Bioinformatics construction of the human cell surfaceome
Bioinformatics construction of the human cell surfaceome
复制标题
DOI：
10.1073/pnas.0907939106
复制
发表时间：
2009-09-29
影响因子：
11.1
通讯作者：
de Souza, S. J.
中科院分区：
文献类型：
--
作者：
da Cunha, J. P. C.;Galante, P. A. F.;de Souza, S. J.
细胞表面蛋白是诊断和治疗干预的极好靶点。通过使用生物信息学工具，我们生成了位于人类细胞表面的3，702个跨膜蛋白（人类细胞表面组）的目录。我们探讨了人类细胞表面基因组在不同水平上的遗传多样性，包括多态性的分布，真核生物物种之间的保守性和基因表达模式。通过整合来自各种来源的表达信息，我们能够鉴定在正常组织中具有限制性表达和/或在肿瘤中具有差异表达的表面基因组基因，这是推定的肿瘤靶点的重要特征。一种高通量和高效的定量实时PCR方法被用来验证593个表面基因组基因的基础上，他们在正常和肿瘤样品中的表达模式选择。许多候选人被确定为结直肠肿瘤和胶质母细胞瘤的潜在诊断和治疗靶点。几个候选基因也被确定为编码细胞表面癌/睾丸抗原。人类细胞表面组将作为进一步研究的参考，旨在表征人类细胞表面的肿瘤靶点。
Cell surface proteins are excellent targets for diagnostic and therapeutic interventions. By using bioinformatics tools, we generated a catalog of 3,702 transmembrane proteins located at the surface of human cells (human cell surfaceome). We explored the genetic diversity of the human cell surfaceome at different levels, including the distribution of polymorphisms, conservation among eukaryotic species, and patterns of gene expression. By integrating expression information from a variety of sources, we were able to identify surfaceome genes with a restricted expression in normal tissues and/or differential expression in tumors, important characteristics for putative tumor targets. A high-throughput and efficient quantitative real-time PCR approach was used to validate 593 surfaceome genes selected on the basis of their expression pattern in normal and tumor samples. A number of candidates were identified as potential diagnostic and therapeutic targets for colorectal tumors and glioblastoma. Several candidate genes were also identified as coding for cell surface cancer/testis antigens. The human cell surfaceome will serve as a reference for further studies aimed at characterizing tumor targets at the surface of human cells.