IBIC Summer RetreatAllen Institute Human Brain Atlas

Allan R. Jones, PhD

Chief Scientific Officer

June 7, 2009

Allen Institute for Brain Science: Fueling Discovery

• Who/what we are:– An independent, non-profit research organization working to support basic research in

the brain sciences (founded in 2001).

– Dedicated to making tools and information readily available to the scientific community

– Project-focused, milestone driven

– Multi-disciplinary teams working towards a common goal (math, physics, engineering, systems-level and molecular neuroscience, molecular biology, genetics, genomics, information technology)

– ~120 staff (30 PhDs)

– Located in 35000 sf of mixed lab/office space in the Fremont neighborhood of Seattle Washington

• What we are not:– A traditional, PI-driven research organization

– An extramural funding agency

The Allen Institute for Brain Science: Tools, resources, and data

Atlases: •Adult mouse brain (complete Sept. 2006)

•Mouse spinal cord (complete April 2009)

•Mouse development (complete March 2010)

• Human brain

•Phase 1 complete mid-2010

•Phase 2 complete in 2012

Projects:

•Sleep study (complete Dec. 2007)

•Genetic diversity study (complete May 2008)

• Human cortex survey (complete Sept. 2008)

•Human cortex population study/schizophrenia (complete Jan. 2009)

•Human Glioblastoma (complete April 2011 with possible extension)

Tools:

•Transgenic mouse drivers/reporters

•~20,000 unique visits per month across all projects (65% mouse brain, 10% human cortex, 10% development, 10% spinal cord, 5% sleep)•Atlas paper has been cited 260 times since publication in January 2007 (validation, discovery)

Connecting the “what” to the “where”

• We are quickly approaching a renaissance in our understanding of the basic genetic underpinnings of human biology and behavior

– Technology has enabled easy, cheap access to high resolution genetic data from humans. Large scale studies are underway

– Technology has provided ways to link functions in the brain to location

• Researchers that study genetics of human behavior and brain disease will be able to identify key genes

• Researchers that study brain function can already pinpoint brain locations that are altered or perform aberrantly in disease

• A key resource is needed to tie the “functional” maps with the “genetic” maps: a gene expression map of the human brain

Human Brain Atlas Overview: 2008-2012Multimodal atlas integrating gene expression and neuroanatomy

Phase 1: Anatomic resolution atlasAll structures:Comprehensively sample human brain

All genes:Microarray and sequence-based gene expression profiling

Phase 2: Cellular resolution atlasMost structures:High-resolution atlas of each structure

High-value genes: ISH for 50-500 genes/structure

Planning Phase 1: Microarray Data

2008 2009 2010 2011 2012

Planning Phase 2: ISH data

Protocol v 0.5 Status Check Initial data release Project completion

(Fresh brain images courtesy Mark Vawter and Preston Cartagena)

Section 1 mm of slab

Whole brain to microarray: serial divisionsWhole brain 5 mm coronal slabs Full coronal histology

Subdivide slab into 2x3 blocks

(subset of ~60 structures)

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IHC

IHCIH

CIH

CIS

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subcortex

cortex

Cryosection through 3 mm of 2x3 block Final 1 mm of block

gross dissection

1 cmsampling

0.5 cmsampling

MRI

~700 cortical samples

~300 subcortical samples

Macro-dissection (cortex)

2-10 human brain specimens

5 mm coronal slabs

Blockface images

6x8 histology, 2x3 histology, immunohistochemistry and in situ

hybridization (ISH)

Subdivided slab 2x3 blocks

Anatomic segmentations

User applications

MRI and DTI

Microarray analysis

LCM (sub-cortex)

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Human Atlas Analysis and Visualization Applications