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Exploring and Understanding Adverse Drug Reactions by Integrative Mining of Clinical Records and Biomedical Knowledge http://euadr-project.org

PEDRO LOPES pedrolopes@ua.pt University of Manchester October 19th, 2010


EU-ADR

WORKFLOWS

Introduction Goals Challenges

Why? Taverna UX

WEB PLATFORM

Architecture Taverna Open Issues


EU-ADR

WORKFLOWS

Introduction Goals Challenges

Why? Taverna UX

WEB PLATFORM

Architecture Taverna Open Issues


BACKGROUND ‣ DRUG • “A pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.” Wikipedia

‣ ADVERSE DRUG REACTION • “An adverse drug reaction (abbreviated ADR) is an expression that describes harm associated with the use of given medications at a normal dose. The meaning of this expression differs from the meaning of "side effect", as this last expression might also imply that the effects can be beneficial. The study of ADRs is the concern of the field known as pharmacovigilance.” Wikipedia


BACKGROUND ‣ DRUG • “A pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.” Wikipedia

‣ ADVERSE DRUG REACTION • “An adverse drug reaction (abbreviated ADR) is an expression that describes harm associated with the use of given medications at a normal dose. The meaning of this expression differs from the meaning of "side effect", as this last expression might also imply that the effects can be beneficial. The study of ADRs is the concern of the field known as pharmacovigilance.” Wikipedia

DRUG + ADR = SIGNAL M01AH02 (Rofecoxib) + UGIB (Upper Gastro-Intestinal Bleeding)


LAUNCHING A NEW DRUG ‣ BEFORE THE MARKET • Test with thousands of subjects • Some Adverse Drug Reactions are not detected

‣ IN THE MARKET • Clinicians must recognize and report suspected harmful “side effects”

‣ SPONTANEOUS REPORTING SYSTEMS • Main pillar to detect signals in pharmacovigillance


LAUNCHING A NEW DRUG ‣ BEFORE THE MARKET • Test with thousands of subjects • Some Adverse Drug Reactions are not detected

‣ IN THE MARKET • Clinicians must recognize and report suspected harmful “side effects”

‣ SPONTANEOUS REPORTING SYSTEMS • Main pillar to detect signals in pharmacovigillance

There is an entire ecosystem associated with pharmacovigillance

!


GOAL

The overall objective of the EU-ADR project is the design, development and validation of a computerized system that exploits data from electronic healthcare records and biomedical databases for the early detection of adverse drug reactions.


GOAL

The overall objective of the EU-ADR project is the design, development and validation of a computerized system that exploits data from electronic healthcare records and biomedical databases for the early detection of adverse drug reactions.

â˜ş

Some kind of intelligent application that finds ADRs in literature, patient data and other databases.


CHALLENGES ‣ HOW TO BUILD THIS?

Application: (Search + Collect) x (Literature + Patient Data + Biomedical Databases) x User Interactions


CHALLENGES ‣ HOW TO BUILD THIS?

Application: (Search + Collect) x (Literature + Patient Data + Biomedical Databases) x User Interactions


CHALLENGES ‣ HOW TO BUILD THIS?

Application: (Search + Collect) x (Literature + Patient Data + Biomedical Databases) x User Interactions


EU-ADR

WORKFLOWS

Introduction Goals Challenges

Why? Taverna UX

WEB PLATFORM

Architecture Taverna Open Issues


EU-ADR

WORKFLOWS

Introduction Goals Challenges

Why? Taverna UX

WEB PLATFORM

Architecture Taverna Open Issues


EHR 1

EHR 2

WORKFLOW

EHR n Text Mining Terminology Mapping

Data Extraction Data Mining

Signal Detection Ranked signal list

Signal Substantiation Re-ranked signal list

Retrospective and Prospective System Validation

Literature Known Side Effects Pathway Analysis In silico simulation


HOW? ‣ DATABASES • Public ‣ UniProt, DailyMed, DrugBank, PharmGKB, NCBI * ... • Partner-specific ‣ Huge datasets

‣ WEB SERVICES • Public web services • Partner-specific


HOW? ‣ DATABASES • Public ‣ UniProt, DailyMed, DrugBank, PharmGKB, NCBI * ... • Partner-specific ‣ Huge datasets

‣ WEB SERVICES • Public web services • Partner-specific

How to connect everything in a single system?

?


HOW? ‣ DATABASES • Public ‣ UniProt, DailyMed, DrugBank, PharmGKB, NCBI * ... • Partner-specific ‣ Huge datasets

‣ WEB SERVICES • Public web services • Partner-specific

How to connect everything in a single system?

?


REQUIREMENTS ‣ DATA PRIVACY • Sensitive, unpublished, data • There’s money attached (pharmaceutical companies)

‣ USERS • From clinicians to programmers • Single lab scale (local data) vs Project scale (web environment)

‣ PERFORMANCE • Huge datasets ‣ Thousands of signals


SECURITY


SECURITY ‣ TESTED • Single Sign On

‣ SOLUTION • WSO2 Platform

• OpenID

‣ Custom Identity Provider

• Shibboleth

‣ Secure web services

• OAuth

‣ Straightforward to install

• OpenASelect • HTTPS, WSDL-S


SECURITY ‣ TESTED

‣ SOLUTION

• Single Sign On

• WSO2 Platform

• OpenID

‣ Custom Identity Provider

• Shibboleth

‣ Secure web services

• OAuth

‣ Straightforward to install

• OpenASelect • HTTPS, WSDL-S

THANK YOU!


UX


UX ‣ LOCAL • Local workflow execution • Local data analysis

‣ WEB • Remote workflow execution ‣ Process the entire pipeline online • Remote data analysis ‣ Analyze workflow results and provenance data


UX ‣ LOCAL • Local workflow execution • Local data analysis

‣ WEB • Remote workflow execution ‣ Process the entire pipeline online • Remote data analysis ‣ Analyze workflow results and provenance data

Web Platform = Taverna + Services + XSD

!


FIRST WORKFLOW


http://bioinformatics.ua.pt/euadr_test


EU-ADR

WORKFLOWS

Introduction Goals Challenges

Why? Taverna UX

WEB PLATFORM

Architecture Taverna Open Issues


EU-ADR

WORKFLOWS

Introduction Goals Challenges

Why? Taverna UX

WEB PLATFORM

Architecture Taverna Open Issues


WEB PLATFORM


WEB PLATFORM ‣ WEB SERVICES • Execute partner web services • View results

‣ WORKFLOWS • Workflow management • Search, browse and execute workflows • Analyze and compare results

‣ DATASETS • Process entire datasets ‣ All workflows x ~ 4000 signals per dataset • Analyze and compare final and intermediate results ‣ “Signal evolution”


PIPELINE


PIPELINE 1.UPLOAD DATASET • From users’ desktop to web platform (.xls)

2.READ DATASET • Web Platform reads file to database 3.PROCESS DATASET • Generate workflow XML inputs 4.EXECUTE WORKFLOWS • Launch threaded Taverna executions

5.STORE WORKFLOW RESULTS • Save full XML output 6.UPDATE DATASET • Update dataset information with output results

7.DISPLAY WORKFLOW RESULTS • Show results in web platform


ARCHITECTURE


Taverna Connect

CLI

ARCHITECTURE

security


TAVERNA CONNECT ‣ REQUIREMENTS • Organize datasets into multiple workflow execution ‣ Workflow accepts any number of signals in input • Output results as XML files ‣ One signal = One XML file • Load files into web platform ‣ Read XML

‣ CONDITIONS • Performance • Time • Efficiency • Size • Complexity


TAVERNA CONNECT ‣ REQUIREMENTS • Organize datasets into multiple workflow execution ‣ Workflow accepts any number of signals in input • Output results as XML files ‣ One signal = One XML file

‣ CONDITIONS • Performance • Time • Efficiency • Size • Complexity

• Load files into web platform ‣ Read XML

BEST SOLUTION? syscalls, web services, disk access, web access, pooling, transmission, network, hosts...


COMMAND LINE INTERFACE ‣ STRATEGY • Define (static) workflow input/output directories • Generate XML input • Execute Java syscall (threaded) • Read XML output

Straightforward

Static

Simple

Time

Streamlined

Efficiency

Handles large files

“It’s a syscall!”


COMMAND LINE INTERFACE ‣ STRATEGY • Define (static) workflow input/output directories • Generate XML input • Execute Java syscall (threaded) • Read XML output

Straightforward

Static

Simple

Time

Streamlined

Efficiency

Handles large files

“It’s a syscall!”

JAR package? Performance improvement? Full security? ...


TAVERNA SERVER ‣ STRATEGY • Develop Java client package (do you have it?) • Generate and transmit XML input • Execute workflow • Check for results • Download results

“It’s not a syscall!”

Complexity

Modular (dynamic) design

Efficiency Network Handles large files


TAVERNA SERVER ‣ STRATEGY • Develop Java client package (do you have it?) • Generate and transmit XML input • Execute workflow • Check for results • Download results

“It’s not a syscall!”

Complexity

Modular (dynamic) design

Efficiency Network Handles large files

Simplified? Lighter? Performance? Client packages?


CONCLUDING ‣ STATUS • Beta release soon

‣ NEXT • More data • More services • More workflows • More users


CONCLUDING ‣ STATUS

‣ NEXT

• Beta release soon

• More data • More services • More workflows • More users

What’s next for Taverna? (What’s in it for us?)

What is the best path?


TAVERNA IS GREAT!


http://bioinformatics.ua.pt


http://bioinformatics.ua.pt ‣ MIND | Microarray INformation Database • http://bioinformatics.ua.pt/mind

| Rare Disease Portal • http://bioinformatics.ua.pt/diseasecard

‣ QuExT | Literature Query Expansion Tool • http://bioinformatics.ua.pt/quext

| Web Analysis of the Variome • http://bioinformatics.ua.pt/WAVe

‣ GeneBrowser2 • http://bioinformatics.ua.pt/genebrowser2


ME pedrolopes@ua.pt

http://pedrolopes.net

/pedrolopes

/pdrlps


THANK YOU!


Taverna & EU-ADR  

Presentation shown to Taverna development team to kick-off the discussion on how to improve and enhance Taverna usage in the EU-ADR Web Plat...

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