Open Peer Review Discuss this article (0) Comments METHOD ARTICLE Virtual-screening workflow tutorials and prospective results from the Teach-Discover-Treat competition 2014 against malaria [version 2; referees: 3 approved] Sereina Riniker , Gregory A. Landrum , Floriane Montanari , Santiago D. Villalba , Julie Maier , Johanna M. Jansen , W. Patrick Walters , Anang A. Shelat 5 Laboratory of Physical Chemistry, ETH Zürich, Zürich, Switzerland T5 Informatics GmbH, Basel, Switzerland Pharmacoinformatics Research Group, Department of Pharmaceutical Chemistry, University of Vienna, Vienna, Austria IMP - Research Institute of Molecular Pathology, Vienna Biocenter, Vienna, Austria Department of Chemical Biology & Therapeutics, St. Jude Children's Research Hospital, Memphis, TN, USA Department of Global Discovery Chemistry, Novartis Institutes for BioMedical Research, Emeryville, CA, USA Relay Therapeutics, Cambridge, MA, USA Abstract The first challenge in the 2014 competition launched by the Teach-Discover-Treat (TDT) initiative asked for the development of a tutorial for ligand-based virtual screening, based on data from a primary phenotypic high-throughput screen (HTS) against malaria. The resulting Workflows were applied to select compounds from a commercial database, and a subset of those were purchased and tested experimentally for anti-malaria activity. Here, we present the two most successful Workflows, both using machine-learning approaches, and report the results for the 114 compounds tested in the follow-up screen. Excluding the two known anti-malarials quinidine and amodiaquine and 31 compounds already present in the primary HTS, a high hit rate of 57% was found. Keywords Malaria, neglected diseases, virtual screening, machine learning This article is included in the Machine learning: life collection. sciences 1 2 3 4 5 6 7 5 1 2 3 4 5 6 7 Referee Status: Invited Referees version 2 published 19 Feb 2018 version 1 published 17 Jul 2017 1 2 3 report report report , University of David Ryan Koes Pittsburgh, USA 1 , Eli Lilly Matthew P. Baumgartner and Company, UK 2 , Charité - Andrea Volkamer Universitätsmedizin, Germany 3 17 Jul 2017, :1136 ( First published: 6 ) https://doi.org/10.12688/f1000research.11905.1 19 Feb 2018, :1136 ( Latest published: 6 ) https://doi.org/10.12688/f1000research.11905.2 v2 Page 1 of 24 F1000Research 2018, 6:1136 Last updated: 29 OCT 2018