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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Network- and enrichment-based inference of phenotypes and targets from large-scale disease maps
npj Systems Biology and Applications, Volume 8, No. 1, Article 13, Year 2022
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Description
Complex diseases are inherently multifaceted, and the associated data are often heterogeneous, making linking interactions across genes, metabolites, RNA, proteins, cellular functions, and clinically relevant phenotypes a high-priority challenge. Disease maps have emerged as knowledge bases that capture molecular interactions, disease-related processes, and disease phenotypes with standardized representations in large-scale molecular interaction maps. Various tools are available for disease map analysis, but an intuitive solution to perform in silico experiments on the maps in a wide range of contexts and analyze high-dimensional data is currently missing. To this end, we introduce a two-dimensional enrichment analysis (2DEA) approach to infer downstream and upstream elements through the statistical association of network topology parameters and fold changes from molecular perturbations. We implemented our approach in a plugin suite for the MINERVA platform, providing an environment where experimental data can be mapped onto a disease map and predict potential regulatory interactions through an intuitive graphical user interface. We show several workflows using this approach and analyze two RNA-seq datasets in the Atlas of Inflammation Resolution (AIR) to identify enriched downstream processes and upstream transcription factors. Our work improves the usability of disease maps and increases their functionality by facilitating multi-omics data integration and exploration. © 2022, The Author(s).
Authors & Co-Authors
Hoch, Matti
Germany, Rostock
Universität Rostock
Smita, Suchi
Germany, Rostock
Universität Rostock
Cesnulevicius, Konstantin
Germany, Baden-baden
Heel Gmbh
Lescheid, David W.
Germany, Baden-baden
Heel Gmbh
Schultz, Myron
Germany, Baden-baden
Heel Gmbh
Wolkenhauer, Olaf
Germany, Rostock
Universität Rostock
Germany, Freising
Leibniz-institut Für Lebensmittel-systembiologie an Der Technischen Universität München
Gupta, Shailendra Kumar
Germany, Rostock
Universität Rostock
Statistics
Citations: 6
Authors: 7
Affiliations: 3
Identifiers
Doi:
10.1038/s41540-022-00222-z
ISSN:
20567189
Research Areas
Environmental