Granatum_LiSIs_BIBE_2012_presentation_v4.0

A Workflow System for Virtual Screening in CancerChemoprevention

Kannas C. C., Achilleos K. G., Antoniou Z., Kalvari I., Kirmitzoglou I., Nicolaou C. A., Promponas V. J., Pattichis C. S.

13th November 2012IEEE 12th International Conference on BioInformatics &

BioEngineering

IEEE 12th International Conference on BioInformatics & BioEngineering

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About LiSIs platform Objectives What is LiSIs? Virtual Screening & Scientific Workflow Management Systems

LiSIs platform Virtual Screening Process Template Docking Models Predictive Models 3rd Party Tools The GRANATUM-LiSIs Platform

Concluding Remarks Acknowledgement Questions?

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Outline


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About LiSIs platform

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Provide a set of tools to create virtual screening process for the discovery of novel agents with desired properties.

Provide a set of tools to create data-driven models designed to predict biochemical properties of interest.

Provide an environment to create, update, store and share Scientific Workflows, that is accessible via a web interface.

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Objectives


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Life Science Informatics Scientific Workflow Management System

Computational Environment for Virtual Screening. Cancer Chemoprevention Research

Computational Tools borrowed from Drug Discovery Process.

GRANATUM project (http://www.granatum.org) Partially funded by the European Commission under the

Seventh Framework Programme in the area of Virtual Physiological Human (ICT-2009.5.3).

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What is LiSIs?

http://www.granatum.org/


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Virtual Screening Computational counterpart of biological screening. Goal: decrease the number of compounds physically

screened. Scientific Workflow Management Systems

(SWMS) Computational environments which facilitate the

design and execution of computational experiments (workflows).

Known SWMS: Taverna (http://www.taverna.org.uk/) KNIME (http://www.knime.org/ ) Galaxy (http://galaxy.psu.edu/)

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Virtual Screening & Scientific Workflow Management Systems

http://www.taverna.org.uk/

http://www.taverna.org.uk/

http://www.knime.org/

http://www.knime.org/

http://galaxy.psu.edu/


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LiSIs platformAvailable @ http://lisis.cs.ucy.ac.cy

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Virtual Screening Process Template

Input• GRANA

TUM platform File Loader

• File Readers

Preprocessing• File format

transformations

• Property Normalizer

• Descriptors Calculation

• Fragmentation

• Coordinates Calculation

• Protein Cleaner

Processing• Descriptor

Filters• Similarity

Search• Substructure

Search• Docking

Models• Predictive

Models

Postprocessing• Cleaning• Formatting• Merging

Output• Storage• Visualization


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Protein Preparation: Input

Protein.pdb file Process

Remove water molecules Add hydrogen atoms Calculate binding domain coordinates Clean protein from co-crystalized molecule

Output Modified protein.pdb file

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Docking Model PreparationDocking Model

Protein (pdb file)

Add Hydrogens

Remove H2

O

Calculate Pocket Coordinates

Separate reference ligand



Predictive Model Preparation

Predictive Model

Biological dataChemical dataAlgorithm

• Algorithm parameters



Predictive Model Preparation

• Chembl• Pubchem• Literature

Data gathering


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3rd Party Tools

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Galaxy is an open, web-based platform for data intensive biomedical research.

Free public server. Deploy locally. Deploy in a Cluster/Grid environment Deploy in the cloud (CloudMan Amazon EC2).


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Galaxy



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Galaxy configuration: Web Server(s) (Handle Users Requests) Job Manager (Job Management) Job Handler(s) (Job Execution)

Galaxy Tools are wrappers around command line applications.

Galaxy runs command line jobs at the background.

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Galaxy Integration Methodology


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A collection of cheminformatics and machine-learning software written in C++ and Python.

The core algorithms and data structures are written in C++. Wrappers are provided to use the toolkit from either Python or Java.

Additionally, the RDKit distribution includes a PostgreSQL-based cartridge that allows molecules to be stored in relational database and retrieved via substructure and similarity searches.

Features Overview RDKit Home Page

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RDKit

http://code.google.com/p/rdkit/wiki/FeatureOverview

http://www.rdkit.org/


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R is a language and environment for statistical computing and graphics.

R provides a wide variety of statistical (linear and nonlinear modelling, classical statistical tests, time-series analysis, classification, clustering, ...) and graphical techniques, and is highly extensible.

One of R's strengths is the ease with which well-designed publication-quality plots can be produced, including mathematical symbols and formulae where needed. Great care has been taken over the defaults for the minor design choices in graphics, but the user retains full control.

The R Project13th November 2012

The R Project

http://www.r-project.org/


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AutoDock Vina is a new open-source program for drug discovery, molecular docking and virtual screening, offering multi-core capability, high performance and enhanced accuracy and ease of use.

Features: Accuracy Compatibility with AutoDock Tools Ease of Use Flexible Side Chains

Some receptor side chains can be chosen to be treated as flexible during docking.

Speed AutoDock Vina

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AutoDock Vina

http://vina.scripps.edu/


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LiSIs platform DemoAvailable @ http://lisis.cs.ucy.ac.cy

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http://lisis.cs.ucy.ac.cy

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LiSIs platform Live Demo!!!

http://lisis.cs.ucy.ac.cy/


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Fill a current void in chemoprevention, and in general life sciences, research.

Enabling researchers to utilize state of the art computational techniques to search for the discovery of novel agents with desired properties.

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Concluding Remarks


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Acknowledgement

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Computer Science, UCYProf. C. S. PattichisC. A. Nicolaou (PhD)Z. AntoniouK. G. AchilleosBiological Sciences, UCYDr. V. J. PromponasI. KirmitzoglouI. Kalvari

Cancer Biology and Chemoprevention laboratory at Department of Biological Sciences, UCY.

Cancer Chemoprevention and Epigenomics Workgroup at German Cancer Research Center.

Members of the GRANATUM consortium.



Questions?

Granatum_LiSIs_BIBE_2012_presentation_v4.0

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