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NCBI Clinical Variation Resources
Andrew Stubbs
Clinical Bioinformatics Unit
Department of Pathology
Arne Ijpma
Genetic Variation
SNP SNP Indel Indel
Entrez Gene Loci http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene
NR-Pro
RefSeq
ESTs
Entrez Gene
Genscan
GrailEXP
FGENESH
Transcript & protein Variation
Functional consequences
Functional consequences Effect of annotation on functional Impact
Functional consequences REFSEQ-normalised heatmap of annotation comparison
Clinical Interpretation
Clinical Interpretation
Volume 15 | Number 9 | September 2013
Volume 15 | Number 7 | July 2013
NCBI Genomics
NCBI Database Resources
-Database of Short Genetic Variations
(dbSNP)
-Database of Genomic Structural Variation
(dbVar)
-BioProject (formerly Genome Project)
DATABASES
-Database of Genotypes and Phenotypes
(dbGaP)
-Online Mendelian Inheritance in Man
(OMIM)
-Genetic Testing Registry (GTR)
DATABASES
http://www.ncbi.nlm.nih.gov/guide/variation/
NCBI Database Resources Non-Clinical
Database of Short Genetic Variations (dbSNP): Includes single nucleotide variations, microsatellites, and small-scale insertions and deletions
Database of Genomic Structural Variation (dbVar): Large scale genomic variation, including large insertions, deletions, translocations and inversions and associated phenotype information.
Database of Major Histocompatibility Complex (dbMHC) : Interactive Alignment Viewer for HLA and related genes, an MHC microsatellite database, a sequence interpretation site for Sequencing Based Typing (SBT), and a Primer/Probe database.
Database of Genotypes and Phenotypes (dbGaP): genotype and phenotype. These studies include genome-wide association (GWAS), medical resequencing, molecular diagnostic assays, as well as association between genotype and non-clinical traits.
http://www.ncbi.nlm.nih.gov/guide/variation/
NCBI Database Resources Clinical
ClinVar: A public, tracked record of reported relationships between human variation and observed health status with supporting evidence.
Genetic Testing Registry (GTR) : A voluntary registry of genetic tests and analytic and clinical validity.
http://www.ncbi.nlm.nih.gov/guide/variation/
dbSNP database of short genetic variation
dbSNP database of short genetic variation
rs28933093
dbSNP database of short genetic variation
rs28933093
dbSNP database of short genetic variation
rs28933093
HGVS from RefSeq Gene naming conventions
Within a coding region CFTR
Intronic SLC46A1
Flanking and intronic SEPT9
dbVar database of structural variation
http://www.ncbi.nlm.nih.gov/dbvar
dbGaP database of genotypes and phenotypes
dbGaP database of genotypes and phenotypes
dbGaP database of genotypes and phenotypes
OMIM Online Mendelian Inheritance in Man
#310200 - MUSCULAR DYSTROPHY, DUCHENNE TYPE; DMD
OMIM
ClinVar?
ClinVar is a freely accessible, public archive of reports of the relationships among human variations and phenotypes, with supporting evidence.
http://www.ncbi.nlm.nih.gov/clinvar/intro/
ClinVar integrates results from four domains
ClinVar Review Status
Viewing ClinVar Data
Viewing ClinVar Data
Viewing ClinVar Data
ClinVar Submission Totals
ClinGen & ClinVar
ClinGen Overview
ClinGen Goals
ClinGen Dataflow
GTR Genetic testing registry
GTR Genetic testing registry
GTR Genetic testing registry
MedGen NCBI Portal to Medical Genetics
MedGen is NCBI's portal to information related to Medical Genetics. Terms from the NIH Genetic Testing Registry (GTR), UMLS, HPO, Orphanet, ClinVar and other sources are aggregated into concepts, each of which is assigned a unique identifier and a preferred name and symbol.
The core content of the record may include names, identifiers used by other databases, mode of inheritance, clinical features, and map location of the underlying genetic basis.
MedGen provides links to such resources as 1. Genetic tests registered in the NIH Genetic Testing Registry (GTR) 2. GeneReviews 3. OMIM 4. Related genes 5. Disorders with similar clinical features 6. Medical and research literature 7. Practice guidelines 8. Consumer resources 9. Ontologies such as HPO and ORDO
Quick start guide http://www.ncbi.nlm.nih.gov/medgen/docs/help/#start
MedGen access from ClinVar
MedGen
MedGen
GenomeConnect Benefits of Sharing Patient Data
Genomics In Medicine
Diseases
Genomic Variation
Phenotypes/ Diseases
Publications
Studies
Assays
NCBI Portal
Genomics In Medicine
Diseases
Genomic Variation
Phenotypes/ Diseases
Publications
Studies
Assays
PUBMED
dbSNP
GTR
dbGaP
OMIM
dbVAR
BioProject
NCBI Portal MedGen
NCBI Genomics
NCBI Clinical Variation Resources PRACTICALS
Andrew Stubbs
Graphical Sequence Viewer Graphical Sequence Viewer (http://www.ncbi.nlm.nih.gov/projects/sviewer/) is the graphical display for the Nucleotide and Protein databases. The Sequence Viewer on the web and NCBI's Genome Workbench are based on the same code libraries and developed by the same team.
Help tutorials 1. Sequence Viewer Navigate objects https://www.youtube.com/watch?v=t_gIOYlSlvQ&feature=youtu.be 2. Use BLAST https://www.youtube.com/watch?v=cSlW05LDMlM&list=PL76D7EE6A6A8AC1C3
Graphical Sequence Viewer Example Links: • Human chromosome: NC_000001 This link provides a look at human chromosome 1. There are two panels
shown by default: an overview panel showing the density of annotated genes along with a select number of genes for reference; and a zoomed in graphical view showing a region of the chromosome itself.
• Human reference genomic region: NG_000007 This link shows a reference genomic region − that is, a genomic region that has undergone substantial curation by staff at NCBI. This particular record shows the beta globin locus on chromosome 11. Two panels are shown by default: an overview panel showing the density of annotated genes along with a select number of genes for reference; and a zoomed in graphical view showing individual features on the record.
• MGC mRNA: BC066124.1 This link shows a sample mRNA sequence from the Mammalian Genome Collection. This link will open with two views by default: a graphical panel showing the feature annotation on the sequence; and a sequence panel providing the bases of the sequence itself.
• Viral genome: AC_000020, sequence viewport and marker This link provides an example of how a viral genome can be shown. The link will open with three panels (an overview graphical panel; a zoomed in graphical panel; and a sequence panel); additionally, a marker is set at position 800. You can also embed Sequence Viewer on your own page.
Variation Analysis Tools Which tool do I use for .... ? • I have 3000 variant calls. How do I find out which is possibly significant? - Use
Variation Reporter.
• I am studying my favorite gene. How do I find all variants on that gene? - Use Variation Viewer.
• I want to know if my variant has been observed in the 1000 Genomes study. - Use the 1000 Genomes Browser.
• I have a VCF file in GRCh37 coordinates. How do I move those to GRCh38 coordinates? - Use the NCBI Genome Remapping Service.
• I want to search the NHGRI GWAS Catalog for studies related to Basal Cell Carcinoma. - Use PheGenI.
Variation Analysis Tools Variation Viewer Variation Viewer is a tool for interactive examination and download of nucleotide variants for a specific locus. It supports both the GRCh38 and GRCh37.p13 assemblies. Variation Viewer integrates data from all of the NCBI Variation databases and presents them in a coupled graphical and tabular report. The resulting list of variants can be saved locally using the download function. You can also upload their own variant data to this browser. More information can be found on the NCBI Variation Viewer Fact sheet and in an introductory video tutorial. 1000k Genomes Viewer https://www.youtube.com/watch?v=76gLdUT712c&index=4&list=PL76D7EE6A6A8AC1C3&nohtml5=False
Desktop analysis
http://www.ncbi.nlm.nih.gov/tools/gbench/
Desktop analysis Please follow the tutorials located at: Genome Workbench http://www.ncbi.nlm.nih.gov/tools/gbench/tutorial1/ Genes and Variant http://www.ncbi.nlm.nih.gov/tools/gbench/tutorial4/ Working with BAM files Use the files located on the training drive • A sorted BAM file with index and coverage graph • A sorted BAM file with index and no coverage graph http://www.ncbi.nlm.nih.gov/tools/gbench/tutorial4/ Example Loading a Genome https://www.youtube.com/watch?v=6K6pimaFpiQ
NCBI Genomics
Acknowledgements
• NCBI staff for providing slides and online teaching resources.
• This presentation generated from the online information provided by many NCBI authors including but not exclusively, Ben Busby. Slides from Justine Peeters and Mario Pescatori (Health e-genomics).
• Frank and Sharesma from Erasmus MC for organising this course
