1. IBIC Summer Retreat Allen Institute Human Brain Atlas Allan R. Jones, PhD Chief Scientific Officer June 7, 2009

2. 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

3. 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)

4. 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

5. Human Brain Atlas Overview: 2008-2012 Multimodal atlas integrating gene expression and neuroanatomy Phase 1: Anatomic resolution atlas All structures: Comprehensively sample human brain All genes: Microarray and sequence-based gene expression profiling Phase 2: Cellular resolution atlas Most structures: High-resolution atlas of each structure High-value genes: ISH for 50-500 genes/structure PlanningPhase 1: Microarray Data 20082009201020112012 PlanningPhase 2: ISH data Protocol v 0.5 Status Check Initial data releaseProject completion

6. (Fresh brain images courtesy Mark Vawter and Preston Cartagena) Section 1 mm of slab Whole brain to microarray: serial divisions Whole brain 5 mm coronal slabs Full coronal histology Subdivide slab into 2x3 blocks (subset of ~60 structures) Nis sl Myel in IHC ISH Nis sl Myel in IHC LCM subcortex cortex Cryosection through 3 mm of 2x3 blockFinal 1 mm of block gross dissection 1 cm sampling 0.5 cm sampling MRI ~700 cortical samples ~300 subcortical samples

7. 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) (a) (d) (b)(c) (e) (f) (g)(h) (i) (j)

8. Human Atlas Analysis and Visualization Applications