Where we’ve been, Where we’re going

Arthur TogaLaboratory of Neuro Imaging, UCLA

Goals

Digital Atlases

Integrate Gene Expression Efforts

Automated Image Processing

Integrated Interface Applications

Focus on:

Neurodegenerative Diseases

Tools to share and mine multi-scale structural and functional mouse brain data

Data Integration Framework

2. Create conceptual links to a shared ontology

1. Create multimodal databases

3. Situate the data in a common spatial framework

4. Use mediator to navigate and query across data sources

Grid infrastructure

Upload Discover Access Collaborate

Upload scripts

Human Imaging DB

Spatial registry

BIRNLex

Animal Imaging DB

Organize Analyze

Provenance management

Performance improvements, better error handling, utilization of authentication resources,

integration of application services with ROCKS, BIRN authentication, portal via application launcher…

FAQs, tutorials, API

registry, collaborative programming

tools.

Morphometric analysis

Microarray analysis

Atlas Interoperability server and API

status

Replication services

Oracle upgrade

SRB upgrade

Distributed MCAT

Mediator

WS-XCEDE

WS

Upload client

Data Quality Assurance,

specific for data classes

Atlas and Query tools: Concept-based query,

view-based query

Global search

FIPS: grid-basedAnnotation tools

FreeSurfer, 3D Slicer

LONI Pipeline

integration

Workflow management

integration

Better compute grid access

Data publication standards

Command-line data access

Portal

Databases

WS-XCEDE

CCDB

WS

WS

Registration workflows:

Clinical/behavioralMR scannerMR (FBIRN)Microarray

Microscopy/atlas data (2D, 3D…)

ontologies

WS

Registration portlets

WS-XCEDEWS

Subject IDs generator

Project IDs generator

WS

WS

ID assignmentportlets

Projects DB

Subjects DB

Subject ID mapper

Project ID mapper

status

Global search portlet

: web service interface : high priority

Respective portlets

Database backup

Datagrid:

Computegrid:

Integrate

Data serve and download (e.g. for

large images)

WS

Annotation interfaces

Data integration services: terms

mapping

MBAT/WOMBAT; query interfaces

Tools accessed from portal; Eclipse

Workflow Client

SRB URIs collection

management

XCEDE 2.0

Improved data security

DB schemas and GUI (portal dashboard),

versioning and regression tests (HID)

DB dashboardsand backup

Image QA ongrid (+curation

dashboard)Microarray DB

WSO

ther

DB

s

Find commonalitiesAdjust to AIDB,MADB

XNAT

BIRN Roadmap

Upload

Mouse Tools for Data Upload and Registration (Compatible with BIRNLex): – Microarray GE registration (Q1: UCLA, UTHSC)

• Also Compatible with MAGE (Standard Microarray XML data exchange format)

– 2D image registration (Q1: UCSD/CC) • Also Compatible with 3D data used by other groups

– 3D MR upload (Q1) and preprocessing (Q3) • (Duke, UCLA, Caltech)• Also Compatible with XCEDE (Human BIRN XML-based image and

event data descriptors)

Completed: – CCDB-Production Version for Upload (UCSD)– 2D Spatial Registration (UCSD)– 3D MR Upload Tools Local Versions (Duke, UCLA)– Microarray Beta Version (UCLA, UTHSC)

Database Expansion for Upload and Query

Compatible with BIRNLex– CCDB:

• Expand Web-Services for MBAT query (Q1: UCSD, UCLA)– Also Compatible with Atlas Interoperability Server and API

• Finish Version for Upload to New BIRN Portal (Q1: UCSD, CC)– BIRN Microarray Database and GeneNetwork:

• Publicly Available Production Database (Q1: UCLA, UTHSC, Drexel, CC)

– Also Compatible with MAGE– ArcIMS:

• Create Web-Services for MBAT query (Q2: CC, UCSD, UCLA)– Animal Imaging Database (AIDB):

• Implement Beta Version of Database (Q3: CC and All Mouse)– Also Compatible with XCEDE and Atlas Interoperability Server and API

Completed: – CCDB First Version of Web-Services (UCSD)– BIRN Microarray Development Database (UCLA, UTHSC)– Specifications for Migration of BIRN Microarray Databases to Production

(UCLA, UTHSC, Drexel, CC)

External Datasets/Databases for MBAT Access

Microarray: – Genomics Institute of the Novartis Research Foundation (GNF)

(Q1: UTHSC, UCLA)– NIH Microarray Consortium (Q3: UTHSC, UCLA)

Other:– GENSAT: queryable database from groups outside of GENSAT

(Q3: Drexel, UCLA, UCSD)– MousePat for Gene Expression Profiling and Mapping, a

Visualization system for Gene Expression Profiling and Mapping from ICS-MCI (Institut Clinique de la Souris and Mouse Clinical Institute) (Q3: UCLA, CC, UCSD)

Completed: – Test Uploads of GNF to BIRN Microarray DB (UTHSC, UCLA)– Preliminary Work with Groups creating Queryable GENSAT

databases (Drexel, UCLA)

MBAT for Intuitive Discovery and Access to Databases

MediatorMediator

Discovery: Mouse BIRN Query

Beta Version Mouse BIRN Global Concept-Based Query (Q1: UCLA, All Test-beds)

– Will be implemented in MBAT/WOMBAT– Build so it may be implemented in portlet or by Human BIRNs– Compatible with BIRNLex and Mediator

Test Version View-Based Spatial Query in MBAT/WOMBAT (Q2: UCLA, UCSD, All Mouse)

– Compatible with Atlas Interoperability Server and API

Test Version BIRN Ontology Query (BonFire/BIRNLex) in MBAT/WOMBAT (Q2: CC, UCSD, UCLA)

Completed: – Interface for Simultaneous Multiple Data Source Microarray Query (UCLA,

UTHSC, CC)– Interface for Filtering Microarray Query Results (UCLA)– Generate Queries to Mediator (CC, UCLA)– View-Based Spatial Query Tools in SmartAtlas (UCSD)– Specifications for Global Conceptual Query User Interface (UCLA)– Beta Versions of BonFire Query Tools (CC/UCSD, UCLA)

Discovery and Access (DA) from MBAT

Compatible with BIRNLex and Atlas Interoperability Server/API – Implement Ability to Discover and Access NeuroTerrain and

registered MBL data (Q2: Drexel, UCLA, UCSD)– Implement Ability to Discover and Access registered CCDB datasets

from new database (Q1: UCSD, UCLA)– Implement Ability to Discover and Access 2D datasets from ArcIMS

(Q3: CC, UCSD, UCLA)

Completed: – Refactoring and Extension of NeuroTerrain Server for Mouse BIRN

(Drexel)– Release of NT-SDK for integration of NeuroTerrain in JAVA (Drexel)– Test Implementations of NT-SDK and NeuroTerrain framework in

other Mouse Tools (Drexel, UCSD, UCLA)– Initial Testing of CCDB web-services (UCSD, UCLA)

Expand MBAT/WOMBAT Functionality for Discovery and Access

MediatorMediator

Microarray DB

NeuroTerrain and MBL

ArcIMS

CCDB

Integration Work

Atlas Server and Interoperability API: – Finish Test Implementation for use by our Groups (Q2: UCSD, UCLA, Drexel) – Begin Testing with Outside Groups (Q4: All Mouse, All test-beds)

Completed: – API Implemented for Atlas Interoperability (UCSD, Drexel)– Test Transformation from MBAT Atlases to Paxinos (UCLA, UCSD)– Transformation on Database and Accessible through web-services (UCSD)– Creation of Demo using this Framework for the AHM (UCSD, UCLA)

Mediator:– Connect to other Mouse Databases using Mediator (Q2: CC, UCLA, All Mouse)– Implement Dynamic and more Complex and Queries (Q3: CC, All Mouse)– Map Site DBs with New Mediator Tools (Q2: CC, All Mouse)

Completed: – Accessing Microarray data on BIRN Databases with Mediator (CC, UCLA)

Integration Work

BIRNLex:– Add Terminology for:

• Inter-Atlas Anatomy (Q1: Ontology WG, All Mouse, All test-bed)• More Mouse Strains (Q1: All Mouse, Ontology WG)• Behavioral Paradigms (Q1: All Mouse, Ontology WG)

– Complete Cross-map of Key Anatomical Terms (Q2: Ontology WG, All Mouse)– Use for Term Mapping with Upload and Query (Ongoing, All)

Completed: – Major Mouse BIRN Strain Names (Ontology WG, UCSD, Drexel, UTHSC)– Initial set of Mouse Atlas Anatomical Terms (Ontology WG, UCSD, UCLA, Duke)– Used for Terms in MDA Atlas (UCLA, UCSD, Ontology WG)– Used for Terminology in BIRN Microarray Upload Interface (UCLA)

XCEDE:– Map Local Data to XCEDE for Data Sharing (Q2: All Mouse, CC)– Create Tools that Read and Generate XCEDE (Q2: All Mouse, CC)

Completed: – Comparison of Local Site Metadata Mapping into XCEDE (All Mouse)

MBAT/WOMBAT Goals

Release Version 1 of MBAT October 1:– Easy access to automatic upload Tools (Q2: All Mouse, CC)– Stable platform for Microarray data upload and discovery (Q1: UCLA,

UTHSC, CC) – Advanced query interface implemented (Q1: UCLA, All Mouse, CC)– Ability to display most Mouse BIRN data types within the context of an Atlas

(Q2: All Mouse, CC). Expand beyond Mouse Brain to:– Whole Mouse (Q4: Duke, Caltech)– Quail (Q4: Caltech)– Embryo (Q4: Caltech, UCLA)

– Easy access to Atlas-building Tools (Q3: UCLA, Drexel, Caltech)

Completed: – MBAT connection to upload Microarray Data for immediate query (UCLA)– Beta version of Microarray Infrastructure (UCLA, UTHSC, CC)– Components for Multiple Data Source Query (UCLA, CC, UCSD, UTHSC)– All Mouse BIRN data types currently viewable with MBAT (All Mouse)– First Implementations of Atlas Interoperability API and Server (UCSD, Drexel, UCLA)– ImageJ plug in for conversion of Amira to MBAT formats (Caltech)– Automatic and semi-automatic segmentation modules (Duke)– BrainGraph Editor for creation and editing of a Heirarchy (UCLA)

Mouse BIRN Publications in Past Year

Published Manuscripts and Book Chapters:Ali Sharief A, and Johnson GA, (2006) Enhanced T2 contrast for MR histology of the mouse brain. Magnetic Resonance in Medicine 56(4):717–725.Badea A, Nicholls PJ, Johnson GA, Wetsel WC (2007) Neuroanatomical phenotypes in the Reeler Mouse. Neuroimage 34(4):1363-74. Bug W, Gustafson C, Shahar A, Gefen S, Fan Y, Bertrand L, Nissanov J (2007) Brain spatial normalization: indexing neuroanatomical databases In: Neuroinformatics

(Crasto CJ, ed). Humana Press.MacKenzie-Graham A, Boline J, Toga AW (2007) Brain Atlases and Neuroanatomic Imaging In: Neuroinformatics (Crasto CJ, ed). Humana Press Mackenzie-Graham A, Tinsley MR, Shah KP, Aguilar C, Strickland LV, Boline J, Martin M, Morales L, Shattuck DW, Jacobs RE, Voskuhl RR, Toga AW (2006) Cerebellar

cortical atrophy in experimental autoimmune encephalomyelitis. Neuroimage 32(3):1016-23.Price DL, Chow SK, MacLean NAB, Hakozaki H, Peltier S, Martone ME, Ellisman MH (2006) High-Resolution Large-Scale Mosaic Imaging using Multiphoton Microscopy to

Characterize Transgenic Mouse Models of Human Neurological Disorders. Neuroinformatics 4(1):65-80.

In Press:Badea A, Ali Sharief A, Dale AM, Johnson GA, (Submitted) Computational anatomy in the C57BL/6J mouse brain. NeuroimageBraude I, Marker J, Museth K, Nissanov J, Breen D (In Press) Contour-based surface reconstruction using MPU impliCaltech models. Graph ModelsChin MH, Geng A, Khan A, Qian W, Petyuk VA, Boline J, Levy S, Toga AW, Smith RD, Leahy RM, Smith DJ, (Submitted) A genome-scale map of expression for a mouse

brain section obtained using voxelation. Physiological GenomicsGefen S, Kiryati N, Nissanov J (In Press) Level-set-based image to surface alignment. IEEE Trans Image ProcessGustafson C, Bug W, Nissanov J (In Press) NeuroTerrain-a client-server system for browsing 3D biomedical image data sets. BMC BioinformaticsMartone ME, Sargis J, Tran J, Wong WW, Jiles H, Mangir C (In Press) Database Resources for Cellular Electron Microscopy, In R. McIntosh (ed) Cellular Electron

Microscopy, Methods in Cell Biology, Volume 79Ruttenberg A, Clark T, Bug W, Samwald M, Bodenreider O, Chen H, Doherty D, Forsberg K, Gao Y, Kashyap V, Kinoshita J, Luciano J, Marshall MS, Ogbuji C, Rees J,

Stephens S, Wong G, Wu E, Zaccagnini D, Hongsermeier T, Neumann E, Herman I, Cheung k (In Press) Advancing Translational Research with the Semantic Web, BMC Bioinformatics

Abstracts:Boline JK, MacKenzie-Graham A, Shattuck D, Yuan H, Anderson S, Sforza DM, Wang J, Williams RW, Wong W, Martone ME, Zaslavsky I, Toga AW (2006) A Digital Atlas

and Neuroinformatics Framework for Query and Display of Disparate Data. Society for Neuroscience, Abstract #100.12Bug WJ, Gupta A, Gustafson C, Martone ME, Nissanov J, Wong WW, Zaslavsky I (2006) Integrating Brain Atlas Tools for Broad-field Morphometric Analysis and Semantic

Data Integration. Society for Neuroscience, Abstract #490.10Gupta A, Bean C, Bug W, Fennema-Notestine C, Martone ME, Turner JA, Grethe JS (2006) Creating a Community-Based Knowledge Management Framework for

Integrating Neuroscience Data Via Ontologies. Society for Neuroscience, Abstract #100.7MacKenzie-Graham A, Tiwari-Woodruff S, Strickland LV, Aguilar C, Peterson RS, Fubara B, Johnson GA, Toga AW, Voskuhl RR (2006) The neuropathology underlying gray

matter atrophy in autoimmune demyelinating disease. Society for Neuroscience, Abstract #474.4Price DL, Rockenstein E, MacLean NAB, Phung V, Masliah E, Ellisman MH (2006) Altered dopamine receptor immunoreactivity in CNS of transgenic mice overexpressing

alpha-synuclein. ICAD, Abstract, Madrid, Spain July 16Price DL, Rockenstein E, Phung V, MacLean NAB, Masliah E, Ellisman MH (2006) A Parkinsonian mouse model overexpressing alpha-synuclein: assessment of changes in

behavior and glutamate and dopamine receptor immunoreactivity. Soc. Neuroscience, Abstract #75.20.Riklin-Raviv T, Sachen N, Kiryati N, Ben-Zadak N, Gefen S, Bertrand L, Nissanov J (Submitted) Propagating distributions for segmentation of brain atlas. 2007 IEEE

International Symposium on Biomedical Imaging: From Nano to MacroSforza DM, Hartenstein P, Lacan G, Melega WP, Toga AW (2006) Mapping of multiple brain region gene expression in a mouse MPTP model of Parkinson’s disease.

Society for Neuroscience, Abstract #755.1Turner JA, Fennema-Notestine C, Martone ME, Laird AR, Grethe JS, Bug W, Gupta A, Bean C (2006) You say potato, I say potahto: ontological engineering applied within

the Biomedial Informatics Research Network. Society for Neuroscience, Abstract #100.6

Mouse BIRN and the Scientific Community

External groups have shown a great deal of interest in collaborating with us this past year including:

• International Neuroinformatics Coordinating Facility (INCF), Stockholm Sweden

– Digital Rodent Atlases and Neuroinformatics

• Richard Baldock and EMAP/EMAGE, Edinburgh University– Atlasing: embryonic gene expression

• Gully Burns and NeuARt II, Information Sciences Institute – Atlasing: connections and literature

• W3C Semantic Web Health Care/Life Science Interest Group, Massachusetts Institute of Technology

– Visualization system for Alzheimer’s and Parkinson’s

• ICS-MCI (Institut Clinique de la Souris and Mouse Clinical Institute), Strasbourg, France

– Visualization system for Gene Expression Profiling and Mapping

Location of Mouse BIRN Resource Users

Abbott Hospital of Tokyo U Roswell Park Cancer Ins U of MelbourneAcademia Sinica, Taiwan Howard Floray Ins SAIC U of MinnesotaAlex&er Fleming, BSRC Indiana U Sapporo Med U U of MunichAlpha-Gamma Technologies, Inc INMED Shiga U of Med Science U of North Carolina, Chapel HillAlzheimer Res Forum IGBMC, Strasbourg France Sintesi, Italy U of OsloArizona State U Ins of Arctic Bio, UA Fairbanks Smoky Hill High School U of PennsylvaniaBaylor College of Medicine Ins of Human Genetics, Newcastle Southern Methodist U U of PittsburghBeth Israel Deaconess Med Cnt Ins of Physics St. Boniface GHRC, Manitoba U of QueenslandBIRN-CC Jackson Laboratory SYColeman, L3 Communications U of Southern CaliforniaCairo U Johns Hopkins U Harvard-MIT Div of HS & Tech U of SurreyCardiff U Karolinska Inst J David Gladstone IND U of Tennessee, HSCCatholic U of Louvain Ludwig-Maximilians U, Munich Tsinghua U U of TexasCEA, France Massachusetts General Hospital Tulane U U of Texas, AustinCIMAT A.C., Mexico MIT Turku Centre for BioTech U of Texas, Houston MSChemical Abstracts Services Medtech U Autonoma de Madrid U of Texas, Med BranchCornell College NASA U de São Paulo U of Texas, SouthwesternDaedalus Informatics, Greece Nathan S. Kline Ins U Federal do ParÃ, Brasil U of WashingtonDePaul U Nat Ins of Neurology & Neurosurg U Hospital Basel, Switzerl& U of Wisconsin MilwaukeeDuke Cnt for In Vivo Microscopy Nat Nsc Ins of Singapore U of Alaska Fairbanks Utah State UDystonia Foundation Nevada Cancer Ins U of Bonn V&erbilt UEindhoven U, Netherl&s NIH/NINDS U of California, Los Angeles Wake Forest UEmory U NIRS, Japan U of California, San Diego Wayne State UGeorgetown U Oklahoma Med Res Foundation U of Colorado HSC Weill Cornell Med College

Georgia Ins of Tech Old Dominion U U of EdinburghWomen’s & Children’s Hosp, Adelaide

GlaxoSmithKline Philips Res, NATLAB U of Freiburg YaleHamilton College Portl& Community College U of Heidelberg ZheJiang U ChinaHCNR-CBI, Harvard Med School Purdue U U of LiverpoolHeidelberg Med School Res Cnt, Juelich U of Louis Pasteur, France