title: DRABAL: novel method to mine large high-throughput screening assays using Bayesian active learning.
abstract: BACKGROUND
  Mining high-throughput screening (HTS) assays is key for enhancing decisions in the area of drug repositioning and drug discovery. However, many challenges are encountered in the process of developing suitable and accurate methods for extracting useful information from these assays. Virtual screening and a wide variety of databases, methods and solutions proposed to-date, did not completely overcome these challenges. This study is based on a multi-label classification (MLC) technique for modeling correlations between several HTS assays, meaning that a single prediction represents a subset of assigned correlated labels instead of one label. Thus, the devised method provides an increased probability for more accurate predictions of compounds that were not tested in particular assays.
  
  
  RESULTS
  Here we present DRABAL, a novel MLC solution that incorporates structure learning of a Bayesian network as a step to model dependency between the HTS assays. In this study, DRABAL was used to process more than 1.4 million interactions of over 400,000 compounds and analyze the existing relationships between five large HTS assays from the PubChem BioAssay Database. Compared to different MLC methods, DRABAL significantly improves the F1Score by about 22%, on average. We further illustrated usefulness and utility of DRABAL through screening FDA approved drugs and reported ones that have a high probability to interact with several targets, thus enabling drug-multi-target repositioning. Specifically DRABAL suggests the Thiabendazole drug as a common activator of the NCP1 and Rab-9A proteins, both of which are designed to identify treatment modalities for the Niemann-Pick type C disease.
  
  
  CONCLUSIONS
  We developed a novel MLC solution based on a Bayesian active learning framework to overcome the challenge of lacking fully labeled training data and exploit actual dependencies between the HTS assays. The solution is motivated by the need to model dependencies between existing experimental confirmatory HTS assays and improve prediction performance. We have pursued extensive experiments over several HTS assays and have shown the advantages of DRABAL. The datasets and programs can be downloaded from https://figshare.com/articles/DRABAL/3309562.Graphical abstract.
authors.affiliation: Computational Bioscience Research Center (CBRC), King Abdullah University of Science and Technology (KAUST), Thuwal, 23955-6900 Saudi Arabia.
authors.forename: Othman
authors.initials: O
authors.lastname: Soufan
authors.affiliation: Computational Bioscience Research Center (CBRC), King Abdullah University of Science and Technology (KAUST), Thuwal, 23955-6900 Saudi Arabia.
authors.forename: Wail
authors.initials: W
authors.lastname: Ba-Alawi
authors.affiliation: Computational Bioscience Research Center (CBRC), King Abdullah University of Science and Technology (KAUST), Thuwal, 23955-6900 Saudi Arabia.
authors.forename: Moataz
authors.initials: M
authors.lastname: Afeef
authors.affiliation: Computational Bioscience Research Center (CBRC), King Abdullah University of Science and Technology (KAUST), Thuwal, 23955-6900 Saudi Arabia.
authors.forename: Magbubah
authors.initials: M
authors.lastname: Essack
authors.affiliation: Infocloud Group, Computer, Electrical and Mathematical Sciences and Engineering Division (CEMSE), King Abdullah University of Science and Technology (KAUST), Thuwal, 23955-6900 Saudi Arabia.
authors.forename: Panos
authors.initials: P
authors.lastname: Kalnis
authors.affiliation: Computational Bioscience Research Center (CBRC), King Abdullah University of Science and Technology (KAUST), Thuwal, 23955-6900 Saudi Arabia.
authors.forename: Vladimir B
authors.identifier: 0000-0001-5435-4750
authors.initials: VB
authors.lastname: Bajic