Golden Helix s End-to-End Solution for Clinical Labs

Transcription

1 Golden Helix s End-to-End Solution for Clinical Labs Steven Hystad - Field Application Scientist Nathan Fortier Senior Software Engineer 20 most promising Biotech Technology Providers Top 10 Analytics Solution Providers Hype Cycle for Life sciences

2 Questions during the presentation Use the Questions pane in your GoToWebinar window

3 Golden Helix Golden Helix is a global bioinformatics company founded in Variant Calling Filtering and Annotation Clinical Reports CNV Analysis Pipeline: Run Workflows Variant Warehouse Centralized Annotations Hosted Reports Sharing and Integration GWAS Genomic Prediction Large-N-Population Studies RNA-Seq Large-N CNV-Analysis

4 Cited in over 1,100 peer-reviewed publications

5 Over 350 customers globally

6 Golden Helix Who We Are When you choose a Golden Helix solution, you get more than just software REPUTATION TRUST EXPERIENCE INDUSTRY FOCUS THOUGHT LEADERSHIP COMMUNITY TRAINING SUPPORT RESPONSIVENESS INNOVATION and SPEED CUSTOMIZATIONS

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8 Secondary Analysis

9 Why Sentieon? Pipeline Improvements Why Improve Broad s GATK Haplotype Caller? GATK Haplotype Caller is the most accurate DNA analysis tool Problem: GATK Haplotype Caller is too Slow Solution Consistent: No down-sampling or thread dependency = no run-to-run differences = More accurate No Javascript: low level C More Robust: Can handle joint genotyping on over 100K samples simultaneously without needing a gvcf Software-only Solution: Easily deployable, easily scalable, and easily upgraded. Two Product Lines DNAseq BWA-GATK Haplotype Caller Tnseq MuTect and MuTec2

10 Performance: Sentieon vs Broad DNAseq TNseq

11 Proven Accuracy Precision FDA Consistency Challenge - Processed single sample consistency - Single biological sample x two library preps - Top overall performance - Highest reproducibility Truth Challenge - Determine accuracy in Truth Set - Highest indel precision - Highest SNP recall

12 Proven Accuracy - ICGC-TCGA DREAM Mutation Calling Challenge Evaluates Somatic Variant Call Accuracy SNV INDEL Structural Variants Sentieon 98.57% Sentieon 98.14% Sentieon 100% Bina/Roche 97.57% Bina/Roche 97.01% Genowis 99.82% Genowis 96.92% OICR GSI 86.99% Gridss 99.63% Sentieon leads in all categories

13 Customizable secondary pipeline CNV caller Sequencer FASTQ Sentieon BAM Linux VCF -Annotate & filter -Clinical reports

14 CNV and LoH Detection VarSeq Calls CNVs on - Gene Panel Data - Exome Data - Whole Genome Data Faster than CMA and MLPA Utilizes existing coverage data Calls CNVs of every size - Small Single Exon Events - Large Cytogenetic Events

15 CNV Detection via NGS CNVs are called from coverage data Challenges - Coverage varies between samples - Coverage fluctuates between targets - Systematic biases impact coverage Solutions - Data Normalization - Reference Sample Comparison

16 CNV calling in VarSeq Reference samples used for normalization Metrics - Z-score: number of standard deviations from reference sample mean - Ratio: sample coverage divided by reference sample mean - VAF: Variant Allele Frequency For Gene Panels and Exomes - Probabilistic model used to call CNVs - Segmentation identifies large cytogenetic events For Whole Genome Data - Targets segmented using Z-scores - Events called based on Z-score and Ratio thresholds

17 VarSeq Full Clinical Stack

18 VarSeq Suite Flexible Simple VarSeq Scalable Variant annotation, filtering, and interpretation Rich visualizations with GenomeBrowse built-in Powerful GUI and command-line interfaces Repeatable workflows

19 Example Workflows Illumina TruSight Cancer Sequencing Panel - Oncogenes & Tumor Suppressor Genes - Drug Targeting Information & Ongoing Clinical Trials Exome Trio Workflow - Casual Variants Associated with Phenotype - Incidental Findings Hereditary Risk Sequencing Panel - Comprehensive coverage of 175 genes with known associations to inherited cardiac conditions, cancers, and other inherited diseases.

20 Sample Data for Cancer Gene Panels Illumina TruSight Cancer Sequencing Panel - Comprehensive coverage of 154 genes designed to target exons of key tumor suppressor genes and frequently cited oncogenes. - BAM and VCF files for each replicate are available VSReports

21 VarSeq Demonstration

22 Sample Data for Exome Trio Workflows NA year old Caucasian Women - Admitted for Symptoms of Acute Gastroenteritis. - Serum testing revealed elevated pancreatic enzymes. - Genetic testing revealed Heterozygosity for CFTR gene mutation Δ F508 Incidental Findings NA12892 NA12891 NA12878

23 VarSeq Demonstration

24 VSWarehouse Variant Warehouse Server A place to archive full VCFs of every sequenced sample Centralized genomic data hosting, integration with other systems Ask the Variant Warehouse: - Have I ever seen this variant in my previous test samples? - At what frequency? (counts as well) - Does this gene contain other rare variants in my cohort? - Did I provide a pathogenicity assessment for this variant? Has that changed? - Has ClinVar changed since that assessment was initially made? - Have I put this variant into a clinical report for any previous samples?

25 Integration with VarSeq VarSeq can Export to Warehouse - Create a new Project - Current project template is used - Add Variants to Existing (data only) Annotate with Warehouse Counts - Allele / Genotype counts computed on warehouse variants (or other sources in template). Remote Assessment Catalogs - Customize databases of variant classifications or internal flags like false-positives. Remote Reports - Central versioning of report - Queryable database of all saved reports, with all data in form ready for EMR/LIMS integration

26 VSWarehouse Centralized Collaboration Project A Project B VSWarehouse Server Group A Group B Collaborators

27 VSWarehouse Centralized Collaboration

28 VarSeq Full Clinical Stack

29 Questions or more info: Request an evaluation of the software at