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      Therapeutic target database update 2018: enriched resource for facilitating bench-to-clinic research of targeted therapeutics

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          Abstract

          Extensive efforts have been directed at the discovery, investigation and clinical monitoring of targeted therapeutics. These efforts may be facilitated by the convenient access of the genetic, proteomic, interactive and other aspects of the therapeutic targets. Here, we describe an update of the Therapeutic target database (TTD) previously featured in NAR. This update includes: (i) 2000 drug resistance mutations in 83 targets and 104 target/drug regulatory genes, which are resistant to 228 drugs targeting 63 diseases (49 targets of 61 drugs with patient prevalence data); (ii) differential expression profiles of 758 targets in the disease-relevant drug-targeted tissue of 12 615 patients of 70 diseases; (iii) expression profiles of 629 targets in the non-targeted tissues of 2565 healthy individuals; (iv) 1008 target combinations of 1764 drugs and the 1604 target combination of 664 multi-target drugs; (v) additional 48 successful, 398 clinical trial and 21 research targets, 473 approved, 812 clinical trial and 1120 experimental drugs, and (vi) ICD-10-CM and ICD-9-CM codes for additional 482 targets and 262 drugs against 98 disease conditions. This update makes TTD more useful for facilitating the patient focused research, discovery and clinical investigations of the targeted therapeutics. TTD is accessible at http://bidd.nus.edu.sg/group/ttd/ttd.asp.

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          Most cited references62

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          Basic local alignment search tool.

          A new approach to rapid sequence comparison, basic local alignment search tool (BLAST), directly approximates alignments that optimize a measure of local similarity, the maximal segment pair (MSP) score. Recent mathematical results on the stochastic properties of MSP scores allow an analysis of the performance of this method as well as the statistical significance of alignments it generates. The basic algorithm is simple and robust; it can be implemented in a number of ways and applied in a variety of contexts including straightforward DNA and protein sequence database searches, motif searches, gene identification searches, and in the analysis of multiple regions of similarity in long DNA sequences. In addition to its flexibility and tractability to mathematical analysis, BLAST is an order of magnitude faster than existing sequence comparison tools of comparable sensitivity.
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            NCBI GEO: archive for functional genomics data sets—update

            The Gene Expression Omnibus (GEO, http://www.ncbi.nlm.nih.gov/geo/) is an international public repository for high-throughput microarray and next-generation sequence functional genomic data sets submitted by the research community. The resource supports archiving of raw data, processed data and metadata which are indexed, cross-linked and searchable. All data are freely available for download in a variety of formats. GEO also provides several web-based tools and strategies to assist users to query, analyse and visualize data. This article reports current status and recent database developments, including the release of GEO2R, an R-based web application that helps users analyse GEO data.
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              KEGG as a reference resource for gene and protein annotation

              KEGG (http://www.kegg.jp/ or http://www.genome.jp/kegg/) is an integrated database resource for biological interpretation of genome sequences and other high-throughput data. Molecular functions of genes and proteins are associated with ortholog groups and stored in the KEGG Orthology (KO) database. The KEGG pathway maps, BRITE hierarchies and KEGG modules are developed as networks of KO nodes, representing high-level functions of the cell and the organism. Currently, more than 4000 complete genomes are annotated with KOs in the KEGG GENES database, which can be used as a reference data set for KO assignment and subsequent reconstruction of KEGG pathways and other molecular networks. As an annotation resource, the following improvements have been made. First, each KO record is re-examined and associated with protein sequence data used in experiments of functional characterization. Second, the GENES database now includes viruses, plasmids, and the addendum category for functionally characterized proteins that are not represented in complete genomes. Third, new automatic annotation servers, BlastKOALA and GhostKOALA, are made available utilizing the non-redundant pangenome data set generated from the GENES database. As a resource for translational bioinformatics, various data sets are created for antimicrobial resistance and drug interaction networks.
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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
                04 January 2018
                13 November 2017
                13 November 2017
                : 46
                : Database issue , Database issue
                : D1121-D1127
                Affiliations
                Bioinformatics and Drug Design Group, Department of Pharmacy and Center for Computational Science and Engineering, National University of Singapore, Singapore 117543, Singapore
                Innovative Drug Research and Bioinformatics Group, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
                Innovative Drug Research and Bioinformatics Group, School of Pharmaceutical Sciences, Chongqing University, Chongqing 401331, China
                Zhejiang Key Laboratory of Gastro-intestinal Pathophysiology, Zhejiang Hospital of Traditional Chinese Medicine, Zhejiang Chinese Medical University, Hangzhou 310006, China
                Author notes
                To whom correspondence should be addressed. Tel: +86 571 88208416; Fax: +86 571 88208416; Email: zhufeng.ns@ 123456gmail.com ; zhufeng@ 123456zju.edu.cn . Correspondence may also be addressed to Yu Zong Chen. Tel: +65 65166877; Fax: +65 67746756; Email: phacyz@ 123456nus.edu.sg

                These authors contributed equally to the paper as first authors.

                Author information
                http://orcid.org/0000-0003-3629-519X
                http://orcid.org/0000-0003-3629-519X
                http://orcid.org/0000-0003-3629-519X
                http://orcid.org/0000-0001-8069-0053
                Article
                gkx1076
                10.1093/nar/gkx1076
                5753365
                29140520
                db857a93-d3a3-4680-938f-495c853c3799
                © The Author(s) 2017. 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 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
                : 10 November 2017
                : 12 October 2017
                : 15 September 2017
                Page count
                Pages: 7
                Categories
                Database Issue

                Genetics
                Genetics

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