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

Social deficits Communication deficits Repetitive behaviors

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phenotype

behavior

imaging

genetic

• 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

STU

DIE

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VOXEL COORDINATES

NEU

RO

SYN

TH

What does the neuroscience literature have to say about the experience of anxiety? ?: N

EUR

OSY

NTH

A:

ALLEN

BR

AIN

ATLA

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ALLEN

BR

AIN

ATLA

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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 … … …

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Bigger change = more “important”

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R2

% variance accounted for by model quality of model predictors

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R2 with attribute j

R2 without attribute j

Shapley value of gene j

weight based on n total Predictors, k in model

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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

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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

Aim 3

To generate a complex network of genes and behaviors across multiple neuropsychiatric disorders, and functionally annotate this result

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