Disease-drug pairs revealed by computational genomic connectivity mapping on GBA1 deficient, Gaucher disease mice.

Biochemical and Biophysical Research Communications
Tony YuenMone Zaidi

Abstract

We have reported that, in addition to recapitulating the classical human Gaucher disease (GD1) phenotype, deletion of the glucocerebrosidase (GBA1) gene in mice results in the dysfunction of a diverse population of immune cells. Most of immune-related, non-classical features of GD1, including gammopathies and autoimmune diathesis, are resistant to macrophage-directed therapies. This has prompted a search for newer agents for human GD1. Here, we used high-density microarray on splenic and liver cells from affected GBA1(-/-) mice to establish a gene "signature", which was then utilized to interrogate the Broad Institute database, CMAP. Computational connectivity mapping of disease and drug pairs through CMAP revealed several highly enriched, non-null, mimic and anti-mimic hits. Most notably, two compounds with anti-helminthic properties, namely albendazole and oxamniquine, were identified; these are particularly relevant for future testing as the expression of chitinases is enhanced in GD1.

References

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Citations

Dec 30, 2015·Cell Metabolism·Carmen A ArgmannEric E Schadt
Mar 19, 2014·Proceedings of the National Academy of Sciences of the United States of America·Pramod K MistryMone Zaidi
Jun 11, 2020·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Mone ZaidiTony Yuen
Jul 5, 2017·Proceedings of the National Academy of Sciences of the United States of America·Tong LiuCaigang Liu
Jan 11, 2017·Briefings in Bioinformatics·Aliyu MusaFrank Emmert-Streib

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Datasets Mentioned

BETA
GSE23086

Methods Mentioned

BETA
enzyme replacement therapy

Software Mentioned

IPA
Ingenuity Pathway Analysis ( IPA )
Bioconductor GeneChip Robust Multi - array Average ( GC - RMA )

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