In silico data filtering to identify new angiogenesis targets from a large in vitro gene profiling data set
In silico data filtering to identify new angiogenesis targets from a large in vitro gene profiling data set
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DOI：
10.1152/physiolgenomics.00035.2002
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发表时间：
2002-07-12
影响因子：
4.6
通讯作者：
Williams, PM
中科院分区：
文献类型：
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作者：
Gerritsen, ME;Soriano, R;Williams, PM
本研究的目的是使用来自明确定义的细胞培养模型的基因表达数据，结合来自人类患病组织诊断样本的表达数据，来识别潜在的治疗靶点和疾病标志物。使用Affyssin寡核苷酸阵列技术，我们确定了一个共同的基因上调过程中的内皮细胞形态形成tubelike结构在三个体外模型的血管生成。使用严格的数据选择标准来鉴定超过1，000个基因的列表，这些基因的表达在4、8、24、40或50 h时比基线增加两倍以上。为了进一步完善和优先考虑这个列表，我们使用标准的生物信息学算法来识别潜在的跨膜和分泌蛋白。然后，我们将这个基因集与结肠肿瘤与正常结肠中上调的基因重叠，得到了与我们的内皮细胞列表相同的128个基因的子集。我们从该列表中删除了在6种不同结肠肿瘤细胞系中表达的基因，得到了24个推定的血管特异性血管生成相关基因的列表。三个基因，gp 34，斯钙素-1（STC-1），和GA 733 -1，在结肠肿瘤中的表达水平为正常粘膜的10倍或更多。我们通过原位杂交验证了这些基因之一STC-1的血管特异性表达。联合收割机体外和体内数据集的能力应该允许人们识别各种肿瘤、慢性炎症和其他疾病中推定的血管生成靶基因，其中血管生成的治疗操作是理想的治疗方式。
The objective of this study was to use gene expression data from well-defined cell culture models, in combination with expression data from diagnostic samples of human diseased tissues, to identify potential therapeutic targets and markers of disease. Using Affymetrix oligonucleotide array technology, we identified a common profile of genes upregulated during endothelial morphogenesis into tubelike structures in three in vitro models of angiogenesis. Rigorous data selection criteria were used to identify a list of over 1,000 genes whose expression was increased more than twofold over baseline at either 4, 8, 24, 40 or 50 h. To further refine and prioritize this list, we used standard bioinformatic algorithms to identify potential transmembrane and secreted proteins. We then overlapped this gene set with genes upregulated in colon tumors vs. normal colon, resulting in a subset of 128 genes in common with our endothelial list. We removed from this list those genes expressed in 6 different colon tumor lines, resulting in a list of 24 putative, vascular-specific angiogenesis-associated genes. Three genes, gp34, stanniocalcin-1 (STC-1), and GA733-1, were expressed at levels 10-fold or more in colon tumors compared with normal mucosa. We validated the vascular-specific expression of one of these genes, STC-1, by in situ hybridization. The ability to combine in vitro and in vivo data sets should permit one to identify putative angiogenesis target genes in various tumors, chronic inflammation, and other disorders where therapeutic manipulation of angiogenesis is a desirable treatment modality.