Disease-drug pairs revealed by computational genomic connectivity mapping on GBA1 deficient, Gaucher disease mice.
Disease-drug pairs revealed by computational genomic connectivity mapping on GBA1 deficient, Gaucher disease mice.
复制标题
通过 GBA1 缺陷的戈谢病小鼠的计算基因组连接图谱揭示疾病-药物对。
DOI：
10.1016/j.bbrc.2012.05.027
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发表时间：
2012
影响因子：
3.1
通讯作者：
Zaidi,Mone
中科院分区：
文献类型：
--
作者：
Yuen,Tony;Iqbal,Jameel;Zhu,Ling-Ling;Sun,Li;Lin,Aiping;Zhao,Hongyu;Liu,Jun;Mistry,PramodK;Zaidi,Mone
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.
