WU ADRCDATA INTEGRATION AND SHARING:

PLAN & PROGRESS

http://nagarajanlab.wustl.edu

*Dr. Nagarajan is on the Scientific Advisory Board of Persistent Systems. Persistent Systems does not fund Dr. Nagarajan’s research.

Study Participant

Peripheral LeukocytesSerum / PlasmaFrozen Tumor BiopsyBone MarrowFFPE Block

RxPeripheral LeukocytesSerum / PlasmaFrozen Tumor BiopsyBone MarrowFFPE Block

Biospecimen Bank and

Informatics

Mutation Profiling

Proteomics

Gene Expression Microarray

FFPE qRT-PCR

Biomarker Validation

aCGH DB

DB

DB

DB

Clinical Data Molecular Data

IHC / Cell Assays

Integrative Analysis

Translational Research Paradigm

• Clinical Core– Patient demographic information, family history, health history, depression inventories,

physical examination, standard cognitive tests , and CDR

• Biomarkers Core– Fasting plasma and cerebrospinal fluid- Levels of total protein, hemoglobin A1C,

homocysteine, folate, Aβ, tau, apoE, and other biomarkers

• Genetics Core– Non-fasting blood, plasma, serum, buffy coat, and DNA during the initial visit and every 3

years thereafter for genotyping APOE and other genetic risk factors

• Neuropathology Core– Post-mortem frozen and fixed brain tissue- Quantitation of senile plaques, neurofibrillary

tangles, neuron counts, amyloid angiopathy, Lewy bodies, and vascular pathology

• Psychometric Core– Primary, working, episodic, and semantic memory, abstract reasoning,

visuospatial/visuoconstructive dysfunction, psychomotor deficits

• Neuroimaging Core– MRI (3D T1- and T2-weighted scans, diffusion-weighted scans, echo-planar imaging scans);

Amyloid PET scan data and derived images

WU Alzheimer’s Disease Research Center Cores

Core Participants Encounters BiospecimensClinical 3,489 11,486 N/APsychometric 3,036 9,554 N/ANeuroimaging 716 1,346 N/ANeuropathology 1,255 1,255 ~62,000Genetics 3,669 5,467 ~170,000Biomarkers 465 497 ~25,000

WU ADRC Data Integration Problem

BiomarkersCore

ClinicalCore

PsychometricCore

NeuroimagingCore

NeuropathologyCore

GeneticsCore

SAS

Excel

Filemaker Pro

MySQL

PostgreSQL ?

Translational Research Paradigm

Study Participant

Peripheral LeukocytesSerum / PlasmaFrozen Tumor BiopsyBone MarrowFFPE Block

RxPeripheral LeukocytesSerum / PlasmaFrozen Tumor BiopsyBone MarrowFFPE Block

Biospecimen Bank and

Informatics

Mutation Profiling

Proteomics

Gene Expression Microarray

FFPE qRT-PCR

Biomarker Validation

aCGH DB

DB

DB

DB

Clinical Data Molecular Data

IHC / Cell Assays

Integrative Analysis

Collection Site Specimen Bank Investigator Lab

Biospecimen Inventory

Collect Ship

Process Store

Distribute

Studies Database

Add ProtocolAdd Annotation

Accession SpecimenCreate SpecimenDistribute

SearchOrder

Workflow of a Translational Research Study

Intake Site

Register Participant

Register Participant

Add Collection Event

Exam Site #1 Exam Site #2 Exam Site #n…

Add Exam Site Details at Encounter Event

Collection Site Specimen Bank Investigator Lab

Biospecimen Inventory

Collect Ship

Process Store

Distribute

Studies Database

Add ProtocolAdd Annotation

Accession SpecimenCreate SpecimenDistribute

SearchOrder

Workflow of the WU ADRC

Intake Site

Register Participant

Register Participant

Add Collection Event

Exam Site #1 Exam Site #2 Exam Site #n…

Add Exam Site Details at Encounter EventClinicalCore

ClinicalCore

PsychometricCore

NeuroimagingCore

Biomarkers, Genetics, &

NeuropathologyCores

ClinicalCore

Collection Site Specimen Bank Investigator Lab

Biospecimen Inventory

Collect Ship

Process Store

Distribute

Studies Database

Add ProtocolAdd Annotation

Accession SpecimenCreate SpecimenDistribute

SearchOrder

Clinical Studies Data Management

Intake Site

Register Participant

Register Participant

Add Collection Event

Exam Site #1 Exam Site #2 Exam Site #n…

Add Exam Site Details at Encounter EventClinicalCore

ClinicalCore

PsychometricCore

ClinicalCore

Studies Database

ClinPortal: Representing & Storing Clinical Studies

• Robust and scalable clinical studies management system

• End user graphical design of clinical case reports

• Automatic generation of forms for data entry

• Graphical interface to query and download study data

PARTICIPANTAn individual who has consented to a study

1

many

PARTICIPANT STUDY REGISTRATIONAn event in which a

PARTICIPANT is registered to a CLINICAL

STUDY

CLINICAL STUDYA set of attributes that dictates how a study is

to be conducted

many

1

ENCOUNTER EVENTAn encounter with a

PARTICIPANT enrolled on a CLINICAL STUDY at a

point in time when data is captured

1

many

ANNOTATIONOne or more data

elements describing the PARTICIPANT

1 many

1 many

ClinPortal Concepts

ClinPortal Study Definition

• Define clinical study encounter events

• Define data elements (attributes or variables) to capture at each encounter event

• Model data elements as appropriate to the biomedical domain (e.g. group biomarkers together and organize physical exam findings per anatomic location)

• Create forms containing variables

• Associate form(s) to one or more encounter events

Encounter events and annotations

Participant demographics page

ClinPortal: Participant Registration

Encounter events and annotations

Data entry form(s)

ClinPortal: Encounter Event and Data Entry

Collection Site Specimen Bank Investigator Lab

Biospecimen Inventory

Collect Ship

Process Store

Distribute

Studies Database

Add ProtocolAdd Annotation

Accession SpecimenCreate SpecimenDistribute

SearchOrder

Workflow of the WU ADRC

Intake Site

Register Participant

Register Participant

Add Collection Event

Exam Site #1 Exam Site #2 Exam Site #n…

Add Exam Site Details at Encounter Event

Biomarkers, Genetics, &

NeuropathologyCores

Biospecimen Inventory

• Comprehensive biospecimen informatics system– Tissue bank functions

• Protocol Management• Inventory Tracking• Quality Assurance / Quality Control Parameters

– Annotation Features• Concept-coded surgical pathology reports• Discrete Clinical and Pathology Attributes

– Researcher functions• Graphical query interface• Biospecimen ordering system

Tissue Suite

Tissue Suite Concepts

PARTICIPANTAn individual from

whom biospecimens are collected

1

many

PARTICIPANT PROTOCOL

REGISTRATIONAn event in which a

PARTICIPANT is registered to a

COLLECTION PROTOCOL

COLLECTION PROTOCOL

A set of attributes that dictates how

biospecimens are to be collected

many1

SPECIMEN COLLECTION GROUPOne or more specimens collected at one point in

time from a PARTICIPANT enrolled on a

COLLECTION PROTOCOL

1

many

SPECIMENA tissue or fluid collected from a PARTICIPANT

1 many

DISTRIBUTION PROTOCOL

A set of attributes that dictates how

biospecimens are to be used for a correlative

science study

many1

1 many

Aliquot Derivative

Participant demographics page

CP registration page

Tissue Suite: Participant Registration

Creation of all expected specimens, derivatives, and aliquots based on CP definition

Calendar clock offset

Collection event (SCG) status

Tissue Suite: Add Specimen Collection Group

Label printing 1. Indicate expected specimens collected

2. Indicate expected derivatives / aliquots created

3. Pre-defined / editable labels, quantities, and storage destination

Tissue Suite: Add Specimen Collection Group

De-Identified Report Information

Category Highlighter

PROCEDURE ORGAN DIAGNOSIS Modifier [Report de-identified (Safe-harbor compliant) by De-ID v.6.14] [Final Diagnosis] Consult from CHLA, Los Angeles, CA: ***PATH-NUMBER[1] (**DATE[Nov 28 05])): Left parotid gland, resection: MUCOEPIDERMOID CARCINOMA, LOW GRADE (SEE NOTE). [Microscopic Description] Parotid gland contains a multilocular cystic lesion. Some of the smallercysts are filled with mucoid debris. The cystic lesion is embedded in a dense, collagenous pseudo-capsular reaction with entrapped smaller cysts within the dense collagen. There is extensive inflammation around the smaller peripheral cysts, and in places there is follicular lymphoid tissue around the larger cystic areas. The lining varies. Most of the larger cysts are lined by a mucoid layer rich in goblet cells that are very large and often ballooned with concretions. There are cuboidal and squamous areas admixed with oncocytic foci. In some areas, the lining is proliferative, and there are multiple layers that appear disorganized. The collagenous reaction that encompasses squamoid hyalines approaches within one high-power field of the inked margin of resection. The surrounding gland is locally atrophic, with a chronic periductal inflammatory component.

Tissue Suite: Other Features

Progress to Date

• Neuropathology Core migrated to Tissue Suite for prospective biospecimen collection; Creating forms for pathology annotation and NACC Neuropathology

• Genetics Core being migrated to Tissue Suite

• Clinical and Psychometric Core data elements being modeled

• Plan to engage Biomarkers Core in January 2009

• Neuroimaging Core integration by late 2009

Institution to Global IntegrationcaBIG: cancer Biomedical Informatics Grid

CTSA: Clinical and Translational Science Award

Summary: ADRC Data Integration and Sharing

TissueSuite ClinPortal XNAT

BiomarkersGenetics

Neuropathology

ClinicalPsychometric

Neuroimaging

TissueTissueSuiteSuite

ClinPortalClinPortal

caGrid BIRN

GRID

AcknowledgmentsOn-site TeamSunita KoulJoanne ZhaoGeorge JosephRekha MeyerYongkee ChoLi-Wei ChangHrishikesh DeshmukhMukesh SharmaBurr FontaineCaerie HouchinsDan FlasarJahangheer ShaikEdmond AbrahamianHaresh BhatiaDianne OliverAmmar HalawaDaniel FaresDavid MulvihillBijoy GeorgeRobnet Kerns

Software Engineers

Project ManagerSrikanth Adiga

Abhijit Naik Mandar Shahasrabudhe Sachin LaleAmit Bidkar Mandar Shidhore Sagar BaldwaAmit Doshi Milind Kulkarni Sakshi RaoAnup Agrawal Namita Hardikar Salil GavankarAshish Gupta Nitesh Marwaha Sanket AtreAtul Jawale Pawan Maheshwari Santhoshkumar ChintalaBaljeet Dhindhwal Pooja Arora Sarita SoniBhagyasree Chaudhuri Pooja Deshpande Seema GoswamiChandrakant Talele Poornima Gokhale Shailesh WaghChetan Patil Poornima Govindrao Shital LawhaleChitra Garg Pradhnya Unawane Siddharth ShahDeepak Shingan Prajakta Sakat Snehil GuptaDeepali Ahirao Prasanna Kashikar Srinath KrishnamurthyDeepti Shelar Prashant Bandal Sujay NarkarFalguni Sachde Prashant Kadam Sumit DeshmukhGanesh Naikwade Pratha Budhrani Sumit GauravHrishikesh Rajpathak Preeti Munot Sunil AgrawalJanhavi Hasabnis Rachana Dharpure Supriya DankhJasbir Sachdeva Rajesh Patil Swati ChavanJignesh Wala Rajesh Vyas Syed RizviJuberahamad Patel Rakhi Garg Taraben KhoiwalaKalpana Thakur Ravi Kumar Vaishali KhandelwalKiran Pinnamaneni Ravindra Jain Vijay PandeKunal Kamble Reena Athawle Vimal RawatLalit Chand Rinku Arora Vipin BansalLeena D'Almeida Rukhsana Sameer Virender MehtaMadhumita Shrikhande Rupali Ratnaparakhi Vishvesh MulayMadhurima Bhatacharjee Rushikesh Kanap Yogesh LeveMandar Deshmukh Rushikesh Subedar Yogesh Shetty

WU ADRCJohn MorrisADRC Core DirectorsADRC Personnel