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      Machine learning applications in drug development

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          Highlights

          • Applications of sequential learning and recommender systems to pharmaceutics.

          • Review of Machine Learning methods in drug discovery, testing and repurposing.

          • Survey of available genomic data and feature selection methods for drug development.

          Abstract

          Due to the huge amount of biological and medical data available today, along with well-established machine learning algorithms, the design of largely automated drug development pipelines can now be envisioned. These pipelines may guide, or speed up, drug discovery; provide a better understanding of diseases and associated biological phenomena; help planning preclinical wet-lab experiments, and even future clinical trials. This automation of the drug development process might be key to the current issue of low productivity rate that pharmaceutical companies currently face. In this survey, we will particularly focus on two classes of methods: sequential learning and recommender systems, which are active biomedical fields of research.

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          Most cited references84

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          STRING v11: protein–protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets

          Abstract Proteins and their functional interactions form the backbone of the cellular machinery. Their connectivity network needs to be considered for the full understanding of biological phenomena, but the available information on protein–protein associations is incomplete and exhibits varying levels of annotation granularity and reliability. The STRING database aims to collect, score and integrate all publicly available sources of protein–protein interaction information, and to complement these with computational predictions. Its goal is to achieve a comprehensive and objective global network, including direct (physical) as well as indirect (functional) interactions. The latest version of STRING (11.0) more than doubles the number of organisms it covers, to 5090. The most important new feature is an option to upload entire, genome-wide datasets as input, allowing users to visualize subsets as interaction networks and to perform gene-set enrichment analysis on the entire input. For the enrichment analysis, STRING implements well-known classification systems such as Gene Ontology and KEGG, but also offers additional, new classification systems based on high-throughput text-mining as well as on a hierarchical clustering of the association network itself. The STRING resource is available online at https://string-db.org/.
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            The UK Biobank resource with deep phenotyping and genomic data

            The UK Biobank project is a prospective cohort study with deep genetic and phenotypic data collected on approximately 500,000 individuals from across the United Kingdom, aged between 40 and 69 at recruitment. The open resource is unique in its size and scope. A rich variety of phenotypic and health-related information is available on each participant, including biological measurements, lifestyle indicators, biomarkers in blood and urine, and imaging of the body and brain. Follow-up information is provided by linking health and medical records. Genome-wide genotype data have been collected on all participants, providing many opportunities for the discovery of new genetic associations and the genetic bases of complex traits. Here we describe the centralized analysis of the genetic data, including genotype quality, properties of population structure and relatedness of the genetic data, and efficient phasing and genotype imputation that increases the number of testable variants to around 96 million. Classical allelic variation at 11 human leukocyte antigen genes was imputed, resulting in the recovery of signals with known associations between human leukocyte antigen alleles and many diseases.
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              DrugBank 5.0: a major update to the DrugBank database for 2018

              Abstract DrugBank (www.drugbank.ca) is a web-enabled database containing comprehensive molecular information about drugs, their mechanisms, their interactions and their targets. First described in 2006, DrugBank has continued to evolve over the past 12 years in response to marked improvements to web standards and changing needs for drug research and development. This year’s update, DrugBank 5.0, represents the most significant upgrade to the database in more than 10 years. In many cases, existing data content has grown by 100% or more over the last update. For instance, the total number of investigational drugs in the database has grown by almost 300%, the number of drug-drug interactions has grown by nearly 600% and the number of SNP-associated drug effects has grown more than 3000%. Significant improvements have been made to the quantity, quality and consistency of drug indications, drug binding data as well as drug-drug and drug-food interactions. A great deal of brand new data have also been added to DrugBank 5.0. This includes information on the influence of hundreds of drugs on metabolite levels (pharmacometabolomics), gene expression levels (pharmacotranscriptomics) and protein expression levels (pharmacoprotoemics). New data have also been added on the status of hundreds of new drug clinical trials and existing drug repurposing trials. Many other important improvements in the content, interface and performance of the DrugBank website have been made and these should greatly enhance its ease of use, utility and potential applications in many areas of pharmacological research, pharmaceutical science and drug education.
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                Author and article information

                Contributors
                Journal
                Comput Struct Biotechnol J
                Comput Struct Biotechnol J
                Computational and Structural Biotechnology Journal
                Research Network of Computational and Structural Biotechnology
                2001-0370
                26 December 2019
                2020
                26 December 2019
                : 18
                : 241-252
                Affiliations
                [a ]NeuroDiderot, UMR 1141, Inserm, Université de Paris, Sorbonne Paris Cité, Hôpital Robert Debré, 48, boulevard Sérurier, Paris 75019, France
                [b ]Université Paris Diderot, Université de Paris, Sorbonne Paris Cité, 5, rue Thomas Mann, Paris 75013, France
                [c ]Univ. Lille, CNRS, Centrale Lille, Inria, UMR 9189 - CRIStAL - Centre de Recherche en Informatique Signal et Automatique de Lille, F-59000 Lille, France
                [d ]Université Paris 13, Sorbonne Paris Cité, UFR de santé, médecine et biologie humaine, Bobigny 93000, France
                [e ]Service histologie-embryologie-cytogénétique-biologie de la reproduction-CECOS, Hôpital Jean Verdier, AP-HP, Bondy 93140, France
                Author notes
                [* ]Corresponding author at: NeuroDiderot, UMR 1141, Inserm, Université de Paris, Sorbonne Paris Cité, Hôpital Robert Debré, 48, boulevard Sérurier, Paris 75019, France (A. Delahaye-Duriez). clemence.reda@ 123456inserm.fr andree.delahaye@ 123456inserm.fr
                Article
                S2001-0370(19)30398-8
                10.1016/j.csbj.2019.12.006
                7790737
                33489002
                da67f01e-978b-4aff-9040-a76ffd9ebaad
                © 2019 The Authors

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

                History
                : 29 September 2019
                : 10 December 2019
                : 10 December 2019
                Categories
                Short Survey

                drug discovery,drug repurposing,multi-armed bandit,collaborative filtering,bayesian optimization,adaptive clinical trial

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