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Pre-Proposal Presentation

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Vanessa S
Vanessa S

The document outlines three aims of a research study on autism spectrum disorder: 1) To summarize specific behavioral phenotypes seen in autism as brain maps and sets of associated genes, 2) To validate the brain maps and gene sets using external data from individuals with ASD, and 3) To generate a complex network of genes and behaviors across multiple neuropsychiatric disorders and functionally annotate the results.

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Pre-Proposal Presentation
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World Health Organization, global burden of neurological disorders estimates and projections, 2014
Pre-Proposal Presentation
Pre-Proposal Presentation
Pre-Proposal Presentation
Social deficits Communication deficits Repetitive behaviors • • •
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Pre-Proposal Presentation
Pre-Proposal Presentation
Pre-Proposal Presentation
Pre-Proposal Presentation
phenotype behavior imaging genetic
Pre-Proposal Presentation
• Aim 1: To summarize specific behavioral phenotypes as brain maps and gene sets • Aim 2: To validate brain maps and behavior-gene sets using external data from individuals with Autism Spectrum Disorder • Aim 3: To generate a complex network of genes and behaviors across multiple neuropsychiatric disorders, and functionally annotate this result
Aim 1 To summarize specific behavioral phenotypes as brain maps and gene sets
What does the neuroscience literature have to say about the experience of anxiety??: A: 1 0 1 0 0 0 2 1 0 1 0 1 3 0 0 0 0 1 4 1 0 0 0 1 5 0 1 1 0 0 6 0 0 0 0 0 7 0 1 0 1 1 STUDIES VOXEL COORDINATES NEUROSYNTH
What does the neuroscience literature have to say about the experience of anxiety??: NEUROSYNTH A:
Pre-Proposal Presentation
ALLENBRAINATLAS
ALLENBRAINATLAS
Sample 1 Sample 2. . Sample N genes 1.. 60K 0.25 .012 1.20 … … … 1.50 0.80 3.40 … … … 0.80 0.90 1.00 … … … 0.40 .075 0.20 … … … 1.40 0.32 4.50 … … … 0.89 0.21 2.40 … … … 0.70 0.10 1.20 … … …
• • Bigger change = more “important”
• • R2 % variance accounted for by model quality of model predictors
• R2 with attribute j R2 without attribute j Shapley value of gene j weight based on n total Predictors, k in model
• marginal contribution to the R2 from adding the attribute to the model last
0 0 0 0 1 0 1 0 1 0 0 0 1 0 0 0 0 0 0 0 1 • • 0.25 0.12 1.20 1.50 0.80 3.40 0.80 0.90 1.00 0.40 0.75 0.20 1.40 0.32 4.50 0.89 0.21 2.40 0.70 0.10 1.20 1 0 1 0 0 0 0 0 0 0 1 0 0 0 0 1 0 1 0 0 0
Aim 2 To validate brain maps and behavior-gene sets using external data from individuals with Autism Spectrum Disorder
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Subramanian, et. al, Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles. PNAS 2005 102 (43) 15545-15550; published ahead of print September 30, 2005,doi:10.1073/pnas.0506580102
Pre-Proposal Presentation
Pre-Proposal Presentation
Pre-Proposal Presentation
Pre-Proposal Presentation
Pre-Proposal Presentation
Pre-Proposal Presentation
Aim 3 To generate a complex network of genes and behaviors across multiple neuropsychiatric disorders, and functionally annotate this result
Pre-Proposal Presentation
Pre-Proposal Presentation
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Pre-Proposal Presentation

  • 5. World Health Organization, global burden of neurological disorders estimates and projections, 2014
  • 17. • Aim 1: To summarize specific behavioral phenotypes as brain maps and gene sets • Aim 2: To validate brain maps and behavior-gene sets using external data from individuals with Autism Spectrum Disorder • Aim 3: To generate a complex network of genes and behaviors across multiple neuropsychiatric disorders, and functionally annotate this result
  • 18. Aim 1 To summarize specific behavioral phenotypes as brain maps and gene sets
  • 19. What does the neuroscience literature have to say about the experience of anxiety??: A: 1 0 1 0 0 0 2 1 0 1 0 1 3 0 0 0 0 1 4 1 0 0 0 1 5 0 1 1 0 0 6 0 0 0 0 0 7 0 1 0 1 1 STUDIES VOXEL COORDINATES NEUROSYNTH
  • 20. What does the neuroscience literature have to say about the experience of anxiety??: NEUROSYNTH A:
  • 24. Sample 1 Sample 2. . Sample N genes 1.. 60K 0.25 .012 1.20 … … … 1.50 0.80 3.40 … … … 0.80 0.90 1.00 … … … 0.40 .075 0.20 … … … 1.40 0.32 4.50 … … … 0.89 0.21 2.40 … … … 0.70 0.10 1.20 … … …
  • 25. • • Bigger change = more “important”
  • 26. • • R2 % variance accounted for by model quality of model predictors
  • 27. • R2 with attribute j R2 without attribute j Shapley value of gene j weight based on n total Predictors, k in model
  • 28. • marginal contribution to the R2 from adding the attribute to the model last
  • 29. 0 0 0 0 1 0 1 0 1 0 0 0 1 0 0 0 0 0 0 0 1 • • 0.25 0.12 1.20 1.50 0.80 3.40 0.80 0.90 1.00 0.40 0.75 0.20 1.40 0.32 4.50 0.89 0.21 2.40 0.70 0.10 1.20 1 0 1 0 0 0 0 0 0 0 1 0 0 0 0 1 0 1 0 0 0
  • 30. Aim 2 To validate brain maps and behavior-gene sets using external data from individuals with Autism Spectrum Disorder
  • 32. Subramanian, et. al, Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles. PNAS 2005 102 (43) 15545-15550; published ahead of print September 30, 2005,doi:10.1073/pnas.0506580102
  • 39. Aim 3 To generate a complex network of genes and behaviors across multiple neuropsychiatric disorders, and functionally annotate this result