TransMed 2016 SIG presentation for ISMB 2016 in Orlando, Florida (https://www.iscb.org/ismb2016program/ismb2016-sigs#transmed) profiling a precision medicine case study and open source notebooks developed for translational medicine (Jupyter-Genomics https://github.com/ucsd-ccbb/jupyter-genomics).

1. Reproducible Genomic Interpretation
Tools for Translational Medicine:
Application to an N of 1 Case Study
Kathleen Fisch, Ph.D.
Department of Medicine, Center for Computational Biology &
Bioinformatics, University of California, San Diego, La Jolla, CA, USA

2. Outline
2/20
• Translational Medicine
• Precision oncology
• Immunotherapy
• Neoantigen discovery
• N of 1 Case Study: Uveal Melanoma
• Disease etiology
• Patient background/motivation
• Analysis workflow
• Pathogenic variants, subtype stratification & candidate tumor neoantigens
• Genomic interpretation workflows for translational medicine – Jupyter-Genomics
• Overview
• Available workflows
• Deployment
• Future directions

3. Translational Medicine – Precision Oncology
3/20
Arnedos et al. 2015

4. Translational Medicine – Immunotherapy
4/20
Smith & Housseau 2015

5. Translational Medicine – Neoantigen Discovery
5/20
Schumacher & Schreiber 2015 Science

6. N of 1 Case Study: Disease Etiology
6/20
Uveal Melanoma

7. N of 1 Case Study: Disease Etiology
7/20
Blum et al. 2016 Oncology

8. N of 1 Case Study: Patient Background
8/20
Female, Caucasian, mid-50s
Blood
Tumor
Whole Genome Sequencing
RNA sequencing
Targeted DNA sequencing

9. N of 1 Case Study: Motivation
1. Characterize molecular
landscape of the patient’s tumor
2. Identify prognostic markers
3. Identify tumor neoantigens for
immunotherapy
99/20

10. N of 1 Case Study: Analysis Workflow
10/20
Tumor RNA-seq
Tumor Targeted
DNA-seq
Blood
WGS
Gene
Expression
Profiling
Somatic
Mutations
Prognostic
Subtyping
RNA
variants
Tumor
variants
Germline
variants
Candidate
Neoantigens
Prognostic Variants
TCGA cohort
normalization
Network
Analysis

11. N of 1 Case Study: Subtype Stratification
11/20
N of 1 RNAseq subtype stratification with TCGA Uveal
Melanoma Cohort
Class 2
Tumors
Class 1
Tumors
Normalized TCGA Cohort
Patient Sample

12. N of 1 Case Study: Pathogenic Variants
12/20
GNAQ p.Q209L SF3B1 p.R625H BAP1 p.G41S
somatic germline somatic
Patient Tumor Mutation Profile

13. N of 1 Case Study: Candidate Tumor Neoantigens
13/20
EFHC1
LAMB2
ECSIT
MTDH
ABCB5
HLA-A02:01

14. N of 1 Case Study: Network Analysis
14/20
Legend
Red: High gene expression
Orange: Moderate gene expression
Green: Low gene expression
Blue Star: Germline variant
Yellow Star: Somatic variant
Network of UVM genes depicting relationships, relative gene expression and variants.

15. Jupyter-Genomics – Overview
15/20
https://github.com
/ucsd-ccbb/jupyter-
genomics

16. Jupyter-Genomics – Available Workflows
16/20
NGS Analysis with CFN cluster
Variant Annotation & Filtering
Microbiome
Crispr
Network Analysis
Translational Medicine
Gene Expression Profiling

17. Jupyter-Genomics –
Translational Medicine Workflow
17/20

18. Jupyter-Genomics – Deployment
18/20
ami-f04fb690

19. Future Directions
• Additional Jupyter-Genomics workflows
• Translational medicine
• Biological interpretation
• Data visualization
• Invite community contributions
• Continue working with the UVM patient
and other N of 1 cases to guide
development and improve patient
outcomes
19/20

20. Acknowledgements
20/20
Contact: Katie Fisch Kfisch@ucsd.edu
Website: compbio.ucsd.edu