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首页> 外文期刊>Journal of Bioinformatics and Computational Biology >Identification of inflammatory bowel disease-related proteins using a reverse k-nearest neighbor search
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Identification of inflammatory bowel disease-related proteins using a reverse k-nearest neighbor search

机译：使用反向k近邻搜索识别与炎症性肠疾病相关的蛋白

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摘要

Inflammatory bowel disease (IBD) is a chronic disease whose incidence and prevalence increase every year; however, the pathogenesis of IBD is still unclear. Thus, identifying IBD-related proteins is important for understanding its complex disease mechanism. Here, we propose a new and simple network-based approach using a reverse k-nearest neighbor (RkNN) search to identify novel IBD-related proteins. Protein-protein interactions (PPI) and Genome-Wide Association Studies (GWAS) were used in this study. After constructing the PPI network, the RkNN search was applied to all of the proteins to identify sets of influenced proteins among their k-nearest neighbors (kNNs). An observed protein whose influenced proteins were mostly known IBD-related proteins was statistically identified as a novel IBD-related protein. Our method outperformed a random aspect, kNN search, and centrality measures based on the network topology. A total of 39 proteins were identified as IBD-related proteins. Of these proteins, 71% were reported at least once in the literature as related to IBD. Additionally, these proteins were found over-represented in the IBD pathway and enriched in importantly functional pathways in IBD. In conclusion, the RkNN search with the statistical enrichment test is a great tool to identify IBD-related proteins to better understand its complex disease mechanism.
机译：炎性肠病（IBD）是一种慢性疾病，其发病率和患病率每年都在增加。然而，IBD的发病机制仍不清楚。因此，鉴定IBD相关蛋白对于理解其复杂的疾病机制很重要。在这里，我们提出了一种新的基于简单网络的方法，使用反向k最近邻（RkNN）搜索来识别新型IBD相关蛋白。这项研究使用了蛋白质-蛋白质相互作用（PPI）和全基因组关联研究（GWAS）。在构建了PPI网络之后，将RkNN搜索应用于所有蛋白质，以识别其k最近邻居（kNN）中受影响的蛋白质集。统计上将观察到的影响蛋白最广为人知的IBD相关蛋白称为新的IBD相关蛋白。我们的方法优于基于网络拓扑的随机方面，kNN搜索和集中度度量。总共鉴定出39种蛋白质为IBD相关蛋白质。在这些蛋白质中，有71％在文献中至少报道过一次与IBD相关的蛋白质。另外，发现这些蛋白在IBD途径中过量表达，并在IBD中重要的功能途径中富集。总之，使用统计富集测试进行RkNN搜索是识别IBD相关蛋白以更好地了解其复杂疾病机制的重要工具。

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