John4,Glass Kimberly14,Kuijjer Marieke L56ORCID,Quackenbush John14ORCID

Affiliation:

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

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

3. Division of Biostatistics and Bioinformatics, Department of Environmental and Public Health Sciences, University of Cincinnati College of Medicine, Cincinnati, OH, USA

4. Channing Division of Network Medicine, Department of Medicine, Harvard Medical School and Brigham and Women’s Hospital, Boston, MA, USA

5. Center for Molecular Medicine Norway, Faculty of Medicine, University of Oslo, Oslo, Norway

6. Leiden University Medical Center, Leiden, The Netherlands

Abstract

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.

Funder

Norwegian Research Council

Helse Sør-Øst

University of Oslo

National Institutes of Health

National Heart, Lung, and Blood Institute

National Cancer Institute

Publisher

Oxford University Press (OUP)

Subject

Genetics

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