Bioinformatics Core

1. Nicholas D. Socci, PhD Bioinformatics Core

2. Services and Technologies EDUCATION & TRAINING OFFERED ANALYSIS PROVIDED Data analysis applications/pipelines DNA/Variant Detection DNA/Copy Number RNA-seq/Differential Expression Custom programming Bioinformatic pipelines Clinical database applications Expansion: Platform Informatics Group • Scientific consultations & clinics • Weekly open sessions • Bioinformatics onboarding • Consultation support for laboratory staff • Workshops & training • Courses include R, bioinformatics, and programming • Develop new offerings in collaboration with VP of Scientific Education

3. Location STAFF COMPUTE Local server rooms to support IGO operations are located in the Zuckerman Research Center (ZRC): ZRC 3rd floor ZRC C2 The main high performance computing clusters are located in the New Jersey Data Center • The offices for the Bioinformatics Core staff are located in the Zuckerman Research Center (ZRC): • Administration/Consultations: 11th floor • Engineering, programming, and high performance computing staff: 4th floor • Expansion: • Platform Informatics Group: 3rd floor

4. Research Supported Molecular Determinants of Response to Anti–Programmed Cell Death (PD)-1 and Anti–Programmed Death-Ligand 1 (PD-L1) Blockade in Patients With Non–Small-Cell Lung Cancer Profiled With Targeted Next-Generation Sequencing J ClinOncol 2018 • Arcila (CR), Berger (CBEP), Chaft (CR), Halpenny (CR), Hellmann (CR), Kris (CR), Ladanyi (CBEP, CR), Plodkowski (CR), Riely (CR), Rudin (ET, CR), Schultz (CBEP, CR), Shen (CR, PSR), Snyder (CR), Solit (ET, CR), Taylor (CBEP), Wolchok (IT, CR) • Tumor mutation burden (TMB) predicative of efficacy of immuno-therapy • Targeted sequencing can accurately measures TMB • Copy number complexity inversely correlated with TMB and outcome • Core’s contribution • Optimized pipeline for WES analysis

5. Research Supported PGBD5 promotes site-specific oncogenic mutations in human tumors. Nat Genet. 2017 • Antonescu (CBEP, CR), Kentsis (GI, ET) • Transposition events underlie childhood tumors; majority express PGBD5 • Rearrangements involving PGBD5 inactivate tumor suppressors • PGBD5 associated with specific signal sequences • Core’s contribution: • Developed and ran optimized pipeline for mapping whole genome sequence data: BAM-deliverable • Installed/configured custom software for use by lab bioinformatics staff BAM FASTQ

6. Research Supported Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity Nat Biotech 2016 • Schultz (CBEP, CR), Solit (ET, CR), Taylor (CBEP) • Develop methods to statistically assess significance at residue (instead of gene) level • 243 novel hotspots identified • Coupling of mutant allele specificity and linage diversity • Core’s contribution • Statistical analysis • Computational consultation/support

7. Research Supported Inducible in vivo genome editing with CRISPR-Cas9 Nat Biotech 2015 • Lowe (CBEP) • Designed conditional transgenic model using inducible CRiSPR-Cas9 • Allows temporal control of genome editing • Can target multiple loci • Core’s contribution: • Custom pipeline development • Exhaustive enumeration • All mutation (indels) events • Potential off target regions

8. Research Supported A recurrent neomorphic mutation in MYOD1 defines a clinically aggressive subset of embryonal rhabdomyosarcoma associated with PI3K-AKT pathway mutations Nat Genet 2014 • Ladanyi (CBEP, CR), Meyers (CR), Qin (CR), Reis-Filho (CBEP), Shukla (CR), Singer (CR), Wexler (CR) • Embryonal Rhabdomyosarcoma (ERMS) lack x-FOXO1 fusion seen in other RMS subtypes • Whole exome sequencing revels recurrent mutations in MYOD1 for a subset of ERMS (p.L122A) • Mutated MYOD1 binds MYC consensus activating similar expression program • Core’s contribution: • Standard pipelines for exome variants/RNA-seq • Proto-type pipeline for RNA-variant detection Mouse Human

9. Usage and Productivity Non Peer-Reviewed* • Usage (7/16-6/17) • 94 Investigators • 10 CCSG Programs • Scientific Productivity (1/14-6/17) • 889 Publications Peer-Reviewed * Includes newly-recruited junior faculty

10. Current and Proposed Budgets CCSG CCSG Other* 16% Other* 26% 31% Chargebacks Chargebacks 58% 56% 87% of users are peer-reviewed; 27% of the proposed budget is requested from the CCSG. *Other = Institutional Support

11. Value Added Standardized & reproducible analyzes Knowledge transfer Assist and support growing group of bioinformatics staff/researchers The core supports all 10 program projects. • Develop, maintain, implement computational critical pipelines • Stop researcher from reinventing them • Provide a repository of reusable component • Programming staff can assist in customization • Develop specific methods for individual research questions

12. Future Plans Technology R&D Research Support Design & implement tools for self-analysis Micro-portals Continue to support and collaborate with the growing number of bioinformatics researchers New training courses Technology sharing • Pipeline development • Image analysis • Single cell [expand] • Migrate to Cloud Computing • Implement database application for clinical research