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Reproducible	Genomic	Interpretation	
Tools	for	Translational	Medicine:	
Application	to	an	N	of	1	Case	Study
Kathleen	Fisch...
Outline
2/20
• Translational	Medicine	
• Precision	oncology
• Immunotherapy
• Neoantigen discovery
• N	of	1	Case	Study:	Uv...
Translational	Medicine	– Precision	Oncology
3/20
Arnedos et	al.	2015
Translational	Medicine	– Immunotherapy
4/20
Smith	&	Housseau 2015
Translational	Medicine	– Neoantigen Discovery
5/20
Schumacher	&	Schreiber	2015	Science
N	of	1	Case	Study:	Disease	Etiology
6/20
Uveal	Melanoma
N	of	1	Case	Study:	Disease	Etiology
7/20
Blum	et	al.	2016	Oncology
N	of	1	Case	Study:	Patient	Background
8/20
Female,	Caucasian,	mid-50s
Blood	
Tumor
Whole	Genome	Sequencing
RNA	sequencing
...
N	of	1	Case	Study:	Motivation
1. Characterize	molecular	
landscape	of	the	patient’s	tumor
2. Identify	prognostic	markers
3...
N	of	1	Case	Study:	Analysis	Workflow
10/20
Tumor	RNA-seq
Tumor	Targeted	
DNA-seq
Blood
WGS
Gene	
Expression	
Profiling
Som...
N	of	1	Case	Study:	Subtype	Stratification
11/20
N	of	1	RNAseq subtype	stratification	with	TCGA	Uveal	
Melanoma	Cohort
Clas...
N	of	1	Case	Study:	Pathogenic	Variants
12/20
GNAQ	p.Q209L SF3B1	p.R625H BAP1	p.G41S
somatic germline somatic
Patient	Tumor...
N	of	1	Case	Study:	Candidate	Tumor	Neoantigens
13/20
EFHC1
LAMB2
ECSIT
MTDH
ABCB5
HLA-A02:01
N	of	1	Case	Study:	Network	Analysis
14/20
Legend
Red:	High	gene	expression
Orange:	Moderate	gene	expression
Green:	Low	gen...
Jupyter-Genomics	– Overview
15/20
https://github.com
/ucsd-ccbb/jupyter-
genomics
Jupyter-Genomics	– Available	Workflows
16/20
NGS	Analysis	with	CFN	cluster
Variant	Annotation	 &	Filtering
Microbiome
Cris...
Jupyter-Genomics	–
Translational	Medicine	Workflow
17/20
Jupyter-Genomics	– Deployment
18/20
ami-f04fb690
Future	Directions
• Additional	Jupyter-Genomics	workflows
• Translational	medicine
• Biological	interpretation
• Data	visu...
Acknowledgements
20/20
Contact:	Katie	Fisch		Kfisch@ucsd.edu
Website: compbio.ucsd.edu
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ISMB Translational Medicine SIG 2016: Reproducible Genomic Interpretation Tools for Translational Medicine: Application to an N of 1 Case Study

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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).

Published in: Science
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ISMB Translational Medicine SIG 2016: Reproducible Genomic Interpretation Tools for Translational Medicine: Application to an N of 1 Case Study

  1. 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. 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. 3. Translational Medicine – Precision Oncology 3/20 Arnedos et al. 2015
  4. 4. Translational Medicine – Immunotherapy 4/20 Smith & Housseau 2015
  5. 5. Translational Medicine – Neoantigen Discovery 5/20 Schumacher & Schreiber 2015 Science
  6. 6. N of 1 Case Study: Disease Etiology 6/20 Uveal Melanoma
  7. 7. N of 1 Case Study: Disease Etiology 7/20 Blum et al. 2016 Oncology
  8. 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. 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. 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. 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. 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. 13. N of 1 Case Study: Candidate Tumor Neoantigens 13/20 EFHC1 LAMB2 ECSIT MTDH ABCB5 HLA-A02:01
  14. 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. 15. Jupyter-Genomics – Overview 15/20 https://github.com /ucsd-ccbb/jupyter- genomics
  16. 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. 17. Jupyter-Genomics – Translational Medicine Workflow 17/20
  18. 18. Jupyter-Genomics – Deployment 18/20 ami-f04fb690
  19. 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. 20. Acknowledgements 20/20 Contact: Katie Fisch Kfisch@ucsd.edu Website: compbio.ucsd.edu

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