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      SwissTargetPrediction: updated data and new features for efficient prediction of protein targets of small molecules

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          Abstract

          SwissTargetPrediction is a web tool, on-line since 2014, that aims to predict the most probable protein targets of small molecules. Predictions are based on the similarity principle, through reverse screening. Here, we describe the 2019 version, which represents a major update in terms of underlying data, backend and web interface. The bioactivity data were updated, the model retrained and similarity thresholds redefined. In the new version, the predictions are performed by searching for similar molecules, in 2D and 3D, within a larger collection of 376 342 compounds known to be experimentally active on an extended set of 3068 macromolecular targets. An efficient backend implementation allows to speed up the process that returns results for a druglike molecule on human proteins in 15–20 s. The refreshed web interface enhances user experience with new features for easy input and improved analysis. Interoperability capacity enables straightforward submission of any input or output molecule to other on-line computer-aided drug design tools, developed by the SIB Swiss Institute of Bioinformatics. High levels of predictive performance were maintained despite more extended biological and chemical spaces to be explored, e.g. achieving at least one correct human target in the top 15 predictions for >70% of external compounds. The new SwissTargetPrediction is available free of charge ( www.swisstargetprediction.ch).

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          Most cited references12

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          Similarity-based machine learning methods for predicting drug-target interactions: a brief review.

          Computationally predicting drug-target interactions is useful to select possible drug (or target) candidates for further biochemical verification. We focus on machine learning-based approaches, particularly similarity-based methods that use drug and target similarities, which show relationships among drugs and those among targets, respectively. These two similarities represent two emerging concepts, the chemical space and the genomic space. Typically, the methods combine these two types of similarities to generate models for predicting new drug-target interactions. This process is also closely related to a lot of work in pharmacogenomics or chemical biology that attempt to understand the relationships between the chemical and genomic spaces. This background makes the similarity-based approaches attractive and promising. This article reviews the similarity-based machine learning methods for predicting drug-target interactions, which are state-of-the-art and have aroused great interest in bioinformatics. We describe each of these methods briefly, and empirically compare these methods under a uniform experimental setting to explore their advantages and limitations.
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            SwissSimilarity: A Web Tool for Low to Ultra High Throughput Ligand-Based Virtual Screening.

            SwissSimilarity is a new web tool for rapid ligand-based virtual screening of small to unprecedented ultralarge libraries of small molecules. Screenable compounds include drugs, bioactive and commercial molecules, as well as 205 million of virtual compounds readily synthesizable from commercially available synthetic reagents. Predictions can be carried out on-the-fly using six different screening approaches, including 2D molecular fingerprints as well as superpositional and fast nonsuperpositional 3D similarity methodologies. SwissSimilarity is part of a large initiative of the SIB Swiss Institute of Bioinformatics to provide online tools for computer-aided drug design, such as SwissDock, SwissBioisostere or SwissTargetPrediction with which it can interoperate, and is linked to other well-established online tools and databases. User interface and backend have been designed for simplicity and ease of use, to provide proficient virtual screening capabilities to specialists and nonexperts in the field. SwissSimilarity is accessible free of charge or login at http://www.swisssimilarity.ch .
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              In silico methods to address polypharmacology: current status, applications and future perspectives.

              Polypharmacology, a new paradigm in drug discovery that focuses on multi-target drugs (MTDs), has potential application for drug repurposing, the process of finding new uses for existing approved drugs, prediction of off-target toxicities and rational design of MTDs. In this scenario, computational strategies have demonstrated great potential in predicting polypharmacology and in facilitating drug repurposing. Here, we provide a comprehensive overview of various computational approaches that enable the prediction and analysis of in vitro and in vivo drug-response phenotypes and outline their potential for drug discovery. We give an outlook on the latest advances in rational design of MTDs and discuss possible future directions of algorithm development in this field.
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                Author and article information

                Journal
                Nucleic Acids Res
                Nucleic Acids Res
                nar
                Nucleic Acids Research
                Oxford University Press
                0305-1048
                1362-4962
                02 July 2019
                20 May 2019
                20 May 2019
                : 47
                : W1
                : W357-W364
                Affiliations
                [1 ]Molecular Modeling Group, SIB Swiss Institute of Bioinformatics, University of Lausanne, Quartier UNIL-Sorge, Bâtiment Amphipôle, CH-1015 Lausanne, Switzerland
                [2 ]Department of Oncology, University Hospital of Lausanne, Ludwig Cancer Research – Lausanne Branch, CH-1011 Lausanne, Switzerland
                [3 ]Department of Fundamental Oncology, University of Lausanne, Ludwig Cancer Research – Lausanne Branch, Route de la Corniche 9A, CH-1066 Epalinges, Switzerland
                Author notes
                To whom correspondence should be addressed. Vincent Zoete. Tel: +41 21 692 59 07; Email: vincent.zoete@ 123456unil.ch
                Correspondence may also be addressed to Olivier Michielin. Tel: +41 21 692 40 53; Email: olivier.michielin@ 123456unil.ch
                Author information
                http://orcid.org/0000-0002-0074-7601
                Article
                gkz382
                10.1093/nar/gkz382
                6602486
                31106366
                c7880c0d-a924-446b-8a27-d3866e11d7ae
                © The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@ 123456oup.com

                History
                : 01 May 2019
                : 26 April 2019
                : 11 February 2019
                Page count
                Pages: 8
                Funding
                Funded by: Swiss Institute of Bioinformatics 10.13039/501100007353
                Categories
                Web Server Issue

                Genetics
                Genetics

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