Jeffries Clark, Perkins Diana O, Jarstfer Michael
Renaissance Computing Institute and School of Pharmacy, Campus Box 7360, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7360, USA.
J Theor Biol. 2006 Jul 21;241(2):205-15. doi: 10.1016/j.jtbi.2005.11.027. Epub 2006 Jan 5.
Recent discovery of gene expression mechanisms has propelled molecular genetics to a state of rapid development, a state likely to persist due to continuing advances in understanding control systems of fundamental cellular processes. An algorithm for that advancement starts in this paper with a gene of interest and a characteristic function of that gene. The set of all genes with counteracting function is identified by pathway searches. Also associated with the first gene is the set of the genes which byproducts of its transcription might downregulate, identified relative to searches involving sequence alignments. Our focus is the intersection of the counteracting gene set and the downregulated gene set. The result is hypothesis generation. Examples of and predictions from this approach are given in the context of apoptosis. Also discussed is application of the algorithm to rational drug design from a new development platform.
基因表达机制的最新发现推动分子遗传学进入快速发展阶段,由于在理解基本细胞过程控制系统方面的持续进展,这种状态可能会持续下去。本文从一个感兴趣的基因及其特征功能出发,提出了一种推进这一发展的算法。通过通路搜索来识别具有拮抗功能的所有基因集。与第一个基因相关的还有一组基因,其转录副产物可能会下调这些基因,这是相对于涉及序列比对的搜索来确定的。我们关注的是拮抗基因集和下调基因集的交集。结果就是产生假设。在细胞凋亡的背景下给出了这种方法的示例和预测。还讨论了该算法在基于新开发平台进行合理药物设计中的应用。