SCRIPPS GENOME ADVISER Galina Erikson Senior Bioinformatics Programmer The Scripps Translational Science Institute Scripps Translational Science Institute

As simple as uploading a file: genomics.scripps.edu/ADVISER/ Databases and Algorithms Molecular Diagnosis

Prior Knowledge Phenotype Associations GWAS Catalog Allele Frequency eQTL Databases Disease Ontology Cancer Genes Prior Cancer Observations Genomic Elements Known Genes Location Relative to Gene Protein Domains Transcription Factor Binding Sites Conserved Elements miRNA Binding Sites miRNA Genes Splice Sites Splicing Enhancers/Silencers Prediction of Impact Coding Impact Nonsynonymous Impact Prediction Protein Domain Impact Prediction TFBS Impact Scores Nucleotide Conservation microRNA BS Impact Splicing Changes Binding Energy Truncation Impact Prediction miRNA Target Changes Linking Elements Phase Information Molecular Function Biological Processes Biological Pathways Synthesis Predicted Disease Variants Predicted Disease Genes …… A solution: Whole Genome Annotation and Prediction genomics.scripps.edu/ADVISER /

Filtered variant of interest: rs

Initial Subject at Scripps: IDIOM Study, Patient #9 Presentation 9-yr-old European female, lifelong history Hypotonia Developmental delays Cognitive impairment Intermittent agitation MRI showed subtle asymmetric volume loss in left hippocampus Motor milestones were delayed Onset of generalized tonic-clonic seizures (GTCS) was at 4.75 years of age Sequencing Quartet exome sequencing WES: SureSelect, 100x coverage, 93-95% with 10+ reads WES Variant Summary: 101,797 SNPs & indels 18,475 Rare variants, <1% allele frequency 1,053 Nonsynonymous, truncating, or splice site 2 De novo inheritance 3 Homozygous or compound heterozygous

Variant files format accepted: VCF, CGI, BED, CNVnator

User accounts and unregistered uploads

Select file to upload

You will receive an once results the file is annotated

SG-ADVISER UI

Load in the annotated SUMMARY file

Loading File – multithreading – progress bar Loads 3GB file in 17 seconds. The scientist can see the first 500 lines and/or see next pages while the file is still loading

12 custom filters

25 category 1 variants

Load genotypes from VCF file

None of the category 1 variants are homozygous, De- novo or compound heterozygous in proband.

IDIOM filter

De novo KCNB1 mutation

Epileptic Encephalopathy

Funding SG-ADVISER, NHGRI 1 U01 HG NIH/NCRR flagship CTSA grant (Eric Topol, MD) Scripps Genomic Medicine Division of Scripps Health Schaeffer Family Foundation / Warren Foundation / Zarrow Foundation Acknowledgements Scripps Translational Science Institute Bill Shipman Ali Torkamani, PhDPhillip Pham

Evening tool demonstrations