The quality conundrum: A global perspective on healthcare ...
in a quality perspective
description
Transcript of in a quality perspective
01/03/2013 UK NEQAS UV Participants Meeting 2013
in a quality perspective
AlamutAlamut
• Gene browser over 18,000+ human protein-coding genes
• Advanced visualization of gene-related annotations
• Integration of prediction tools• Variant management and reporting• HGVS nomenclature compliancy
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AlamutAlamut
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Ref. GenomeRef. Genome
ConservationConservation
Ref. transcripts
Ref. transcripts
dbSNP variations
dbSNP variations
ESP variationsESP variations
HGMD mutations
HGMD mutations
Protein domainsProtein
domains
OrthologuesOrthologues
Data SourcesData Sources
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AlamutDatabas
e
RefSeq dbSNP
-Genome-Transcripts
HUGO
InterPro
DomainsVariants
Genes
-Proteins-Missense variants
+OrthologuesLSDBs
Abstracts
Conservation
Mutations
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NHLBI GO ESP
Missense PredictionsMissense Predictions
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Splicing PredictionsSplicing Predictions
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Exercise Critical Judgment!Exercise Critical Judgment!
• Software =
Program code+Data
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Exercise Critical Judgment!Exercise Critical Judgment!
• Software =
Program code + bugs+Data + errors
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Exercise Critical Judgment!Exercise Critical Judgment!
• Software =
Program code + bugs+Data + errors
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DataData
• dbSNP is not a database of polymorphisms
• Conservation scores depend on sequences and alignment algorithms
• Transcripts can be misplaced (very unusual)• Protein domains are mostly predicted• Orthologues are mostly computed
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Missense PredictionsMissense Predictions
• Why Align GVGD, PolyPhen-2, SIFT, MutationTaster?– Reputation– Automatability– Right to use in commercial software
• Complex algorithms based on AA physico-chemical properties, AA conservation, protein structure, and more
• Predictions ±strongly depend on Alamut-supplied orthologue alignment
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Splicing PredictionsSplicing Predictions
• Why SSF, MaxEnt, NNSPLICE, GeneSplicer, HSF?– ditto
• Simple algorithms based on sequence• MaxEnt often considered as the most accurate• (Splicing regulation predictions: for experts
only!)
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Quality ContributionQuality Contribution
• Up-to-date data• Visual feedback• HGVS nomenclature (when in doubt check
with Mutalyzer)• Manually-curated orthologue alignments• NGS alignment and coverage visualization
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NGS Alignment ViewerNGS Alignment Viewer
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Alamut / CMGS-VKGL GuidelinesAlamut / CMGS-VKGL Guidelines• 3.3 Variant Nomenclature• 3.4 Variant Submission• 4.1 LSDBs• 4.2 SNP Databases• 4.7 Species Conservation• 4.8 Missense Predictions• 4.9 Splice Site Predictions• 4.14 Interpretation Process Standardization• 5.1 Reporting Variants• 5.4 Variant Classification
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34 labs