2018 NF Conference Cutaneous Neurofibroma Satellite Educational Symposium

1. Developing Therapeutics for Cutaneous
Neurofibromas Symposium
November 2, 2018
Robert Allaway, PhD
Sage Bionetworks
Systems Biology Approaches
to Understanding cNF
Satellite Symposium to the 2018 Joint Global Neurofibromatosis Conference

2. Disclosures
I have no financial relationships to disclose
I will not be discussing off-label or investigational uses of
drugs or devices

3. Project Background
 Pressing questions:
 Key driving molecular components?
 What features define intertumor similarity or
heterogeneity (microenvironment, endocrine,
other)?
 Ideal therapeutic approaches?

4. Project Background
 Pressing questions:
 Key driving molecular components?
 What features define intertumor similarity or
heterogeneity (microenvironment, endocrine,
other)?
 Ideal therapeutic approaches?
 Hurdles for the cNF research
community:
 Only one open dataset with several
comprehensively and genomically characterized
biological samples
 Patients+tumors are very diverse
 ”Quiet” tumors - low mutational burden

5. Project Background
 Pressing questions:
 Key driving molecular components?
 What features define intertumor similarity or
heterogeneity (microenvironment, endocrine,
other)?
 Ideal therapeutic approaches?
 Hurdles for the cNF research
community:
 Only one open dataset with several
comprehensively and genomically characterized
biological samples
 Patients+tumors are very diverse
 ”Quiet” tumors - low mutational burden

6. Project Aims
 Assemble an open-access cNF data
resource with both expression and
mutational data:
 www.synapse.org/cutaneousNF
 Facilitate analysis of these datasets with external
collaborators, help guide users through the
resource

7. Project Aims
 Assemble an open-access cNF data
resource with both expression and
mutational data:
 www.synapse.org/cutaneousNF
 Facilitate analysis of these datasets with external
collaborators, help guide users through the
resource
 Conduct exploratory research of cNF
expression data to better understand the
biology of clinical cNF specimens – 33
specimens from 11 patients
 Pathway analysis (ssGSEA)

8. Recent Results

9. Recent Results

10. Recent Results
• Perform differential expression
analysis for 1 patient vs all other
tumors
• Identify significantly differentially
expressed genes (DEGs) for
each patient
• Then determine overlap of DEGs
across patient

11. Recent Results

12. Challenges and Strategies to
Overcome
 From the computational biology
perspective:
 Quantity of data
 Patient matched controls
 This requires:
 Sharing of 'omic datasets to sufficiently power
studies
 Data with many features require many samples!
 Collaborative research projects to integrate
different data modalities

13. Next Steps and Future Plans
 Extend current exploratory analyses with new
data
 Identify other researchers that could benefit
from the cNF data resource or analyses we
have conducted
 Integrate these data with those being
generated by the NTAP cNF Initiative and other
projects

14. Conclusions and Key Messages
Applying systems biology approaches to
cNF could help…
 guide the direction of future research
 identify new therapeutic targets
 Identify cNF molecular subtypes

15. Conclusions and Key Messages
Applying systems biology approaches to
cNF could help…
 guide the direction of future research
 identify new therapeutic targets
 Identify cNF molecular subtypes
 A large cache of tools and methods already
exists – developed by the cancer systems
biology field
 But to use these methods:
 Need more data via data sharing, or a large
systematic effort to create data, or both

16. Acknowledgements
Annette Bakker, PhD
Salvo La Rosa, PhD
Pamela Knight, MS
Lu Le, MD-PhD
Jean-Philippe
Brousseau, PhD
Hubert Weinberg, MD
Nripesh Prasad, PhD
Sara Gosline, PhD
Justin Guinney, PhD
Xindi Guo, BS
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