PROPRIETARY

SEURAT: A Tool for Navigating SAR

Authors: J Baxendale, K Scott, N Southall, T Nguyen, L Verma, H.

Wolters, Ajay

Celera Genomics45 W. Gude Drive

Rockville, MD 20850

ChemAxon UGM 19th May 2005

PROPRIETARY 2

What is SEURAT?

• Structured Exploratory Utility for Rational Therapeutics

• Named after Georges Seurat, founder of Pointillism

• Brings together many data points into complete picture

– Retrieves compounds and assay data from corporate DB

– Computes compound properties– Performs SAR analysis via

holistic views

PROPRIETARY 3

Why SEURAT?

• Diverse set of users

• Existing retrieval GUI (RS3) not well utilized– Database storage fine but GUI cumbersome– Users forced to hand craft presentations– Lack of incentive to capture data

• Commercial and free software did not meet our needs

PROPRIETARY 4

Reasons for Successful Adoption

• Highly knowledgeable full-time development team members

• Simple things simple, hard things possible

• Visual query interface that allows for incremental complication

• Facilitates presenting ideas to colleagues

• Orthogonal Perspectives from Tables – Table based (detail) views linked to holistic (pattern) views

• Something for everyone

PROPRIETARY 5

Simple things simple, hard things possible

PROPRIETARY 6

Incremental Complication “Decision script paradigm”1

1J. Med. Chem 1999 42 (26) 5369-5389, J. Med. Chem. 2002 45 (6) 1300-1312

PROPRIETARY 7

Incremental Complication “Replay Script Each Time”

PROPRIETARY 8

Facilitates presenting ideas to colleagues2

• Toolbar to easily control font, header height, grouping, cell height and cell detail

• Many export options to get the data into a more familiar form. As hard as we tried this was not avoidable

• Columns can be renamed, re-ordered and hidden. Rows can also be hidden

2Nature Biotechnology (23) (3) March 2005

PROPRIETARY 9

Orthogonal Perspectives from Tables - Holistic Views

• Holistic view that considers series rather than single compounds• Intelligent grouping of assays• Dynamic filtering• Extends 2-D views to higher dimensions using size, color, order

and label• Context of structure maintained using Marvin• Many views (Heat Map, Scatter Plot, Scatter Plot Matrix, Time

Series and Graphs) are linked. Selection or filtering in one is coordinated with all other views in real time

• Can support a reasonable number of data points ~100,000 before rendering starts to slow

• Can be sped up using Agile 2D

PROPRIETARY 10

Orthogonal Perspectives from Tables - Holistic Views1,3

1J. Med. Chem 1999 42 (26) 5369-5389, J. Med. Chem. 2002 45 (6) 1300-13123Views developed on top of the InfoVis toolkit ver 0.8 alpha 2 http://ivtk.sourceforge.net/

PROPRIETARY 11

Orthogonal Perspectives from Tables - SAR Matrix1

• Alternate but linked views of results:

– Tabular and most familiar– Matrix view with zooming and

cell coloring for emphasis of “hot spots”

• Can still organically grow the tabular view to better inform the matrix view

• We will see a demo later of SAR capabilities using a public dataset1

1J. Med. Chem 1999 42 (26) 5369-5389, J. Med. Chem. 2002 45 (6) 1300-1312

PROPRIETARY 12

Something for Everyone Other Views and ChemAxon Uses

Crystal Structure (Gleevec)4 Available Vendor Compounds

Lipinski Rule Prediction1 Functional Group Replacement

1J. Med. Chem 1999 42 (26) 5369-5389, J. Med. Chem. 2002 45 (6) 1300-13124J.Biol.Chem 279 pp. 55827 (2004)

Kinome Map Viewer

PROPRIETARY 13

Core Technology ConsiderationsChemAxon

• ChemAxon’s Marvin– All rendering

– Local sub-structure search emphasis

– Structure walking for SAR analysis

– Property predictions

• Oracle Cartridge– Substructure searches on vendor supplied libraries

– Library design and in house molecules for lead optimization.

PROPRIETARY 14

Core Technology ConsiderationsOther

• Use of Web Start was key to allowing deployment of application to large and growing user base.

• Application rather than applet for richness of interface.

• Java because we need to support several platforms– AIX, Linux, Max and Windows

• RMI to bridge into applications lacking a Java binding– home grown property predictors

– SAR searches

– similarity sorting

PROPRIETARY 15

Demo Time

• SAR• Presentation and collaboration enablers• Visualization extensions• Questions