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Church_NCBIvariation2013
- 1. Variation Resources at NCBI Deanna M. Church Staff Scientist, NCBI @deannachurch
- 2. Variation Resources Team at NCBI Ming Ward Lon Phan Brad Holmes Anna Glodek Michael Kholodov Rama Maiti Juliana Sampson David Shao Eugene Shekhtman Qiang Wang Hua Zhang Key Collaborators Heidi Rehm, Harvard Partners Christa Lese Martin, Geisinger Sherri Bale, GeneDx Lisa Kalman, CDC Birgit Funke, Harvard Partners Madhuri Hegde, Emory Donna Maglott Melissa Landrum Jennifer Lee George Riley Ray Tully Craig Wallin Shanmuga Chitipiralla Douglas Hoffman Wonhee Jang Ken Katz Michael Ovetsky Ricardo Villamarin Tim Hefferon John Lopez John Garner Chao Chen
- 4. Data from external sources dbSNP dbVar ClinVar GTR Quality Control Ref variants References Annotations Visualization Tools
- 5. Variant Definitions Location Evidence Methodology dbSNP dbVar Variant Annotations Phenotypes Consequences Tests Other Biology ClinVar GTR dbSNP
- 7. GenBank vs RefSeq Submitter Owned RefSeq Owned Redundancy Updated rarely INSDC Non-Redundant Curated Not INSDC BRCA1 83 genomic records 31 mRNA records 27 protein records 3 genomic records 5 mRNA records 1 RNA record 5 protein records
- 8. Genome Res. 1999. 9: 677-679 http://www.ncbi.nlm.nih.gov/snp
- 10. SNPs defined by flanking position >gnl|dbSNP|ss76078129|allelePos=17|len=33|alleles='A/G’ GTGGCAGAGA CTGAAT R AAGGGTTGAC CCAGGG >gnl|dbSNP|ss3354770|allelePos=499|len=661|alleles='T/C’ actattcaca atagcaaaga cttggaacca acccaaatgt ccaacaatga tagactggat taagaaaatg tggcacatat acaccatgga atactaggca TTCCATTCTA CTGTGCACGA GTCACTGCAA ACTCAAGCAT TTCCAGAGTT CTGAAAGCTC AACTAAGAAC CAAGCCTACT CATTCAACAT CAACACACAC AGCACCCTGA GCGTCCAAAA CCACGGGGGT TATGTTCTAG ACCACAGGAC TGGCTACCTG GCCCTGCTCA AGGCGGCAGG ATCAATGGGC AAGAATGTGC AAGAATTTAC CACAACTCAG CCTTGCTGTG TCAACCACAG AGGCCAAGTA CCCCTAACAC CCAGATAGAG TAATTGTGCC TTACTTCTTT GTTCATTCCC ACCATTACAT TTTGTAAATT GGAACTTCTA GGAGGTTAGA AGGATATGCT GATCAAAAAA AGGGGACATA TTCAAGGAGT GTCCCTGGGT CAACCCTT Y ATTCAGTCTC TGCCACATGT CTAGTAACTG TGAGTGATGG GTGCATCAGT ATAATCCTGA GCCTCCCAAG GTACAGCCTT TCACTACTAT TCATCATATT GGCTAAGGTA TTCATCATAT TGGCTAAGGT ATTCACCAAC AGGGCTCATT TTCTATCAGA CC
- 11. ss76078129 'A/G’ ss3354770 'T/C’ ss3354770 (aligns to minus strand) ss76078129 (aligns to plus strand) ss76078129 (33bp) ss76078129 (661bp)
- 13. rs397515413
- 15. VCF (Variant Call File) Defines variant by location rather than flanking sequence
- 18. rs62645748 To be replaced by a Variation Viewer To be replaced by a link to ClinVar
- 19. rs62645748 (NCBI Homo sapiens annotation run 104)
- 21. Submitter Information Contact and author information Study Information Study meta-data (description, PMID, ProjectID, etc) Sample/Sampleset data Experiment data Variants Sample IDs (if samples are consented) Sampleset ID for pooled samples (case v control sets) Assay method (sequencing, array) Platform and analysis information Variant definitions
- 23. Variant Call Ambiguity start stop Probes with decreased signal intensity Probes with expected signal intensity breakpoint breakpoint Inner start Inner stop Outer start Outer stop Inner start Inner stop
- 24. Fosmid clone (40 Kb +/- 1 Kb) Variant Call Ambiguity Outer start Outer stop 20Kb Clone has a deletion relative to the genome 60 Kb Clone has an insertion relative to the genome
- 28. ClinVar data model and display Allele Variant Variant Phenotype Variant Phenotype Submitter RCV RCV SCV SCV SCV SCV SCV SCV
- 29. ClinVar RCV report - Overview Interpretation • Significance • Review status * • Accession.version * Allele summary • Gene • Variant type • Genomic location • HGVS expressions* • Molecular consequence* • Links* • Frequency* Phenotype summary • Names • Links* • Age of onset * • Prevalence * * May be provided by NCBI
- 30. ClinVar RCV report – Summary of assertions • Each submission is accessioned and versioned • Terms provided by the submitter are mapped to controlled values • Method of review is clearly reported so primary data can be distinguished from that reported in the literature
- 31. ClinVar RCV report - Evidence
- 32. Allele report – available December
- 36. From Assembly 1 <-> Assembly 2 Assembly <-> RefSeqGene/LRG Primary Assembly <-> Alternate loci http://www.ncbi.nlm.nih.gov/genome/tools/remap
- 37. 1:215844373
- 38. This new look coming next month http://www.ncbi.nlm.nih.gov/variations/tools/reporter
- 42. Target audience: Clinical testing labs Submissions from: Clinical and Research labs NA Concordant Discordant Calls Tests cSRA http://www.ncbi.nlm.nih.gov/variation/tools/get-rm
- 43. Twelve submitting labs to date Twelve custom scripts to regularize data Defined formats here: http://www.ncbi.nlm.nih.gov/projects/variation/get-rm
- 44. Platforms NA12878 Tests by Platform 30 25 20 15 10 5 0 HiSeq 2000 HiSeq 2500 MiSeq Ion Torrent Sanger 454
- 45. Lab Provided Validation Variants validated in this sample using another platform Variants validated in another sample using another platform Variants seen in other samples from submitting lab using this platform Variants seen in public data set Variants that are novel Variants that were not assessed
- 46. Suppor ng Read Counts 250 Number of Variant 200 150 100 50 0 0 10 Based on May 2013 Data release 50 100 500 Read Count Bins 1000 5000
- 47. Based on May 2013 Data release
- 50. Gene level concordance Σ (max(xi)/Σ T) i = genotype call X = count per call for each variant T = total genotype calls per variant Sums are taken over all variants in a gene. Tested regions taken into account Phasing ignored
Notas do Editor
- Put plug for Tim here…
- RefSeqGene/LRG screen shot: stable coordinate system for gene level reporting. Gene centric genomic sequences.
- Distribution of RefSeqGenes on GRCh37
- Remap