Searching across hundreds of databases
Evidence of familial inheritance in non-medullary thyroid cancer (NMTC) has accumulated over the last few decades. However, known variants account for a very small percentage of the genetic burden. Here, we focused on the identification of common pathways and networks enriched in NMTC families to better understand its pathogenesis with the final aim of identifying one novel high/moderate-penetrance germline predisposition variant segregating with the disease in each studied family. We performed whole genome sequencing on 23 affected and 3 unaffected family members from five NMTC-prone families and prioritized the identified variants using our Familial Cancer Variant Prioritization Pipeline (FCVPPv2). In total, 31 coding variants and 39 variants located in upstream, downstream, 5' or 3' untranslated regions passed FCVPPv2 filtering. Altogether, 210 genes affected by variants that passed the first three steps of the FCVPPv2 were analyzed using Ingenuity Pathway Analysis software. These genes were enriched in tumorigenic signaling pathways mediated by receptor tyrosine kinases and G-protein coupled receptors, implicating a central role of PI3K/AKT and MAPK/ERK signaling in familial NMTC. Our approach can facilitate the identification and functional validation of causal variants in each family as well as the screening and genetic counseling of other individuals at risk of developing NMTC.
Pubmed ID: 31614935 RIS Download
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A software tool which predicts whether an amino acid substitution or indel has an impact on the biological function of a protein.
View all literature mentionsDatabase as central repository for both single base nucleotide substitutions and short deletion and insertion polymorphisms. Distinguishes report of how to assay SNP from use of that SNP with individuals and populations. This separation simplifies some issues of data representation. However, these initial reports describing how to assay SNP will often be accompanied by SNP experiments measuring allele occurrence in individuals and populations. Community can contribute to this resource.
View all literature mentionsSoftware tools for read pair collation based algorithms on BAM files including * bamcollate2: reads BAM and writes BAM reordered such that alignment or collated by query name * bammarkduplicates: reads BAM and writes BAM with duplicate alignments marked using the BAM flags field * bammaskflags: reads BAM and writes BAM while masking (removing) bits from the flags column * bamrecompress: reads BAM and writes BAM with a defined compression setting. This tool is capable of multi-threading. * bamsort: reads BAM and writes BAM resorted by coordinates or query name * bamtofastq: reads BAM and writes FastQ; output can be collated or uncollated by query name
View all literature mentionsTHIS RESOURCE IS NO LONGER IN SERVICE. Documented on January 9, 2023. An aggregated data platform for genome sequencing data created by a coalition of investigators seeking to aggregate and harmonize exome sequencing data from a variety of large-scale sequencing projects, and to make summary data available for the wider scientific community. The data set provided on this website spans 61,486 unrelated individuals sequenced as part of various disease-specific and population genetic studies. They have removed individuals affected by severe pediatric disease, so this data set should serve as a useful reference set of allele frequencies for severe disease studies. All of the raw data from these projects have been reprocessed through the same pipeline, and jointly variant-called to increase consistency across projects. They ask that you not publish global (genome-wide) analyses of these data until after the ExAC flagship paper has been published, estimated to be in early 2015. If you''re uncertain which category your analyses fall into, please email them. The aggregation and release of summary data from the exomes collected by the Exome Aggregation Consortium has been approved by the Partners IRB (protocol 2013P001477, Genomic approaches to gene discovery in rare neuromuscular diseases).
View all literature mentionsA database for functional prediction and annotation of all potential non-synonymous single-nucleotide variants (nsSNVs) in the human genome. Version 2.0 is based on the Gencode release 9 / Ensembl version 64 and includes a total of 87,347,043 nsSNVs and 2,270,742 essential splice site SNVs. It compiles prediction scores from six prediction algorithms (SIFT, Polyphen2, LRT, MutationTaster, MutationAssessor and FATHMM), three conservation scores (PhyloP, GERP++ and SiPhy) and other related information including allele frequencies observed in the 1000 Genomes Project phase 1 data and the NHLBI Exome Sequencing Project, various gene IDs from different databases, functional descriptions of genes, gene expression and gene interaction information, etc. Some dbNSFP contents (may not be up-to-date though) can also be accessed through variant tools, ANNOVAR, KGGSeq, UCSC Genome Browser''s Variant Annotation Integrator, Ensembl Variant Effect Predictor and HGMD.
View all literature mentionsA web server for functional annotation of novel and publicly known genetic variants that was developed to assess the potential significance of known and novel SNPs on the major transcriptome, proteome, regulatory and structural variation models in order to identify the phenotypically important variants. A broader range of variations have been incorporated such as insertions / deletions, block substitutions, IUPAC codes submission and region-based analysis, expanding the query size limit, and most importantly including additional categories for the assessment of functional impact. SNPnexus provides a comprehensive set of annotations for genomic variation data by characterizing related functional consequences at the transcriptome/proteome levels of seven major annotation systems with in-depth analysis of potential deleterious effects, inferring physical and cytogenetic mapping, reporting information on HapMap genotype/allele data, finding overlaps with potential regulatory elements, structural variations and conserved elements, and retrieving links with previously reported genetic disease studies.
View all literature mentionsDatabase of known and predicted protein interactions. The interactions include direct (physical) and indirect (functional) associations and are derived from four sources: Genomic Context, High-throughput experiments, (Conserved) Coexpression, and previous knowledge. STRING quantitatively integrates interaction data from these sources for a large number of organisms, and transfers information between these organisms where applicable. The database currently covers 5''214''234 proteins from 1133 organisms. (2013)
View all literature mentionsTHIS RESOURCE IS NO LONGER IN SERVICE. Documented on May 16,2023. Software tool designed for efficient and accurate variant detection in high throughput sequencing data. Haplotype based variant caller for next generation sequence data.
View all literature mentionsEvaluates disease-causing potential of sequence alterations.
View all literature mentionsWeb tool to predict biological targets of miRNAs by searching for presence of conserved 8mer, 7mer and 6mer sites that match seed region of each miRNA. Nonconserved sites are also predicted and sites with mismatches in seed region that are compensated by conserved 3' pairing. Used to search for predicted microRNA targets in mammals.
View all literature mentionsData analysis service to predict whether an amino acid substitution affects protein function based on sequence homology and the physical properties of amino acids. SIFT can be applied to naturally occurring nonsynonymous polymorphisms and laboratory-induced missense mutations. (entry from Genetic Analysis Software) Web service is also available.
View all literature mentionsWeb server predicts functional impact of amino-acid substitutions in proteins, such as mutations discovered in cancer or missense polymorphisms. Functional impact is assessed based on evolutionary conservation of affected amino acid in protein homologs.
View all literature mentionsThe SciCrunch Infrastructure was developed as a cooperative data platform to be used by diverse communities in making data more FAIR.
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