A Survey of Computational Tools to Analyze and Interpret Whole Exome Sequencing Data <s> Computational Tools for Linking Variants to Treatments. <s> The Pharmacogenomics Knowledgebase (PharmGKB) is a resource that collects, curates, and disseminates information about the impact of human genetic variation on drug responses. It provides clinically relevant information, including dosing guidelines, annotated drug labels, and potentially actionable gene-drug associations and genotype-phenotype relationships. Curators assign levels of evidence to variant-drug associations using well-defined criteria based on careful literature review. Thus, PharmGKB is a useful source of high-quality information supporting personalized medicine-implementation projects. <s> BIB001 </s> A Survey of Computational Tools to Analyze and Interpret Whole Exome Sequencing Data <s> Computational Tools for Linking Variants to Treatments. <s> The cBio Cancer Genomics Portal (http://cbioportal.org) is an open-access resource for interactive exploration of multidimensional cancer genomics data sets, currently providing access to data from more than 5,000 tumor samples from 20 cancer studies. The cBio Cancer Genomics Portal significantly lowers the barriers between complex genomic data and cancer researchers who want rapid, intuitive, and high-quality access to molecular profiles and clinical attributes from large-scale cancer genomics projects and empowers researchers to translate these rich data sets into biologic insights and clinical applications. <s> BIB002 </s> A Survey of Computational Tools to Analyze and Interpret Whole Exome Sequencing Data <s> Computational Tools for Linking Variants to Treatments. <s> ClinVar (http://www.ncbi.nlm.nih.gov/clinvar/) provides a freely available archive of reports of relationships among medically important variants and phenotypes. ClinVar accessions submissions reporting human variation, interpretations of the relationship of that variation to human health and the evidence supporting each interpretation. The database is tightly coupled with dbSNP and dbVar, which maintain information about the location of variation on human assemblies. ClinVar is also based on the phenotypic descriptions maintained in MedGen (http://www.ncbi.nlm.nih.gov/medgen). Each ClinVar record represents the submitter, the variation and the phenotype, i.e. the unit that is assigned an accession of the format SCV000000000.0. The submitter can update the submission at any time, in which case a new version is assigned. To facilitate evaluation of the medical importance of each variant, ClinVar aggregates submissions with the same variation/phenotype combination, adds value from other NCBI databases, assigns a distinct accession of the format RCV000000000.0 and reports if there are conflicting clinical interpretations. Data in ClinVar are available in multiple formats, including html, download as XML, VCF or tab-delimited subsets. Data from ClinVar are provided as annotation tracks on genomic RefSeqs and are used in tools such as Variation Reporter (http://www.ncbi.nlm.nih.gov/variation/tools/reporter), which reports what is known about variation based on user-supplied locations. <s> BIB003 </s> A Survey of Computational Tools to Analyze and Interpret Whole Exome Sequencing Data <s> Computational Tools for Linking Variants to Treatments. <s> DrugBank (http://www.drugbank.ca) is a comprehensive online database containing extensive biochemical and pharmacological information about drugs, their mechanisms and their targets. Since it was first described in 2006, DrugBank has rapidly evolved, both in response to user requests and in response to changing trends in drug research and development. Previous versions of DrugBank have been widely used to facilitate drug and in silico drug target discovery. The latest update, DrugBank 4.0, has been further expanded to contain data on drug metabolism, absorption, distribution, metabolism, excretion and toxicity (ADMET) and other kinds of quantitative structure activity relationships (QSAR) information. These enhancements are intended to facilitate research in xenobiotic metabolism (both prediction and characterization), pharmacokinetics, pharmacodynamics and drug design/discovery. For this release, >1200 drug metabolites (including their structures, names, activity, abundance and other detailed data) have been added along with >1300 drug metabolism reactions (including metabolizing enzymes and reaction types) and dozens of drug metabolism pathways. Another 30 predicted or measured ADMET parameters have been added to each DrugCard, bringing the average number of quantitative ADMET values for Food and Drug Administration-approved drugs close to 40. Referential nuclear magnetic resonance and MS spectra have been added for almost 400 drugs as well as spectral and mass matching tools to facilitate compound identification. This expanded collection of drug information is complemented by a number of new or improved search tools, including one that provides a simple analyses of drug–target, –enzyme and –transporter associations to provide insight on drug–drug interactions. <s> BIB004 </s> A Survey of Computational Tools to Analyze and Interpret Whole Exome Sequencing Data <s> Computational Tools for Linking Variants to Treatments. <s> Summary: We report the creation of Drug Signatures Database (DSigDB), a new gene set resource that relates drugs/compounds and their target genes, for gene set enrichment analysis (GSEA). DSigDB currently holds 22 527 gene sets, consists of 17 389 unique compounds covering 19 531 genes. We also developed an online DSigDB resource that allows users to search, view and download drugs/compounds and gene sets. DSigDB gene sets provide seamless integration to GSEA software for linking gene expressions with drugs/compounds for drug repurposing and translational research. ::: ::: Availability and implementation: DSigDB is freely available for non-commercial use at http://tanlab.ucdenver.edu/DSigDB. ::: ::: Supplementary information: Supplementary data are available at Bioinformatics online. ::: ::: Contact: ude.revnedcu@nat.noohckia <s> BIB005
The ability to link variants with actionable drug targets is an emerging research topic in precision medicine. Databases such as My Cancer Genome have provided the framework for these studies (https://www.mycancergenome.org/). My Cancer Genome provides a bridge between genomic data and clinical therapeutic treatments. Similarly, ClinVar provides information on the relationship between variants and clinical therapy BIB003 . By collecting both the variants and the clinical significance related to these variants, ClinVar offers a database for researchers to explore the significance of sequencing findings in the clinical setting BIB003 . Pharmacological databases such as PharmGKB BIB001 , DrugBank BIB004 , and DSigDB BIB005 provide the link between drug and drug targets (variants). For example, by querying a list of variants to one of these databases, it allows users to identify actionable targets via enrichment analysis for the repurposing of drugs. Similarly, the ability to incorporate clinical data into sequencing studies is vital to the advancement of personalized medicine. However, due to the lack of integration between electronic health records (EHR) and molecular analysis, this remains one of the challenges in translating WES data analysis into clinical practice. Projects such as cBioPortal provide a framework for incorporating sequencing data with available clinical data BIB002 . New methods for addressing this task are urgently needed to take advantage of the important applications of WES data within the clinic in order to advance precision medicine.