Genomic Basis of Biochemical Network Topology

描述（由申请人提供）： 生化网络是同源和非同源蛋白质的网格。在组学结果生成的网络模型中检测到“小世界”拓扑（通常是无标度的，其中少量的中心节点显示出极高的连接性）。无标度拓扑的基因组基础——如何从基因组序列推导出这种拓扑——仍然是一个悬而未决的问题。该提案发起了在基因组序列中寻找这种拓扑结构基础的尝试。重点是旁系同源蛋白的功能多样化以及网络中平行通路的形成，其中内在无序蛋白（IDP）片段被假设发挥着重要作用。我们的具体目标如下。图 1：量化生化网络中的平行路径。我们的初步研究表明旁系同源蛋白在功能特异性方面存在差异，形成平行途径。蛋白质组序列将被聚类成家族，并且每个蛋白质被分配一个数字家族 ID。然后，生化网络模型将用这种数字格式进行注释。随后，可以通过分析这些数字 ID 的组合模式来可视化和量化平行路径。图2：无序区域在生化网络拓扑中的作用。据推测，IDP 对于旁系同源蛋白的功能多样化至关重要。这一假设将通过全基因组 IDP 分析、比较基因组分析以及实验验证的结合来检验。 3：无标度分布和多细胞性。幂律分布的指数常数因物种而异。将为特定组织/细胞类型确定该常数，以解释从单细胞物种到多细胞物种的这种变化。还将研究无序区域在多细胞物种中旁系同源蛋白功能多样化中的作用。

DESCRIPTION (provided by applicant): Biochemical networks are meshes of homologous and non-homologous proteins. The "small world" topology - often scale free and in which a small number of hub nodes display extraordinarily high connectivity - is detected in the network models generated from omics results. Genomic basis of the scale-free topology - how to deduce this topology from genomic sequences - remains an open question. This proposal initiates an attempt to find a footing for this topology in genomic sequences. The focus is functional diversification of paralogous proteins and the formation of parallel pathways in the networks, in which the intrinsically disordered protein (IDP) segments is hypothesized to play preeminent roles. Our specific aims are as follows. 1: Quantifying parallel pathways in biochemical networks. Our preliminary studies suggest paralogous proteins diverge in their functional specificity to form parallel pathways. The proteome sequences would be clustered into families and each protein assigned to a numerical family ID. Biochemical network models would then be annotated with this numerical format. Subsequently, parallel pathways can be visualized and quantified by analysis combinatorial patterns of these numerical IDs. 2: Roles of disordered regions in the topology of biochemical networks. It is hypothesized that IDPs are crucial for functional diversification of paralogous proteins. This hypothesis will be tested by a combination of genome wide IDP analysis, comparative genomic analysis as well as experimental verification. 3: Scale-free distribution and multi-cellularity. The exponent constant in power-law distribution varies across species. This constant would be determined for specific tissue/cell types in order to explain this variation from single cell species to multi-cellular species. The roles of disordered regions in functional diversification of paralogous proteins in multi-cellular species would also be investigated.