In Silico target fishing: addressing a "Big Data" problem by ligand-based similarity rankings with data fusion.
In Silico target fishing: addressing a "Big Data" problem by ligand-based similarity rankings with data fusion.
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In Silico 目标钓鱼：通过基于配体的相似性排名和数据融合解决“大数据”问题
DOI：
10.1186/1758-2946-6-33
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发表时间：
2014
影响因子：
8.6
通讯作者：
Jiang H
中科院分区：
文献类型：
--
作者：
Liu X;Xu Y;Li S;Wang Y;Peng J;Luo C;Luo X;Zheng M;Chen K;Jiang H
基于配体的电子靶标捕捞可用于识别生物活性配体的潜在相互作用靶点，这有助于理解现有药物的多药理学和安全性概况。这种方法的基本原理是，已知的生物活性配体可以作为参考来预测新化合物的目标。我们测试了一条能够进行大规模目标捕捞和药物重新定位的管道，该管道基于简单的指纹相似度排名和数据融合。编制了一个包含533个药物相关靶点和179,807个活性配体的大型文库，其中每个靶点由其配体集定义。对于给定的查询分子，通过针对分配给每个靶标的配位体集合进行相似性搜索来生成其靶标简档，然后将利用多个参考结构的各个搜索融合到代表查询化合物的潜在靶标相互作用简档的单个排序列表中。所提出的方法通过10倍交叉验证和两次外部测试，使用DrugBank和治疗靶点数据库(TTD)的数据进行了验证。并以药物定位和药物副作用预测为例，进一步说明了该方法的应用。这些有希望的结果表明，所提出的方法不仅有助于发现混杂药物的新用途，而且还可以预测一些重要的毒性责任。随着药物相关靶标及其配体数据的快速增长和多样性，基于简单配体的靶标捕捞方法将在未来的药物设计和发现中发挥重要作用。
Ligand-based in silico target fishing can be used to identify the potential interacting target of bioactive ligands, which is useful for understanding the polypharmacology and safety profile of existing drugs. The underlying principle of the approach is that known bioactive ligands can be used as reference to predict the targets for a new compound. We tested a pipeline enabling large-scale target fishing and drug repositioning, based on simple fingerprint similarity rankings with data fusion. A large library containing 533 drug relevant targets with 179,807 active ligands was compiled, where each target was defined by its ligand set. For a given query molecule, its target profile is generated by similarity searching against the ligand sets assigned to each target, for which individual searches utilizing multiple reference structures are then fused into a single ranking list representing the potential target interaction profile of the query compound. The proposed approach was validated by 10-fold cross validation and two external tests using data from DrugBank and Therapeutic Target Database (TTD). The use of the approach was further demonstrated with some examples concerning the drug repositioning and drug side-effects prediction. The promising results suggest that the proposed method is useful for not only finding promiscuous drugs for their new usages, but also predicting some important toxic liabilities. With the rapid increasing volume and diversity of data concerning drug related targets and their ligands, the simple ligand-based target fishing approach would play an important role in assisting future drug design and discovery.
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DOI：
10.1021/ci970437z
发表时间：
1998-05-01
期刊：
JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES
影响因子：
--
作者：
Flower, DR
通讯作者：
Flower, DR
PharmMapper 服务器：使用药效团映射方法识别潜在药物靶标的网络服务器
影响因子：
14.9
作者：
Liu X;Ouyang S;Yu B;Liu Y;Huang K;Gong J;Zheng S;Li Z;Li H;Jiang H
通讯作者：
Jiang H
影响因子：
5.6
作者：
Cheng T;Li Q;Wang Y;Bryant SH
通讯作者：
Bryant SH
DOI：
10.1021/ci034231b
发表时间：
2004-05-01
期刊：
JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES
影响因子：
--
作者：
Hert, J;Willett, P;Wilton, DJ
通讯作者：
Wilton, DJ
影响因子：
64.8
作者：
通讯作者：
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