Transcript Alamut HT
in a quality perspective 01/03/2013 UK NEQAS UV Participants Meeting 2013 Alamut • Gene browser over 18,000+ human proteincoding genes • Advanced visualization of gene-related annotations • Integration of prediction tools • Variant management and reporting • HGVS nomenclature compliancy 01/03/2013 UK NEQAS UV Participants Meeting 2013 2 Alamut Ref. Genome Conservation Ref. transcripts dbSNP variations ESP variations HGMD mutations Protein domains Orthologues 01/03/2013 UK NEQAS UV Participants Meeting 2013 3 Data Sources dbSNP NHLBI GO ESP RefSeq InterPro -Genome -Transcripts Variants LSDBs Domains +Orthologues Conservation Genes HUGO -Proteins -Missense variants Abstracts 01/03/2013 Alamut Database UK NEQAS UV Participants Meeting 2013 Mutations 4 Missense Predictions 01/03/2013 UK NEQAS UV Participants Meeting 2013 5 Splicing Predictions 01/03/2013 UK NEQAS UV Participants Meeting 2013 6 Exercise Critical Judgment! • Software = Program code + Data 01/03/2013 UK NEQAS UV Participants Meeting 2013 7 Exercise Critical Judgment! • Software = Program code + bugs + Data + errors 01/03/2013 UK NEQAS UV Participants Meeting 2013 8 Exercise Critical Judgment! • Software = Program code + bugs + Data + errors 01/03/2013 UK NEQAS UV Participants Meeting 2013 9 Data • 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 01/03/2013 UK NEQAS UV Participants Meeting 2013 10 Missense 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 01/03/2013 UK NEQAS UV Participants Meeting 2013 11 Splicing 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!) 01/03/2013 UK NEQAS UV Participants Meeting 2013 12 Quality Contribution • Up-to-date data • Visual feedback • HGVS nomenclature (when in doubt check with Mutalyzer) • Manually-curated orthologue alignments • NGS alignment and coverage visualization 01/03/2013 UK NEQAS UV Participants Meeting 2013 13 NGS Alignment Viewer 01/03/2013 UK NEQAS UV Participants Meeting 2013 14 Alamut / 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 01/03/2013 UK NEQAS UV Participants Meeting 2013 15 34 labs 01/03/2013 UK NEQAS UV Participants Meeting 2013 16