1. Data mining

2. Sequence information Mapping information Phenotypic information Literature Prediction programs -Gene prediction -Promotor prediction -Functional prediction -Structural prediction -Variant annotation

3. http://www.ncbi.nlm.nih.gov/

11. Genome browsers ENSEMBL: http://www.ensembl.org/index.html UCSC : http://genome.ucsc.edu/

12. http://www.ensembl.org/index.html

17. Ensembl Tools

18. http://genome.ucsc.edu/

21. Assembly converter

22. http://dgv.tcag.ca/dgv/app/home

24. https://decipher.sanger.ac.uk/

25. Genomic variant analysis Genomic variants -Mutation: literature, HGMD, gene specific databases -Polymorphism: dbSNP, EVS, ExAC -Prediction programs

26. http://www.ncbi.nlm.nih.gov/SNP/

29. http://evs.gs.washington.edu/EVS/

31. ExAC (http://exac.broadinstitute.org/)

32. ExAC

33. Kaviar: http://db.systemsbiology.net/kaviar/

35. http://sift.jcvi.org/

36. CFTR: p.N1303K

38. Polyphen http://genetics.bwh.harvard.edu/pph2/

40. Mutation Taster http://www.mutationtaster.org/

41. But beware……!!!!! There are many examples of known pathogenic variants predicted to be benign and vice versa

42. Human Splicing Finder http://www.umd.be/HSF/

43. Splice Site Prediction http://www.fruitfly.org/seq_tools/splice.html

44. Splice finder programs GeneSplicer http://www.cbcb.umd.edu/software/ GeneSplicer/gene_spl.shtml Netgene http://www.cbs.dtu.dk/services/Net Gene2/

45. http://scholar.google.be

46. Batch Annotators & Prioritization Gene Panel / Whole Exome Sequencing Large amounts of variants (50-50,000) Needed information for interpretation: Location w.r.t. gene (intron/exon/splicing) Effect on CDS (synonymous/stop-gain/frameshift/...) Severity of the effect Function of gene w.r.t. phenotype Example Applications: wANNOVAR: http://wannovar.usc.eduhttp://wannovar.usc.edu SeattleSeq: http://snp.gs.washington.edu/SeattleSeqAnnotation141/http://snp.gs.washington.edu/SeattleSeqAnnotation141/ VEP: http://www.ensembl.org/Tools/VEPhttp://www.ensembl.org/Tools/VEP VariantDB: http://biomina.be/apps/variantdbhttp://biomina.be/apps/variantdb eXtasy: http://extasy.esat.kuleuven.be/http://extasy.esat.kuleuven.be/ Exomiser: http://www.sanger.ac.uk/science/tools/exomiserhttp://www.sanger.ac.uk/science/tools/exomiser

47. VEP

48. Batch Annotators: wAnnovar

49. NCBIhttp://www.ncbi.nlm.nih.gov/ Ensemblhttp://www.ensemble.org/index.html UCSChttp://genome.ucsc.edu/ Genatlashttp://genatlas.medecine.univ-paris5.fr/ PolyPhenhttp://genetics.bwh.harvard.edu/pph2/ SIFThttp://sift.jcvi.org/ Mutation tasterhttp://www.mutationtaster.org/ Splice predictionhttp://www.umd.be/HSF/ http://www.fruitfly.org/seq_tools/splice.html http://www.cbs.dtu.dk/services/NetGene2/ DECIPHERhttps://decipher.sanger.ac.uk/