1. Cancer genomics, WGS SciLifeLab Human WGS ToolBox Nov 2015 Björn Nystedt, SciLifeLab Bioinformatics platform

2. Why are we here today? 2 Human WGS is becoming routine and will be used both for basic science and for medical discovery and diagnostics SciLifeLab provides multiple resources around Human WGS, which are open to all Swedish researchers The challenges in handling and analyzing Human WGS data calls for collaborations and community knowledge sharing

3. Genomics England 100,000 genomes Overall aims - Advance genomics medicine (integrate into NHS) - Increase research - Boost the private sector in the field The main focus of the program is cancer and rare disease. Huge efforts into setting up the logistics circle. Long-term to transform clinical diagnostics from using sequencing to try to confirm/reject a specific diagnosis, to make a more general match of the patient’s genotype-phenotype profile to a large curated genotype- phenotype space. Goal 100,000 genomes sequenced by the end of 2017 (!)

4. SciLifeLab National service Local scientific center SciLifeLab Director: Olli Kallioniemi Co-director: Lena Claesson-Welsh Vision: To be an internationally leading center that develops, uses and provides access to advanced technologies for molecular biosciences with focus on health and environment. www.scilifelab.se 2010: Strategic research initiative 2013: National resource 2015: New management/chairman 2010: Strategic research initiative 2013: National resource 2015: New management/chairman

5. Human WGS at SciLifeLab Call for National Projects Karin Dahlman- Wright Call for National Projects Karin Dahlman- Wright Computer resources Ola Spjuth/Mart in Dahlö Computer resources Ola Spjuth/Mart in Dahlö Bioinformatic s toolbox Björn Nystedt Bioinformatic s toolbox Björn Nystedt Ethics Richard Rosenquist Ethics Richard Rosenquist The Human WGS Steering Committee Data coordination center Johan Rung Data coordination center Johan Rung Reference database Ulf Gyllensten/A dam Ameur Reference database Ulf Gyllensten/A dam Ameur Sequencing and primary analysis Ellen Sherwood Sequencing and primary analysis Ellen Sherwood SciLifeLab management Clinical Diagnostics NGI (Clinical Diagnostics) Bioinformatics + SNIC (Uppmax) Researcher

6. Human WGS sequencing Oct 2015: $1150, 70 projects, 2300 + 1000 genomes Capacity 5-10,000 genomes/year

7. What is the Human WGS ToolBox? A discussion and coordination forum The bioinformatics platform contributes ~2 FTE to ToolBox implementations Intend to complement current deliveries from the sequencing platform Community building Guidelines Tools Training ToolBox https://wabi-wiki.scilifelab.se/display/SHGATG/

8. What we do right now GATK for hg38 Structural variation: Benchmark, combine tools, compare samples Tumor/Normal/(relapse) somatic variant calling Variant significance tools: Burden tests etc. Some future challenges Epigenetics Time-series designs (Embryo dev, Cell diff, Cell aging) Phased genomes (Imputation, 10X) Integrative designs Single-cell genomics