HitPickV2: a web server to predict targets of chemical compounds
HitPickV2: a web server to predict targets of chemical compounds
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DOI：
10.1093/bioinformatics/bty759
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发表时间：
2019-04-01
期刊：
影响因子：
5.8
通讯作者：
Campillos, Monica
中科院分区：
文献类型：
--
作者：
Hamad, Sabri;Adornetto, Gianluca;Campillos, Monica
新化合物的蛋白质靶点的鉴定是了解化合物的作用机制导致生物效应的必要条件。确定这些蛋白质靶点的实验方法通常是缓慢、昂贵和耗时的。最近，计算工具作为一种更便宜、更快的替代方法出现了，它可以预测大量化合物的靶标。在这里，我们提出了HitPickV2，一种基于配体的新方法，用于预测多种化合物的人类可药物蛋白靶点。对于每个查询化合物，HitPickV2预测了2739种人类可药物蛋白中的10个目标。为了实现这一目标，HitPickV2在一个巨大的化学-蛋白质相互作用区域的有限空间内识别出最接近的、结构相似的化合物，直到发现10个不同的蛋白质目标。然后，HitPickV2根据该空间中目标的三个参数对这10个目标进行评分：查询与与目标相互作用的最相似化合物之间的谷本系数（Tc），考虑Tc和拉普拉斯修正朴素贝叶斯目标模型分数的目标等级，以及HitPickV2中引入的新参数，即与每个目标相互作用的化合物的数量（发生）。我们展示了HitPickV2在交叉验证和外部数据集中的性能结果。可用性和实施HitPickV2可在www.hitpickv2.com.Supplementary information获得补充数据可在Bioinformatics在线获得。
Motivation The identification of protein targets of novel compounds is essential to understand compounds' mechanisms of action leading to biological effects. Experimental methods to determine these protein targets are usually slow, costly and time consuming. Computational tools have recently emerged as cheaper and faster alternatives that allow the prediction of targets for a large number of compounds.Results Here, we present HitPickV2, a novel ligand-based approach for the prediction of human druggable protein targets of multiple compounds. For each query compound, HitPickV2 predicts up to 10 targets out of 2739 human druggable proteins. To that aim, HitPickV2 identifies the closest, structurally similar compounds in a restricted space within a vast chemical-protein interaction area, until 10 distinct protein targets are found. Then, HitPickV2 scores these 10 targets based on three parameters of the targets in such space: the Tanimoto coefficient (Tc) between the query and the most similar compound interacting with the target, a target rank that considers Tc and Laplacian-modified naive Bayesian target models scores and a novel parameter introduced in HitPickV2, the number of compounds interacting with each target (occur). We present the performance results of HitPickV2 in cross-validation as well as in an external dataset.Availability and implementation HitPickV2 is available in www.hitpickv2.com.Supplementary informationSupplementary data are available at Bioinformatics online.