1. A Workflow System for Virtual
Screening in Cancer
Chemoprevention
Kannas C. C., Achilleos K. G., Antoniou Z., Kalvari I., Kirmitzoglou
I., Nicolaou C. A., Promponas V. J., Pattichis C. S.
13th November 2012
IEEE 12th International Conference on BioInformatics &
BioEngineering

2. Outline
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?
IEEE 12th International Conference on BioInformatics &
2 13th November 2012
BioEngineering

3. About LiSIs platform
IEEE 12th International Conference on BioInformatics &
3 13th November 2012
BioEngineering

4. Objectives
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.
IEEE 12th International Conference on BioInformatics &
4 13th November 2012
BioEngineering

5. What is LiSIs?
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).
IEEE 12th International Conference on BioInformatics &
5 13th November 2012
BioEngineering

6. Virtual Screening & Scientific
Workflow Management Systems
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/)
IEEE 12th International Conference on BioInformatics &
6 13th November 2012
BioEngineering

7. Available @ http://lisis.cs.ucy.ac.cy
LiSIs platform
IEEE 12th International Conference on BioInformatics &
7 13th November 2012
BioEngineering

8. Virtual Screening Process
Template
Output
Postprocessing •Storage
•Visualization
•Cleaning
•Formatting
Processing
•Merging
•Descriptor Filters
•Similarity Search
Preprocessing •Substructure
Search
•File format •Docking Models
transformations
•Predictive Models
•Property
Normalizer
Input •Descriptors
•GRANATUM Calculation
platform File •Fragmentation
Loader •Coordinates
•File Readers Calculation
•Protein Cleaner
IEEE 12th International Conference on BioInformatics &
8 13th November 2012
BioEngineering

9. Docking Model Preparation
Protein (pdb file)
Add Hydrogens
Protein Preparation: Remove H2O Docking
Input Model
Protein.pdb file Calculate Pocket
Process Coordinates
Remove water molecules Separate reference
Add hydrogen atoms ligand
Calculate binding domain coordinates
Clean protein from co-crystalized molecule
Output
Modified protein.pdb file
IEEE 12th International Conference on BioInformatics &
9 13th November 2012
BioEngineering

10. Predictive Model Preparation
Chemical
data
Algorithm
Biological
•Algorithm
data parameters
Predictive
Model
IEEE 12th International Conference on BioInformatics &
10 13th November 2012
BioEngineering

11. Predictive Model Preparation
Model
Predictions
•Chembl Training •Cross-Validation
•Pubchem •Independent
•Feature extraction / validation using •Predict biological
•Literature
selection separate datasets properties of
•Various algorithms compounds
(kNN, SVM, Random •E.g. Toxicity, ER-
Forest, Decision Trees) binding activity
Data Model
gathering Validation
IEEE 12th International Conference on BioInformatics &
11 13th November 2012
BioEngineering

12. 3rd Party Tools
IEEE 12th International Conference on BioInformatics &
12 13th November 2012
BioEngineering

13. Galaxy
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).
http://galaxy.psu.edu/
IEEE 12th International Conference on BioInformatics &
13 13th November 2012
BioEngineering

14. Galaxy Integration Methodology
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.
IEEE 12th International Conference on BioInformatics &
14 13th November 2012
BioEngineering

15. RDKit
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
IEEE 12th International Conference on BioInformatics &
15 13th November 2012
BioEngineering

16. The R Project
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 Project
IEEE 12th International Conference on BioInformatics &
16 13th November 2012
BioEngineering

17. AutoDock Vina
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
IEEE 12th International Conference on BioInformatics &
17 13th November 2012
BioEngineering

18. Available @ http://lisis.cs.ucy.ac.cy
LiSIs platform Demo
IEEE 12th International Conference on BioInformatics &
18 13th November 2012
BioEngineering

19. LiSIs platform Live Demo!!!
http://lisis.cs.ucy.ac.cy
IEEE 12th International Conference on BioInformatics &
19 13th November 2012
BioEngineering

20. Concluding Remarks
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.
IEEE 12th International Conference on BioInformatics &
20 13th November 2012
BioEngineering

21. Acknowledgement
Computer Science, UCY Cancer Biology and
Prof. C. S. Pattichis Chemoprevention
C. A. Nicolaou (PhD) laboratory at Department of
Biological Sciences, UCY.
Z. Antoniou
Cancer Chemoprevention
K. G. Achilleos and Epigenomics Workgroup
Biological Sciences, UCY at German Cancer Research
Dr. V. J. Promponas Center.
I. Kirmitzoglou Members of the GRANATUM
I. Kalvari consortium.
IEEE 12th International Conference on BioInformatics &
21 13th November 2012
BioEngineering

22. Questions?
IEEE 12th International Conference on BioInformatics &
22 13th November 2012
BioEngineering