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

Matching receptome genes with their ligands for surveying paracrine/autocrine signaling systems
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DOI:
10.1210/me.2007-0087
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发表时间:
2007-08-01
影响因子:
--
通讯作者:
Hsueh, Aaron J. W.
Hsueh, Aaron J. W.
中科院分区:
医学2区
文献类型:
--
作者:
Ben-Shlomo, Izhar;Rauch, Rami;Hsueh, Aaron J. W.

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对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。我们扩展了之前在人质膜受体组数据库中注释大多数人质膜受体的努力,通过调查已发表的文献将同源配体与单个受体进行匹配。在更新的在线数据库中,我们称之为“配体受体组”,用户可以搜索单个配体或受体,以揭示其配对伙伴,并浏览受体或配体家族,以确定其各自家族中配体和受体之间的关系。由于局部信号系统在不同的正常和患病组织中普遍存在,我们使用配体受体组知识库来询问DNA微阵列数据集,以进行潜在的旁分泌/自分泌信号系统的全基因组分析。除了查看基于预先计算的DNA微阵列数据的配体-受体共表达外,用户还可以提交自己的微阵列数据,以进行在线全基因组搜索,寻找假定的旁分泌/自分泌信号系统。基于配体受体组的转录组数据的调查允许在先前未表征的组织或发育阶段中发现已知配体-受体对的旁分泌/自分泌信号传导。配体-受体对的本注释还鉴定了在选择的家族中没有已知相互作用伴侣的孤儿受体和配体。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,因此这种基因组方法也可以促进孤儿受体和配体的匹配。配体化的受体组可在http://receptome.stanford.edu上获得。
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.