IEEE/ACM Trans Comput Biol Bioinform. 2020 Nov-Dec;17(6):2155-2161. doi: 10.1109/TCBB.2019.2938512. Epub 2020 Dec 8.
A fundamental topic in network medicine is disease genes prioritization. The underlying hypothesis is that disease genes are organized as modules confined within the interactome. Here, we propose a novel algorithm called DiaBLE (DIAMOnD Background Local Expansion) which is a modified version of DIAMOnD, a successful algorithm based on the concept of connectivity significance. Instead of taking the whole interactome as the background model, DiaBLE considers as gene universe the smallest local expansion of the current seeds set at each iteration step. We show that DiaBLE significantly increases the overall DIAMOnD ranking quality of genes prioritization both in terms of cross-validation and biological consistency. Here, we focus on the two algorithms only since a comparative analysis among gene prioritization methods is beyond the scope of this study. Finally, we briefly discuss the improvement of biological insight provided by DiaBLE for two cancers (head and neck squamous cell carcinoma and kidney renal clear cell carcinoma).
网络医学中的一个基本课题是疾病基因优先级排序。其基本假设是疾病基因作为模块组织在相互作用组内。在这里，我们提出了一种名为 DiaBLE（DIAMOnD 背景局部扩展）的新算法，它是基于连接显著性概念的成功算法 DIAMOnD 的一种修改版本。DiaBLE 没有将整个相互作用组作为背景模型，而是在每次迭代步骤中将当前种子集的最小局部扩展视为基因宇宙。我们表明，DiaBLE 显著提高了基因优先级排序的整体 DIAMOnD 排名质量，无论是在交叉验证还是在生物学一致性方面。在这里，我们仅关注这两个算法，因为基因优先级排序方法的比较分析超出了本研究的范围。最后，我们简要讨论了 DiaBLE 为两种癌症（头颈部鳞状细胞癌和肾透明细胞癌）提供的生物学见解的改进。
