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将受体组基因与其配体进行匹配以研究旁分泌/自分泌信号系统。

Matching receptome genes with their ligands for surveying paracrine/autocrine signaling systems.

作者信息

Ben-Shlomo Izhar, Rauch Rami, Avsian-Kretchmer Orna, Hsueh Aaron J W

机构信息

Division of Reproductive Biology, Department of Obstetrics and Gynecology, Stanford University Medical Center, Stanford University School of Medicine, Stanford, California 94305-5317, USA.

出版信息

Mol Endocrinol. 2007 Aug;21(8):2009-14. doi: 10.1210/me.2007-0087. Epub 2007 Jun 5.

DOI:10.1210/me.2007-0087
PMID:17550980
Abstract

Sequencing of genomes from diverse organisms facilitates studies on the repertoire of genes involved in intercellular signaling. Extending previous efforts to annotate most human plasma membrane receptors in the Human Plasma Membrane Receptome database, we matched cognate ligands with individual receptors by surveying the published literature. In the updated online database we called "liganded receptome," users can search for individual ligands or receptors to reveal their pairing partners and browse through receptor or ligand families to identify relationships between ligands and receptors in their respective families. Because local signaling systems are prevalent in diverse normal and diseased tissues, we used the liganded receptome knowledgebase to interrogate DNA microarray datasets for genome-wide analyses of potential paracrine/autocrine signaling systems. In addition to viewing ligand-receptor coexpression based on precomputed DNA microarray data, users can submit their own microarray data to perform online genome-wide searches for putative paracrine/autocrine signaling systems. Investigation of transcriptome data based on liganded receptome allows the discovery of paracrine/autocrine signaling for known ligand-receptor pairs in previously uncharacterized tissues or developmental stages. The present annotation of ligand-receptor pairs also identifies orphan receptors and ligands without known interacting partners in select families. Because hormonal ligands within the same family usually interact with paralogous receptors, this genomic approach could also facilitate matching of orphan receptors and ligands. The liganded receptome is accessible at http://receptome.stanford.edu.

摘要

对来自不同生物体的基因组进行测序有助于研究参与细胞间信号传导的基因库。在之前努力注释人类质膜受体组数据库中大多数人类质膜受体的基础上,我们通过查阅已发表的文献,将同源配体与单个受体进行了匹配。在我们称为“配体化受体组”的更新在线数据库中,用户可以搜索单个配体或受体以揭示它们的配对伙伴,并浏览受体或配体家族以识别各自家族中配体与受体之间的关系。由于局部信号系统在各种正常和患病组织中普遍存在,我们利用配体化受体组知识库来询问DNA微阵列数据集,以对潜在的旁分泌/自分泌信号系统进行全基因组分析。除了基于预先计算的DNA微阵列数据查看配体-受体共表达外,用户还可以提交自己的微阵列数据,以在线进行全基因组搜索,寻找假定的旁分泌/自分泌信号系统。基于配体化受体组对转录组数据进行研究,能够在以前未表征的组织或发育阶段发现已知配体-受体对的旁分泌/自分泌信号传导。目前对配体-受体对的注释还识别出了某些家族中没有已知相互作用伙伴的孤儿受体和配体。由于同一家族内的激素配体通常与旁系同源受体相互作用,这种基因组方法也有助于孤儿受体和配体的匹配。可通过http://receptome.stanford.edu访问配体化受体组。

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