title: In Silico target fishing: addressing a "Big Data" problem by ligand-based similarity rankings with data fusion.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China.
authors: Xian
authors: X
authors: Liu
authors: Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China.
authors: Yuan
authors: Y
authors: Xu
authors: Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China.
authors: Shanshan
authors: S
authors: Li
authors: Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China.
authors: Yulan
authors: Y
authors: Wang
authors: Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China.
authors: Jianlong
authors: J
authors: Peng
authors: Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China.
authors: Cheng
authors: C
authors: Luo
authors: Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China.
authors: Xiaomin
authors: X
authors: Luo
authors: Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China.
authors: Mingyue
authors: M
authors: Zheng
authors: Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China ; School of Life Science and Technology, ShanghaiTech University, Shanghai 200031, China.
authors: Kaixian
authors: K
authors: Chen
authors: Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China ; School of Life Science and Technology, ShanghaiTech University, Shanghai 200031, China.
authors: Hualiang
authors: H
authors: Jiang
keywords: Big data; Data fusion; Molecular fingerprints; Similarity searching; Target fishing