View
237
Download
0
Category
Preview:
Citation preview
Hoeck – Data Visualizations in the context of a datawarehouse 1
Data VisualizationsA guide to understanding the broader impact of small molecule candidates in the context of a datawarehouse
Data VisualizationsA guide to understanding the broader impact of small molecule candidates in the context of a datawarehouse
Wolfgang G. Hoeck, Ph.D.Amgen Inc. – Dept. of Research Informatics
Wolfgang G. Hoeck, Ph.D.Amgen Inc. – Dept. of Research Informatics
Hoeck – Data Visualizations in the context of a datawarehouse 2
Outline of this presentationOutline of this presentation
• Spotfire architecture overview and user communities
• Spotfire integration with Assay Datawarehouse
• What can be accomplished using this integration
• Approaches to consider for the future
• Spotfire architecture overview and user communities
• Spotfire integration with Assay Datawarehouse
• What can be accomplished using this integration
• Approaches to consider for the future
Hoeck – Data Visualizations in the context of a datawarehouse 3
Spotfire DecisionSite ArchitectureSpotfire DecisionSite Architecture
Hoeck – Data Visualizations in the context of a datawarehouse 4
Amgen’s Spotfire User CommunityAmgen’s Spotfire User Community
Hoeck – Data Visualizations in the context of a datawarehouse 5
Spotfire integration with AssayDatawarehouseSpotfire integration with AssayDatawarehouse
Hoeck – Data Visualizations in the context of a datawarehouse 6
Simplified Assay Data FlowSimplified Assay Data Flow
AssayDataStore
ActivityBase
AIMAssay
Datawarehouse
Low-ThroughputAssay Results
High-ThroughputAssay Results
Data In Data Out
• Unique identification for an assay and its results
• Standardized format for assay context (attribute/value pairs)
• Standardized format for assay results (Result types, Units)
• A place to check (QC) the results
• One place for “published” results
• Unique identification for an assay and its results
• Standardized format for assay context (attribute/value pairs)
• Standardized format for assay results (Result types, Units)
• A place to check (QC) the results
• One place for “published” results
Hoeck – Data Visualizations in the context of a datawarehouse 7
Extensive set of Information LinksExtensive set of Information Links
• One molecule – all assays
• Many molecules – all assays (with
or w/o pivoting)
• One assay – all molecules
• Many assays – all molecules (with
or w/o pivoting)
• One molecule – specific list of
assays
• Many molecules – specific list of
assays (with or w/o pivoting)
• Many more ………………..
• One molecule – all assays
• Many molecules – all assays (with
or w/o pivoting)
• One assay – all molecules
• Many assays – all molecules (with
or w/o pivoting)
• One molecule – specific list of
assays
• Many molecules – specific list of
assays (with or w/o pivoting)
• Many more ………………..
Challenges:- Achieving an acceptable performance- Understanding the path Spotfire chooses- Working with DBA’s- Creating Views- Documenting the Links- Managing Change
Hoeck – Data Visualizations in the context of a datawarehouse 8
A collection of Process GuidesA collection of Process Guides
Step 1:
Step 2:
Step 3:
Retrieve Vendor Data
Hoeck – Data Visualizations in the context of a datawarehouse 9
What can be accomplished using this integrationWhat can be accomplished using this integration
Hoeck – Data Visualizations in the context of a datawarehouse 10
Problem statement(s)Problem statement(s)• I have one or a set of candidates that I am
interested to further pursue. Before starting on any new experiments, can I see what others have done with these molecules? Gain a historical perspective?
• Can we identify patterns of biological behavior that is driven by chemical similarity?
• Can we identify patterns of biological behavior that is NOT driven by chemical similarity?
• Did we screen these compounds against target x?
• I am interested in target x, what are the best compounds we have in our library?
• ….
• I have one or a set of candidates that I am interested to further pursue. Before starting on any new experiments, can I see what others have done with these molecules? Gain a historical perspective?
• Can we identify patterns of biological behavior that is driven by chemical similarity?
• Can we identify patterns of biological behavior that is NOT driven by chemical similarity?
• Did we screen these compounds against target x?
• I am interested in target x, what are the best compounds we have in our library?
• ….
Hoeck – Data Visualizations in the context of a datawarehouse 11
One Molecule – Many AssaysOne Molecule – Many Assays
Search – Filter – Sort – Annotate - Filter
1.) Search ResultsByRoot Information Link
3.) Sort
2.) InteractiveFilter
Hoeck – Data Visualizations in the context of a datawarehouse 12
One Molecule – Many AssaysOne Molecule – Many Assays
Search – Filter – Sort – Annotate - Filter
4.) Annotate
5.) Filter
Hoeck – Data Visualizations in the context of a datawarehouse 13
Many molecules - Many Assays Looking for patterns …Many molecules - Many Assays Looking for patterns …
Similar pattern – Similar StructureSimilar pattern – Dis-similar Structures
Hoeck – Data Visualizations in the context of a datawarehouse 14
Tools & DataTools & Data
• Spotfire DecisionSite: Broad access to assay data – one molecule, all assays or many molecules, all assays
• AIM Datawarehouse: Published (verified) assay results from high-, medium and low-throughput assays
• ADAPT: Compound clustering by similarity• Excel: Manually curated assay context
(Annotations)• Assay Intelligence: Search and display
assay context (Annotations)
• Spotfire DecisionSite: Broad access to assay data – one molecule, all assays or many molecules, all assays
• AIM Datawarehouse: Published (verified) assay results from high-, medium and low-throughput assays
• ADAPT: Compound clustering by similarity• Excel: Manually curated assay context
(Annotations)• Assay Intelligence: Search and display
assay context (Annotations)
Hoeck – Data Visualizations in the context of a datawarehouse 15
Tools & Data – Data formatsTools & Data – Data formats
Compounds Assays
Assays
Com
pounds
• What you CAN GET:
– Sorting and filtering by assay annotations: Target, Function, Inducer, Readout, etc.
– Grouping by Compound Similarity and Assay Characteristics; SAR-patterns easier visible
• What you CANNOT GET:
– Structure display
• What you CAN GET:
– Structure display
– Filtering by structural classes
– Manual grouping by assay classes
• What you CANNOT GET:
– Sorting and filtering by assay annotations
Hoeck – Data Visualizations in the context of a datawarehouse 16
AnnotationsAnnotations
• Structure Class annotation• Target Class annotation• Inducer annotation• Cell Type annotation• ….
• Structure Class annotation• Target Class annotation• Inducer annotation• Cell Type annotation• ….
“Clean annotations are the key to enabling sorting and filtering operations to focus on areas of interest and eliminate unwanted noise that distracts from the important areas.”
Hoeck – Data Visualizations in the context of a datawarehouse 17
Case StudiesCase Studies
• Target x enzyme inhibitors 1.5 years into screen
• Target Y screen 6 months into screen
• Target x enzyme inhibitors 1.5 years into screen
• Target Y screen 6 months into screen
Hoeck – Data Visualizations in the context of a datawarehouse 18
Target x enzyme inhibitors <40nMTarget x enzyme inhibitors <40nM
1000+ compounds tested in 219 POC assays, 91300 results
Target Z
ModelCell-basedScreen
Promiscuous Tyr Kinase
Hoeck – Data Visualizations in the context of a datawarehouse 19
Target x enzyme inhibitorsTarget x enzyme inhibitors
Tyr Kinases
S/T KinasesGleevec and related structures
Hoeck – Data Visualizations in the context of a datawarehouse 20
Target Y Screen – Top 1000 IC50 HitsTarget Y Screen – Top 1000 IC50 Hits
Target Y
Hoeck – Data Visualizations in the context of a datawarehouse 21
Target Y Hit Cluster #93Target Y Hit Cluster #93
Target Y
T2
S23T15
Target Y hits of similar structure sorted ascending by selectivity towards target 2.
Target YCounter-target Selectivity
XVX Class of compounds
Hoeck – Data Visualizations in the context of a datawarehouse 22
Take Home MessageTake Home Message
• What you CAN DO:– Data Visualizations help you survey a larger
number of molecules over a larger number of assays
– Take broader look at your molecules behavior
– Look for patterns that stand out– Encourage others to submit their data
• What you CANNOT DO:– Make one click and get an answer– Take what you see as “Black and White”
• What you CAN DO:– Data Visualizations help you survey a larger
number of molecules over a larger number of assays
– Take broader look at your molecules behavior
– Look for patterns that stand out– Encourage others to submit their data
• What you CANNOT DO:– Make one click and get an answer– Take what you see as “Black and White”
Hoeck – Data Visualizations in the context of a datawarehouse 23
Approaches to consider for the futureApproaches to consider for the future
Hoeck – Data Visualizations in the context of a datawarehouse 24
The “3D spreadsheet”The “3D spreadsheet”
Root | AA1223 | AA2234 | AA3445 | AA2312 | AA3411 | AA1244 | Class
cell bioch cell bioch cell cell
T1 T1 T12 T22 T15 T32
Kinase Kinase Kinase Kinase Kinase Kinase
S/T S/T Tyr Tyr S/T S/T
wt wt wt Kin-d wt wt
1232343334545552331
577
3562666777458221
2
0.01000.01200.00541.2237
102.44560.11231.99872.34661.25510.00010.00120.92200.0453
IC50 POC IC50 POC IC50 IC50
Sort to rearrange
Filter to rearrange
11122333334555
Hoeck – Data Visualizations in the context of a datawarehouse 25
Data Integration for Analytical ProcessingData Integration for Analytical Processing
Hoeck – Data Visualizations in the context of a datawarehouse 26
The future - Connecting with pathways or interaction networksThe future - Connecting with pathways or interaction networks
Hoeck – Data Visualizations in the context of a datawarehouse 27
AcknowledgementsAcknowledgements
• Cell-based screen teams
Inflammation• Larry Proctor
• Dave Wolcott
• Simon Chatwin
• Jen Sonnenberg
• Michael Billesbach
• Keith Hoyle
• Ariela Hui
• Bruce Holmen
• Kailash Swarna
• Dave Balaban
RI• Tyrosine Kinase
Screen Team
CRC
What’s Next?
• Computational Chemistry team
MS• Target Screen TeamsHTS
Recommended