Genomic Basis of Biochemical Network Topology

描述(由申请人提供)： 生化网络是由同源和非同源蛋白质组成的网络。在根据组学结果生成的网络模型中检测到“小世界”拓扑--通常是无尺度的，其中少数中枢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导出这种拓扑--仍然是一个悬而未决的问题。这一提议发起了一项尝试，试图在基因组序列中为这种拓扑结构找到立足点。重点是平行蛋白的功能多样化和网络中平行路径的形成，其中固有无序蛋白(IDP)片段被假设扮演着突出的角色。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，类似的蛋白质在功能特异性上存在差异，形成了平行的通路。蛋白质组序列将被聚集到家族中，每个蛋白质被分配一个数字家族ID。然后，生化网络模型将被用这种数字格式注释。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并行路径。2：无序区在生化网络拓扑结构中的作用。据推测，内毒素对同源蛋白的功能多样化是至关重要的。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相结合的方式进行验证。3：无标度分布和多细胞。指数分布的指数常数因物种不同而不同。为了解释从单细胞物种到多细胞物种的这种差异，将为特定的组织/细胞类型确定这一常数。无序区在多细胞物种中平行蛋白功能多样化中的作用也将被调查。

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.