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状结构。从组学结果生成的网络模型中可以检测到“小世界”拓扑——通常是无比例的，其中少数集线器节点显示出极高的连通性。无标度拓扑的基因组基础-如何从基因组序列中推断出这种拓扑-仍然是一个悬而未决的问题。这一建议开启了在基因组序列中为这种拓扑结构寻找立足点的尝试。重点是同源蛋白的功能多样化和网络中平行通路的形成，其中内在无序蛋白（IDP）片段被假设起着重要作用。我们的具体目标如下。1：量化生化网络中的平行通路。我们的初步研究表明，同源蛋白在其功能特异性上存在分歧，从而形成平行通路。蛋白质组序列将被聚集成家族，每个蛋白质被分配到一个数字家族ID。然后，生化网络模型将用这种数字格式进行注释。随后，通过分析这些数值id的组合模式，可以将并行路径可视化和量化。2：无序区域在生化网络拓扑结构中的作用。据推测，IDPs对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、比较基因组分析和实验验证相结合的方法进行验证。3：无标度分布，多细胞分布。幂律分布中的指数常数在不同物种之间是不同的。为了解释这种从单细胞物种到多细胞物种的变化，这个常数将被确定为特定的组织/细胞类型。无序区在多细胞物种中同源蛋白功能多样化中的作用也将被研究。

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.