Towards integrative annotation of the cell-type specific gene functional and signaling map in vascular endothelial cells
Towards integrative annotation of the cell-type specific gene functional and signaling map in vascular endothelial cells
复制标题
血管内皮细胞细胞类型特异性基因功能和信号传导图谱的综合注释
DOI：
10.1039/c2mb25065a
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发表时间：
2012-01-01
影响因子：
--
通讯作者：
Li, Shao
中科院分区：
文献类型：
--
作者：
Gu, Jin;Li, Shao
血管内皮细胞（Vascular endothelial cells, VECs）是构成血管内表面的细胞，在许多生理和病理过程中起着重要作用。VECs暴露于由循环系统传递的各种微环境刺激中。系统地破译VECs对复杂微环境刺激的基因功能和信号通路是血管生物学的基本任务之一。目前，一些数据库的目标是全基因组注释基因功能和信号通路，但大多数数据库对细胞类型特异性信息的考虑有限。而且，目前的注释只提供了参与不同信号通路的核心基因，缺乏对外围信号分子或信号交叉对话的注释。为了快速构建VECs的全基因组基因功能和信号图谱，我们通过整合细胞类型特异性基因表达谱、全基因组蛋白-蛋白相互作用（PPI）网络、基因本体（GO）注释和microRNA （miRNA）靶基因信息，开发了一个基于网络的注释系统（Nanno）。利用该系统，我们成功地重新标注了参与几种基本细胞功能的基因，并以细胞类型特异性的方式鉴定了VECs中不同刺激下的信号通路。Nanno可以恢复许多未包含在GO注释中的重要基因。一些典型的信号通路和mirna被预测参与VECs的炎症和血管生成信号。这些注解表明两种条件下的细胞周期调节可能存在交叉对话。
Vascular endothelial cells (VECs), which form the inner surface of blood vessels, play essential roles in many physiological and pathological processes. VECs are exposed to various micro-environmental stimuli delivered by the circulatory systems. Systematically deciphering the gene functions and signaling circuits in VECs responsive to the complex micro-environmental stimuli is one of the fundamental tasks in vascular biology. Currently, several databases aim at genome-widely annotating the gene functions and signaling circuits, but most of them take limited consideration on the cell-type specific information. And also, current annotations only provide the core genes involved in different signaling circuits, lacking the annotations on the peripheral signaling molecules or the signaling cross-talks. To quickly construct the genome-wide gene functional and signaling map in VECs, we developed a Network-based annotating system (Nanno) by integrating cell-type specific gene expression profiles, genome-wide protein-protein interaction (PPI) networks, Gene Ontology (GO) annotations and microRNA (miRNA) target gene information. Using this system, we successfully re-annotated the genes involved in several essential cellular functions and also identified the signaling circuits under different stimuli in VECs in a cell-type specific manner. Many important genes, which are not included in GO annotations, can be recovered by Nanno. And several canonical signaling pathways and miRNAs are predicted to involve in the inflammatory and angiogenic signaling in VECs. The annotations suggest that there may exist cross-talks in cell cycle regulation between the two conditions.