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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

01/03/2013 UK NEQAS UV Participants Meeting 2013

AlamutDatabas

e

RefSeq dbSNP

-Genome-Transcripts

HUGO

InterPro

DomainsVariants

Genes

-Proteins-Missense variants

+OrthologuesLSDBs

Abstracts

Conservation

Mutations

4

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