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Kymberleigh Pagel Karchin Lab

Getting started: Installation, submission, and viewing results. Kymberleigh Pagel Karchin Lab Department of Biomedical Engineering Institute of Computational Medicine Johns Hopkins University. https:// opencravat.org. @OpenCRAVAT. C ustom R anked A nalysis of Va riants T oolkit.

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Kymberleigh Pagel Karchin Lab

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  1. Getting started: Installation, submission, and viewing results Kymberleigh Pagel Karchin Lab Department of Biomedical EngineeringInstitute of Computational Medicine Johns Hopkins University https://opencravat.org @OpenCRAVAT

  2. Custom Ranked Analysis of Variants Toolkit Variant Analysis is important to tackling genetic disease • Addresses the gap between the amount of available data and our ability to harness and incorporate that information. • Platform for sharing and integration of genetic annotations • Developers and curators can provide data directly to users • Open source and locally installable Genomic Features Annotations Machine Learning Algorithms

  3. CRAVAT

  4. Framework components 1. Select and download modules 2. Input variant file(s) 3. Submit for processing 4. Filter and analyze 5. Export and share results Single Sample Cohort

  5. Example use case Identify early candidate driver mutations in an ovarian cancer patient, using VCF and BAM files from a published genomic study of high-grade serous ovarian cancers Labidi-Galy, S. Intidhar, et al. "High grade serous ovarian carcinomas originate in the fallopian tube." Nature communications 8.1 (2017): 1093.

  6. Example pipeline overview Right ovarian tumor Left ovarian tumor Submit to OpenCRAVAT Reference Genome and input VCFs Select and download modules Job submission Filter Application Data Exploration Allele frequency Appendiceal metastasis Driver gene filter Omental metastasis Mutation consequence types Mutation quality (filter, reads) Explore results Export and share Load BAM and visualize with IGV Rectal metastasis Left Fallopian STIC, P53 signature Sequence data have been deposited at the European Genome-phenome Archive, which is hosted at the European Bioinformatics Institute, under study accession EGAS00001002589.

  7. Installation Install via downloadable package or Pip (Python 3.6) Command line and GUI implementation packaged together Mac, Ubuntu, Windows Local installation preserves privacy, server and cloud versions coming soon pip install open-cravat cravat-admin install-base On terminal:

  8. Selecting annotations from the store

  9. OpenCRAVAT “store”

  10. Installing modules from the store

  11. Types of modules in the store Input formats Annotations Output formats • Population databases • Computational predictions • Multiplex assays • Literature • Genomic elements • Noncoding • Clinical relevance • Interactions • Visualization VCFTSV dbSNP IDs* Ancestry* 23&Me* GUI Excel TXT CSV* VCF* Converters Reporters Annotators

  12. Select relevant modules from the store

  13. Installing modules from the store Weekly store growth External developers can contribute and publish to store cravat-admin install clinvar

  14. Installing modules from the store Short description Data version Point of contact Citation Website • Developer’s dream

  15. Submitting a job

  16. Screenshot of submission process Jobs table Submission pane

  17. Screenshot of submission process Choose input Input formats VCF, TSV, 23Me, Ancestry dbSNP identifiers

  18. Screenshot of submission process For each job, select your preferred annotators Choose input Select annotations

  19. Screenshot of submission process Choose input Select annotations Submit for processing cravat <input file> -t text

  20. Launch the Graphical User Interface Open Viewer Download files cravat-view input.sqlite

  21. Filter Summary Variant Gene Interactive Viewer

  22. Tabbed navigation

  23. Summary page

  24. Filter Filter based upon presence in individual samples. Filter

  25. Gene list Variant properties Filter by gene and variant characteristics

  26. Query builder for advanced and complex filters Fully customizable filter options

  27. Variant tab Variant table Widgets (describe the selected variant)

  28. Variants displayed as rows in an annotation table

  29. Variant tab includes alternative isoforms

  30. Click header to sort by value Hover cursor over headers to learn more Table view is dynamic and interactive Search function Displays selected cell contents

  31. Widgets summarize and visualize key information

  32. Widgets for visualization

  33. Links out to MuPIT for 3D protein and variant visualization Visualization widgets

  34. Gene tab

  35. Click to save layout and filter settings Customize and save interface preferences Expand and collapse fields with multiple columns Right click to hide some (or all) columns per annotation Re-order the interface by dragging individual columns left/right

  36. Summary • OpenCRAVAT reduces the barrier to perform high-throughput analysis of genetic variation • An open source platform for sharing and integration of genetic annotations • Custom configuration of workflows, interface, and sharable output files • Locally installable – designed for all levels of computational expertise

  37. Principal Collaborators and Funding for the Project Karchin Lab Rachel Karchin NoushinNiknafs Collin Tokheim Chris Douville Lily Zheng In Silico Solutions Michael Ryan Rick Kim Kyle Moad Other collaborators: Ben Busby Christian Townes Funding for OpenCRAVAT/MuPIT Information Technologies for Cancer Research, NCI (grants U01-CA180956, U24CA204817) support@cravat.us http://opencravat.org @OpenCRAVAT

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