232
views
0
recommends
+1 Recommend
1 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Computational drug repositioning based on side-effects mined from social media

      research-article

      Read this article at

      ScienceOpenPublisher
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Drug repositioning methods attempt to identify novel therapeutic indications for marketed drugs. Strategies include the use of side-effects to assign new disease indications, based on the premise that both therapeutic effects and side-effects are measurable physiological changes resulting from drug intervention. Drugs with similar side-effects might share a common mechanism of action linking side-effects with disease treatment, or may serve as a treatment by “rescuing” a disease phenotype on the basis of their side-effects; therefore it may be possible to infer new indications based on the similarity of side-effect profiles. While existing methods leverage side-effect data from clinical studies and drug labels, evidence suggests this information is often incomplete due to under-reporting. Here, we describe a novel computational method that uses side-effect data mined from social media to generate a sparse undirected graphical model using inverse covariance estimation with ℓ 1-norm regularization. Results show that known indications are well recovered while current trial indications can also be identified, suggesting that sparse graphical models generated using side-effect data mined from social media may be useful for computational drug repositioning.

          Most cited references70

          • Record: found
          • Abstract: found
          • Article: not found

          Sparse inverse covariance estimation with the graphical lasso.

          We consider the problem of estimating sparse graphs by a lasso penalty applied to the inverse covariance matrix. Using a coordinate descent procedure for the lasso, we develop a simple algorithm--the graphical lasso--that is remarkably fast: It solves a 1000-node problem ( approximately 500,000 parameters) in at most a minute and is 30-4000 times faster than competing methods. It also provides a conceptual link between the exact problem and the approximation suggested by Meinshausen and Bühlmann (2006). We illustrate the method on some cell-signaling data from proteomics.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: found
            Is Open Access

            Cytoscape Web: an interactive web-based network browser

            Summary: Cytoscape Web is a web-based network visualization tool–modeled after Cytoscape–which is open source, interactive, customizable and easily integrated into web sites. Multiple file exchange formats can be used to load data into Cytoscape Web, including GraphML, XGMML and SIF. Availability and Implementation: Cytoscape Web is implemented in Flex/ActionScript with a JavaScript API and is freely available at http://cytoscapeweb.cytoscape.org/ Contact: gary.bader@utoronto.ca Supplementary information: Supplementary data are available at Bioinformatics online.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              PSICOV: precise structural contact prediction using sparse inverse covariance estimation on large multiple sequence alignments.

              The accurate prediction of residue-residue contacts, critical for maintaining the native fold of a protein, remains an open problem in the field of structural bioinformatics. Interest in this long-standing problem has increased recently with algorithmic improvements and the rapid growth in the sizes of sequence families. Progress could have major impacts in both structure and function prediction to name but two benefits. Sequence-based contact predictions are usually made by identifying correlated mutations within multiple sequence alignments (MSAs), most commonly through the information-theoretic approach of calculating mutual information between pairs of sites in proteins. These predictions are often inaccurate because the true covariation signal in the MSA is often masked by biases from many ancillary indirect-coupling or phylogenetic effects. Here we present a novel method, PSICOV, which introduces the use of sparse inverse covariance estimation to the problem of protein contact prediction. Our method builds on work which had previously demonstrated corrections for phylogenetic and entropic correlation noise and allows accurate discrimination of direct from indirectly coupled mutation correlations in the MSA. PSICOV displays a mean precision substantially better than the best performing normalized mutual information approach and Bayesian networks. For 118 out of 150 targets, the L/5 (i.e. top-L/5 predictions for a protein of length L) precision for long-range contacts (sequence separation >23) was ≥ 0.5, which represents an improvement sufficient to be of significant benefit in protein structure prediction or model quality assessment. The PSICOV source code can be downloaded from http://bioinf.cs.ucl.ac.uk/downloads/PSICOV.
                Bookmark

                Author and article information

                Contributors
                Journal
                peerj-cs
                PeerJ Computer Science
                PeerJ Comput. Sci.
                PeerJ Inc. (San Francisco, USA )
                2376-5992
                24 February 2016
                : 2
                : e46
                Affiliations
                [-1] Thomson Reuters, Corporate Research and Development , London, United Kingdom
                Article
                cs-46
                10.7717/peerj-cs.46
                cb969a09-e7b7-419f-8aa8-cb40feb7c712
                © 2016 Nugent et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ Computer Science) and either DOI or URL of the article must be cited.

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ Computer Science) and either DOI or URL of the article must be cited.

                History
                : 29 September 2015
                : 26 January 2016
                Funding
                Funded by: Thomson Reuters Global Resources
                This research was funded by Thomson Reuters Global Resources. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Bioinformatics
                Data Mining and Machine Learning
                Computational Biology
                Social Computing

                Computer science
                Drug repositioning,Drug repurposing,Side-effect,Adverse drug reaction,Social media,Graphical model,Graphical lasso,Inverse covariance estimation

                Comments

                Comment on this article