Exploring the cellular basis of human disease through a large-scale mapping of deleterious genes to cell types

Genome Medicine
Alex J CornishMichael J E Sternberg

Abstract

Each cell type found within the human body performs a diverse and unique set of functions, the disruption of which can lead to disease. However, there currently exists no systematic mapping between cell types and the diseases they can cause. In this study, we integrate protein-protein interaction data with high-quality cell-type-specific gene expression data from the FANTOM5 project to build the largest collection of cell-type-specific interactomes created to date. We develop a novel method, called gene set compactness (GSC), that contrasts the relative positions of disease-associated genes across 73 cell-type-specific interactomes to map genes associated with 196 diseases to the cell types they affect. We conduct text-mining of the PubMed database to produce an independent resource of disease-associated cell types, which we use to validate our method. The GSC method successfully identifies known disease-cell-type associations, as well as highlighting associations that warrant further study. This includes mast cells and multiple sclerosis, a cell population currently being targeted in a multiple sclerosis phase 2 clinical trial. Furthermore, we build a cell-type-based diseasome using the cell types identified as manifesting eac...Continue Reading

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Citations

Jun 17, 2016·Bioinformatics·Shahin Mohammadi, Ananth Grama
Apr 29, 2021·Annual Review of Biomedical Engineering·Amr A AbdeenKrishanu Saha

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Methods Mentioned

BETA
biopsies

Clinical Trials Mentioned

NCT01433497

Software Mentioned

DisGeNET
Ensembl
Uberon
Entrez Programming Utilities ( eUtils )
R
edgeR R package
PRINCE
biomaRt R package
igraph R package
FANTOM5

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