spotfire · conclusions: spotfire™ in drug discovery • key advantages – visualization...

Spotfire™ Across the Drug Discovery Enterprise:

The Cytokinetics Case Study

Spotfire™ Across the Drug Discovery Enterprise:

The Cytokinetics Case Study

Vadim Kutsyy, Ph.D.Wesley Zink

October 2003

Cytokinetics: Company SnapshotCytokinetics: Company Snapshot

• Cell biology driven; focus on cytoskeleton

• Oncology drug in Ph I; initiating broad Ph II in Q4 2003

• Major cancer alliance with GlaxoSmithKline

• Emerging clinical pipeline; 2 IND’s in next 6-9 months

• Raised >$130 million; strong cash position

Cytokinetics: Corporate MissionCytokinetics: Corporate Mission

• Leverage cell biology based discovery technologies to exploit cytoskeletal pharmacology for the discovery and development of novel pharmaceuticals

• Manage technical and financial risks through building redundancies and breadth in all programs

• Conduct broad development programs for next generation pharmaceuticals that are designed to address liabilities of first generation therapeutics

• Commercialize proprietary pharmaceuticals with focus on sizeable and tractable commercial markets

Drug Discovery ParadigmDrug Discovery ParadigmThe Cytokinetics ApproachThe Cytokinetics Approach

> 2 GB of image data, feature data and

informatic reports generated per

compound

Proprietary Targets

500,000 Compounds

PUMA™ HTS

Cytometrix™ Cytometrix™ Cytometrix™ Cytometrix™ TechnologiesTechnologiesTechnologiesTechnologies

Optimized Hit

Animal Study

Lead

Development Candidate

Preclinical Development

INDApplication

Biochemical Hits

Informatics Needs at CytokineticsInformatics Needs at Cytokinetics

• Rapid analysis and delivery of results

• Real time data analysis for quality control

• User friendly data access

• Rapid deployment of new developments

• Ability to present high level summary data with an option of “drilling down”

Large amount of data generated throughout the drug discovery process requires

Spotfire™ Development at CytokineticsSpotfire™ Development at Cytokinetics

• DecisionSite Application– GuidesGuidesGuidesGuides allow scientists to easily follow steps to access the data

of interest, automatically applying visualization templates tailored for viewing the data

– DecisionSite Information Interaction Designer and Information Builder allows developers to easily construct complex queries from multiple data sources hiding data complexity and location from the end user

– ToolsToolsToolsTools provide sophisticated software solutions to be completely embedded and distributed from the Spotfire™ server

• Stand-alone integrated applications– Provide rich functionality while maintaining a common data

visualization platform for end users

– Well designed and documented Spotfire™ DecisionSite API makes development easy

Client systems running Spotfire™ DecisionSite

Screening TopologyScreening TopologyHigh Throughput

Screening Systems

Analysis servers

Reader files(XML)

Analysis results

LIMS

Spotfiretemplates

Corporate Network

Image files(TIFF)

Imaging MicroscopySystems

Cytometrix™Technologies

Spotfire servers(Development and Production)

Java, MatLab, C++LabVIEW, Excel etc.

Why Integrate with Spotfire™?Why Integrate with Spotfire™?

• Spotfire™ has grown to be the common data visualization tool across the company, in Data Analysis, Screening Operations, Quality Control, Assay Development, Chemistry, Biology

– “Pilot License” – development/several users

– “Departmental License” – expanded users

– “Biotech Company License” – rolled-out to Research

• Support for our primary development environments

– Infrastructure platform implemented with J2EE and Oracle

– Automation platform developed using LabVIEW

– Utilities implemented with Visual Basic

– Familiarity with XML and Oracle™

Integrating Spotfire™ with LabVIEW™Integrating Spotfire™ with LabVIEW™

Spotfire™:Real Time Analysis EnvironmentSpotfire™:Real Time Analysis Environment

Implementation MethodologyImplementation Methodology

• Establish connection with Spotfire™ DecisionSite (Application and Visualization ActiveX objects)

• Determine columns in current data set

• Respond to events (i.e. MarkedRecords) by obtaining information about which data points (records) were manipulated in the body of the event

• Update existing plots

• Create new plots

• Apply visualization templates

• Present data related to the selected data points using unique identifiers (i.e. barcode and well reference)

Functional Overview forClient ApplicationsFunctional Overview forClient Applications

Spotfire™ DecisionSite

Custom built clientsapplications

COM enabled communication

Spotfire Server

Cytokinetics Crunchers

ActivityBase™Database

Cytometrix™Technologies

Automation

Raw data

Spotfire™ reports

Spotfire™templates

Cytometrix™ CellularPhenotyping TechnologiesCytometrix™ CellularPhenotyping Technologies

• Automated cell handling and microscopy

• Advanced informatics quantify phenotype

• Profiles on- and off-target effects

• Comprehensive systems biology

• Systematically measures responses of individual cells to compounds of interest

• Dose response data used for compound comparison or classification

CytometrixTM TechnologiesCytometrixTM Technologies

Example of the Data Size in a Single Experiment– 6 cell lines– 2 marker sets (1 and 3 markers per set)– 2 time point– 83 compounds– 8 concentration per compound– run in triplicates

• 6*2*2*83*8*3 = 47,808 wells are screened

• 6*(1+3)*2*83*8*3 = 95,616 images are collected

• Expected about 800 cells per image on average, with total of 38,246,400 cells per experiment

• >170 GB of data generated for this experiment

Data Exploration: Cytokinetics DecisionSiteData Exploration: Cytokinetics DecisionSite

• DecisionSite application was developed with tools specific for Cytokinetics

Data Exploration: ToolsData Exploration: Tools

• Default Spotfire™ tools are moved/removed

• Tools are groups by user audience

• Access is controlled between difference applications

Technologies


• Different levels of data can be accessed

• Ease of navigationTechnologies


• Multiple databases can be accessed

• Data can be queried by experiment, compound, etc.

Data Exploration: Data OverviewData Exploration: Data OverviewNUM_OBJECT SNUM_OBJECT SNUM_OBJECT SNUM_OBJECT S

CONCENTRATION

CELLLINENAME - A498

MARKERSETNAME - OneStep

CELLLINENAME - A549


CELLLINENAME - DU145


CELLLINENAME - HUVEC


CELLLINENAME - SF268


CELLLINENAME - SKOV3


CELLLINENAME - A498

MARKERSETNAME - TriStain

CELLLINENAME - A549


CELLLINENAME - DU145


CELLLINENAME - HUVEC


CELLLINENAME - SF268


CELLLINENAME - SKOV3


0 1.... 2.... 5.00... 7.00... 8.99... 0.00... 0.0... 0.00... 0.... 0.... 0 1.... 2.... 5.00... 7.00... 8.99... 0.00... 0.0... 0.00... 0.... 0....

0200400600800

10001200

0200400600800

10001200

0200400600800

10001200

0200400600800

10001200

0200400600800

10001200

0200400600800

10001200

Large data sets can be summarized

Interfaces can be easily customized

Data Exploration: Data OverviewData Exploration: Data OverviewNUM_OBJECT SNUM_OBJECT SNUM_OBJECT SNUM_OBJECT S

CONCENTRATION2.000000010049... 7.399999... 1.499999... 1.9999... 2.50000000... 3.50000000... 4.0000... 4.49999999... 5.49999999... 5.99999... 6.599...

0

200

400

600

800

1000

1200

Users can “drill down” to each compound for a cell line at a time point

Data Exploration: Chemical InformationData Exploration: Chemical Information

Chemical tools are located together

Easily accessible

Data Exploration:Chemical InformationData Exploration:Chemical Information

•Multiple structure display

•‘Mouse over’ dynamic structural display

•Requires SMILES strings

Data Exploration: Biological Image InformationData Exploration: Biological Image Information

•Image related tools are located together

•CytoPix™ Viewer is a Visual Basic application

•Cyto Explorer is a Java plug-in

•Cyto Annotator is a Javascript tool

CytoPix™ Viewer: SetupCytoPix™ Viewer: Setup

•Users can access a number of variables

•Plate ID and well ID are selectable

CytoPix™ Viewer : Data SelectionCytoPix™ Viewer : Data Selection

Marked records are dynamically displayed in CytoPix™ Viewer

CytoPix™ Viewer : ImagesCytoPix™ Viewer : Images

Data Exploration:Cell Level InformationData Exploration:Cell Level Information

• Cell level data is available

• User can plot cell level data over the actual cell on the image with Cyto Explorer

• Cyto Explorer is easily configurable

Cyto Explorer: Drill DownCyto Explorer: Drill Down

Cell Data displayed on the

actual image, over actual cell

Cyto AnnotatorCyto Annotator

Allows users to record annotations into the Spotfire file

Conclusions: Spotfire™ inDrug DiscoveryConclusions: Spotfire™ inDrug Discovery

• KEY ADVANTAGES

– Visualization Framework

– Can be used across the drug discovery enterprise

– User Friendly

– Customizable

– Extendable

– Data Access Options

– Ease of Deployment

• POTENTIAL IMPROVEMENTS

– Large datasets

– Ability to integrate custom algorithms with Spotfire packages

– Dynamically append records

spotfire · conclusions: spotfire™ in drug discovery • key advantages – visualization...

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