Integrative workflows for
Bio Research &
Medical Research
Lim Teck Sin
CEO
Summary of Presentation
KOOPrime, an Introduction
Workflows for Bio Research
Microarray
Oligo Design
Sequencing
Disease Surveillance
Animal Management
Workflows for Medical Research
iTrials
Mission Statement
Leading Provider of
IT Products and Services
for the Life Sciences Industry in Asia
Outreach of KOOPrime
CAS
HP
BEIJING
Mitsui
Jetro
JAPAN
NNTP
NANNING
INDIA
HKUST
Nanshan
BIOTEC
SirirajH
HONGKONG
THAILAND
MPOB
MARDI
MALAYSIA
NUS
I2R
IMCB
SINGAPORE
Office/Staff
Singapore – the Little Sparrow
HIGH THROUGHPUT
SCREENING
GENOMICS,PROTEOMICS
LAB MGT AND ANALYSIS
KOOPORTAL
KOOPLATFORM
PRE-CLINICAL
EVALUATION SYSTEM
CLINICAL
TRIAL SYSTEM
FDA COMPLIANCE &
VALIDATION
REGISTRY
& HL7 EXHANGE
SYSTEM
Bio Research
Pharmaceutical
Medical Research
Industrial
HEALTH TRACKING
SYSTEM
KOOP-EDUCATION
SYSTEM
KOOPrime’s business spans across
organizations in Asia
KOOPrime’s business spans across organizations in Asia
BioResearch
BioResearch Vertical
User: National University Singapore
Sequence Discovery Platform
User: Malaysia Palm Oil Board
Oligo Discovery Platform
User: NovusGene, Japan
User: National Cancer Center
Microarray Discovery Platform
User: Bioprocessing Technology Center
User: Malaysia Agricultural R&D Institute
Animal Facility Platform
User: IMCB, Singapore
Management of Genotypic Info
iBioSuite
Cut down duplication and maximize
resources
Microarray Discovery Platform
Fabrication
Data Management
Genomic Data
Source
Barcode scanner
Clustering
Purification Unit
Proteomic Data
Source
Genome Mapper
Pathway
Data Visualization
 Significant rules often have low-ranked attributes
Gel Electrophoresis
If 32598_at <= 29 and 33886_at <= 10 and 34950_at <= 5,
Then this is a tumor cell (49/52). *
 This rule is significant with 94% (49/52) coverage
 Gene 33886_at and 34950_at are found to have low coverage and are
ranked 210th and 266th out of 12600 genes respectively
Total
K trees
 Alternative trees can perform equally well in prediction
32598_at
33886_at
<=10
34950_at
<=5
Tumor
Normal
>5
Normal
<=29
34950_at
>10
Microarray Printer
>29
<=-6
Tumor
32598_at
38406_at
>-6
Normal
<=420
Tree-2
Tree-k
 Two different/disjoint trees are generated with the same dataset*
<=29
Tree-1
Genome Mapper
>29
Normal
>420
Data Analytical Tool
37639_at
Tumor
<=127
Normal
>127
Tumor
 The rules contain low-ranked genes (e.g. 34365_at is ranked 1878 th)
Data Mining and Analysis
* Singh, D., Febbo l,P.G., Ross,K., Jackson,D.G., Manola,J., Ladd,C., Tamayo,P., Renshaw ,A.A., D’Amico,A.V., Richie,J.P. et al. (2002) Gene expression correlates of clinical
prostate cancer behavior. Cancer Cell, 1, 203-209.
User: National Cancer Center
Microarray Scanner
User: Bioprocessing Technology Institute
Pathway
Interaction
Microarray Discovery Platform
1st Generation – RMI based KOOPlatform (1999)
KOOPBox
Create/
Modify/
Execute
workflows
KOOPAgent
Communicate between
Different machines
KOOPServer
Monitor flows
Microarray Discovery Platform
1st Generation – Stitching of Bubbles
• Creation and deployment of bubbles
• Linking ( mapping IO ) bubbles based on Workflow requirements
Visual Stitching of
Objects (bubbles)
Microarray Discovery Platform
1st Generation – Integration Platform
Create
KOOP
Visualize results
(graphs, emails)
Print results
Collect
machine data
Broadcast
results
KOOPServer
Download
data
Monitor
flows
Compute
results
Microarray Discovery Platform
Microarray Fabrication Workflow (2001)
Vendor File Processing
PCR Plate Creation
Working Plate Creation
PCR Flagging
Growth Plate Creation
Pooling Plate Creation
Growth Flagging
Pooling
Plasmid Plate Creation
Array Printing
Array QC
Microarray Discovery Platform
Microarray Data Management & Analysis Workflows
Experiments
Technical Replicate
Cross Normalization
Samples
Biological Replicate
Cross Normalization
Hybridization
Normalization
Gene Filtering
Clustering
Microarray Discovery Platform
Flexibility in Workflow Design via KOOPBox
Microarray Discovery Platform
Preparation of Probe DNAs
• Probe
Selection from databases ( UniGene, GenBank etc )
• Replication of 96-well-plates of bacterial clone stocks
• Growth flagging of clones and restreaking of problem clones
Microarray Discovery Platform
Array Printing
• Spotting
of PCR products representing specific genes onto
glass slides.
• Layout 96 well plates
on 384 well plates
• Layout 384 well plates
on DNA microarrays
Microarray Discovery Platform
Simplification for Non-Power Users
• Maintain operator profiles based on role in a specific project
• Create templates (by linking bubbles) that mimic actual workflow
• Assign templates to operators
Administrator’s View
Operator’s View
Microarray Discovery Platform
2nd Generation Web based Workflows (2002)
• Go beyond Intranet
• KOOPlatform 4.0: Web protocols, in addition to RMI
• KOOPortal: Further simplification, accessibility to non-workflow features
Presentation
Layer
Business
Layer
Data Access
Layer
Session
Beans
Data
Access
Objects
Servlets
Internet
User
Handler
Database
JSP
File System
Analysis
Clients
Microarray Discovery Platform
Flexibility for Workflows
Microarray Discovery Platform
GLP for Microarray Fabrication Workflow
Oligo Discovery Platform
Mini-PC Grid (2003)
LivePortal
“KP's P2P technology was implemented for up-version of parallel computing
environment, which enabled heavy design calculation using internal PCs during
night. This system becomes NGI's business infrastructure because of its highly
cost effective performance due to almost full automated probe data base
accumulation."
Dr Seiichi Nemoto, General Manager, Bioinformatics Div., NovusGene Inc.
Sequence Discovery Platform
Ultra-Simplified Web based Workflows for 500+ Users (2004)
Sequence Discovery Platform
Portal to Share & Manage DNA Sequencing Resources
Sequence Discovery Platform
Mixed Portal-Workflow Environment (2006)
Wet Lab Sequencing
Routine analysis
Provide web based Services
Flexi analysis
Sequence Discovery Platform
Personalized Workflows: Phylogenetic Analysis
Sequence Discovery Platform
Workflows to save time: Proteomics Analysis
Showorf
Peptide Display
CHIPS / CUSP
Codon Computation
fuzzpro
Peptide Search
Digest
Cutting Positions
CheckTrans
ORF Output
Rapid Disease Outbreak Management System
To Facilitate Nation-Wide Responses to Emergencies (2005)
• Measures for Disease Surveillance and Disease Outbreak management
• End-to-end Integration with various Life Science ‘Lego Blocks’
• To facilitate rapid and controlled manufacturing of diagnostic kits, vaccines, etc.
• To partner key organizations (e.g. IDA, MOH, NGO) to develop Outbreak IT platform
Demonstration of system to
minister at Asia Grid 2005
Rapid Disease Outbreak Management
Integration with GoalNet, Taverna, Protege
Rapid Disease Outbreak Management
Mapping of Resources / Bottlenecks
Generate ArrayId
Sample Processing
Homology Search w GRIDBLAST
Generate Experiment
DNA Sample Plate Mapping
Seq Annotation w GenBank
Hybridize Array with Sample
DNA Sequencing
SendGeneListFile to ProbeDesign
Collect Microarray Results
Collect ABI data
ProbeDesign
Perform Single-array Normalization
Store ABI data
Send ProbeList to Oligo Synthesizer
Filter data
QualityCheck
Probe QC
Cross normalization
Vector Masking
Send CompletedProbeList to
Microarray Discovery System
Discovery & prediction with PCL/CS4
Map ProbeToPlates
Visualize with MGM or HCluster
Configure Microarray Printer
Generate Hits for Field test
Vector Trimming
Contigs Assembly
WetLab
Visuals/Programs
Rapid Disease Outbreak Management
Detailed Mapping for Microarray Workflows
Generate Experiment
previous
Generate ArrayId
Generate Experiment
Probe List Preparation
Hybridize Array with Sample
Clinical Sample Preparation
Microarray Data Mgt
Collect Microarray Results
Perform Single-array Normalization
Filter data
Cross normalization
Microarray Discovery Discovery & prediction with PCL/CS4
Primer Design
Microarray Visualization
Visualize with FPGA HCluster
Primer/Probe Selection/Re-Design
NYP
WetLab
Visual
FPGA/NTU
I2R / Taverna
Visualize with MGM
Hits Lits Generation
Diagnostic Kits
Manufacturing
Generate Hits for Field test
Scale up Manufacturing
Animal Management Platform
‘Hotel’ system to manage workflow for 13,000 Tanks of Fishes (2006)
Medical Research
Medical Research Vertical
Clinical Decision Support
Tissue Registry
HL7 Medical Data Exchange
Clinical Research Platform
User: National University Hospital, Singapore
User: Tan Tock Seng Hospital, Singapore
User: Ministry of Health, Singapore
User: National University Hospital, Singapore
Management of Phenotypic Information
Research databanks for research and delivery
iTrials
iTrials - Clinical Research Platform
End-to-End Integration of Clinical Research Workflows (2006)
Reports
Questionnaires
• Recruit Interviewers
• Collect Questionnaires
• Data Entry
• Blood Sample
Long Term Storage
Documents
Clinical Centre
• Blood Sample Tests
Forms
Samples
Samples
• Health Screening
• Blood Samples:
• Urine Sample Tests
iTrials - Clinical Research Platform
Systematic follow-up on health screening & clinical trials
iTrials - Clinical Research Platform
Understand the value and cost effectiveness of clinical protocols
iTrials - Clinical Research Platform
Standards for Medical Records Exchange
A Laboratory Message in HL7 format
Message Header Segment(MSH): Intent, source, destination, syntax of message
Patient Identification (PID): Patient identifying and demographic information
Observation Request (OBR): A request for diagnostic services/clinical observation
ZLR: Data of importance to public health, unique to lab message
OBX: A single observation of individual tests performed and results
Acknowledgement
We Don’t Work Alone
Hewlett Packard
• Bio Research sector development
• HKH Bioinformatics Centre
IBM
• Medical Research sector development
KOOPrime Consulting
• GXP Training
Microsoft
• Medical Research sector development
Nanyang Polytechnic
• Pathway Genome Mapper
Nanyang Technology University
• GoalNet
National University of Singapore
• Domain Expertise
• Disease Surveillance
Progeniq
• HPC Computing Setup
• FPGA
Looking for partners that
Specialize in Visual Components
Looking for partners to
Distribute iBioSuite & iTrials
We Welcome Collaboration
KOOPrime SINGAPORE
21 Science Park Road, #03-28 The Aquarius, Singapore Science Park II
Tel/Fax: 65-6775 4220/6775 4206
KOOPrime Consulting
21 Science Park Road, #03-28 The Aquarius, Singapore Science Park II
Tel/Fax: 65-6775 4220 X 103 /6775 4206
KOOPrime MALAYSIA
KOOPrime (M) Sdn. Bhd., 729, Block B, Mentari Business Park,
Jalan PJS 8/5, 46150 Petaling Jaya
KOOPrime HONG KONG
HKUST-KOOPrime-HP Bioinformatics Centre, Hong Kong University of Science and Technology,
Clearwater Bay, Kowloon, Hong Kong
Email: KOOP-HKH@kooprime.com
tecksin@kooprime.com
Thank You