Abstract:
Progress in biology has generated numerous lists of genes that share some property. But, advancing from these lists of genes to understanding their roles is slow and unsystematic. Here we use RNA silencing in C. elegans to illustrate an approach for prioritizing genes for detailed study given limited resources. The partially subjective relationships between genes forged by both deduced functional relatedness and biased progress in the field was captured as mutual information and used to cluster genes that were frequently identified yet remain understudied. Studied genes in these clusters suggest regulatory links connecting RNA silencing with other processes like the cell cycle. Many proteins encoded by the understudied genes are predicted to physically interact with known regulators of RNA silencing. These predicted influencers of RNA-regulated expression could be used for feedback regulation, which is essential for the homeostasis observed in all living systems. Thus, among the gene products altered when a process is perturbed are regulators of that process, providing a way to use RNA sequencing to identify candidate protein-protein interactions. Together, the analysis of perturbed transcripts and potential interactions of the proteins they encode could help prioritize candidate regulators of any process.
摘要:
生物学的进步已经产生了许多共享某些属性的基因列表。但是,从一个过程中一组基因的最初含义到理解它们在这个过程中的作用是缓慢而不系统的。在这里,我们使用C.elegans中的RNA沉默来说明一种通用方法,用于比较一个领域积累的数据列表,以优先考虑资源有限的详细研究基因。基因的功能相关性和该领域的偏向性进展所伪造的基因之间的部分主观关系被捕获为历史互信息(HMI),并用作聚类基因的定量度量。这些簇表明了将RNA沉默与细胞周期等其他过程联系起来的调节联系,并鉴定了未研究的可用于感知扰动或介导反馈抑制的受调节基因。