9/5/2014 for BMI, Stanford University

5. World Health Organization, global burden of neurological disorders estimates and projections, 2014

9. Social deficits
Communication deficits
Repetitive behaviors
•
•
•

15. phenotype
behavior
imaging
genetic

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:

22. ALLENBRAINATLAS

23. ALLENBRAINATLAS

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

31. •
–

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

47.  

48.  

49.  
•
•
•
•
•