Department of Complex and Intelligent Systems, Future University Hakodate, Hokkaido, Japan.
PLoS One. 2012;7(1):e30028. doi: 10.1371/journal.pone.0030028. Epub 2012 Jan 18.
Recent studies have highlighted the importance of interconnectivity in a large range of molecular and human disease-related systems. Network medicine has emerged as a new paradigm to deal with complex diseases. Connections between protein complexes and key diseases have been suggested for decades. However, it was not until recently that protein complexes were identified and classified in sufficient amounts to carry out a large-scale analysis of the human protein complex system. We here present the first systematic and comprehensive set of relationships between protein complexes and associated drugs and analyzed their topological features. The network structure is characterized by a high modularity, both in the bipartite graph and in its projections, indicating that its topology is highly distinct from a random network and that it contains a rich and heterogeneous internal modular structure. To unravel the relationships between modules of protein complexes, drugs and diseases, we investigated in depth the origins of this modular structure in examples of particular diseases. This analysis unveils new associations between diseases and protein complexes and highlights the potential role of polypharmacological drugs, which target multiple cellular functions to combat complex diseases driven by gain-of-function mutations.
最近的研究强调了在广泛的分子和人类疾病相关系统中相互联系的重要性。网络医学已经成为一种处理复杂疾病的新范例。几十年来，人们一直认为蛋白质复合物与关键疾病之间存在联系。然而，直到最近，才鉴定和分类了足够数量的蛋白质复合物，以对人类蛋白质复合物系统进行大规模分析。我们在这里首次提出了蛋白质复合物与相关药物之间的系统而全面的关系，并分析了它们的拓扑特征。网络结构的特点是双曲图及其投影的高模块性，这表明其拓扑结构与随机网络有很大的不同，并且包含丰富多样的内部模块结构。为了揭示蛋白质复合物、药物和疾病之间的模块关系，我们深入研究了特定疾病示例中这种模块结构的起源。这种分析揭示了疾病和蛋白质复合物之间的新关联，并强调了多靶药物的潜在作用，这些药物针对多种细胞功能，以对抗由功能获得性突变驱动的复杂疾病。
