Department of Surgery, University of Pisa, Pisa, Italy.
J Periodontol. 2009 Dec;80(12):1998-2009. doi: 10.1902/jop.2009.090290.
Tentative bioinformatic predictions were performed to comprehend the complexity of the gene interaction networks of the T lymphocyte cell cycle and of human periodontitis. This study aims to identify and rank genes involved in osseous augmentation or bone remodeling to obtain groups with more numerous predicted associations called the leader gene clusters.
An iterative search (consisting of a consecutive expansion-filtering loop) was performed for which only genes involved in a specific process were identified. For each gene, predicted associations with all other involved genes were obtained from a Web-available database (Search Tool for the Retrieval of Interacting Genes/Proteins) and the weighted number of links (WNL), given by the sum of only high-confidence predicted associations (results with a score > or =0.9), allowing gene ranking. Genes belonging to higher clustering classes were identified.
A total of 161 genes potentially involved in bone-volume augmentation and 128 genes connected with the bone-remodeling phenomenon were identified. For the bone-volume augmentation process, only one gene belonged to the leader gene group, whereas six other genes were classified as cluster B genes; for the bone-remodeling phenomenon, three leader genes were identified, whereas six other genes formed the cluster B group. No one gene belonged to leader gene clusters of both processes, whereas one gene of each higher cluster group belonged to the immediately lower cluster of the opposite process. Only three genes of the higher clusters were experimentally involved in both analyses.
A de novo identification was performed based on the data mining of leader genes involved in bone-volume augmentation or bone remodeling to acquire primeval information about their molecular basis and to plan future ad hoc targeted experiments. For several genes of the upper clusters, an active role in the bone processes was already known, but the present analysis suggested that they play a major role in the analyzed phenomena. The role of the transcription factors as leader genes and the numerous orphan genes (genes with WNL = 0) recovered probably attest to a lack of information regarding these processes, which could be further clarified through specific DNA microarray experiments.
为了理解 T 淋巴细胞细胞周期和人类牙周炎的基因相互作用网络的复杂性，我们进行了初步的生物信息学预测。本研究旨在识别和对参与骨质增加或骨重塑的基因进行排序，以获得具有更多预测关联的基因群，称为“先导基因簇”。
我们进行了迭代搜索（由连续的扩展-过滤循环组成），仅识别特定过程中涉及的基因。对于每个基因，从一个可在线获取的数据库（Search Tool for the Retrieval of Interacting Genes/Proteins）获取与所有其他涉及基因的预测关联，并获得加权链接数（WNL），WNL 是仅高置信度预测关联（评分>或=0.9 的结果）的总和，这允许对基因进行排序。确定属于较高聚类类别的基因。
总共确定了 161 个可能参与骨体积增加的基因和 128 个与骨重塑现象相关的基因。对于骨体积增加过程，只有一个基因属于先导基因群，而另外六个基因被归类为 B 基因群；对于骨重塑现象，鉴定出三个先导基因，而另外六个基因形成 B 基因群。没有一个基因属于两个过程的先导基因群，而每个过程的较低聚类群中都有一个基因。只有三个较高聚类群的基因参与了这两个分析。
基于参与骨体积增加或骨重塑的先导基因的数据挖掘，进行了从头鉴定，以获取其分子基础的原始信息，并计划未来进行特定的靶向实验。对于上聚类群中的几个基因，已知其在骨过程中发挥积极作用，但本分析表明它们在分析的现象中起主要作用。转录因子作为先导基因和许多孤儿基因（WNL=0 的基因）的出现可能表明这些过程缺乏信息，这些信息可以通过特定的 DNA 微阵列实验进一步澄清。
