|Task 3.1 Biomedical applications|
Under the bioinformatics and medical informatics terms, this proposal considers the research and development on biology and medicine using advanced information and communication technologies (ICT). Since there are many different complementary meanings, we will refer as “biomedicine” all the activities related to bioinformatics and medical informatics.
|DESCRIPTION OF THE WORK|
GATE (Geant4 Application for Tomographic Emission)Radiotherapy and brachytherapy use ionizing radiations to treat cancer. Before each treatment, physicians and physicists plan the treatment using analytical planning systems and medical images data of the tumour area.
These analytical solutions simplify the problem not considering the different density of the tissues and leading to a significant inaccuracy. In order to treat patients with the best accuracy, Monte Carlo simulations are today the best tool to model and plan the tumour treatment for complex requirements.
GATE is a C++ platform based on the Monte Carlo Geant4 software.
It has been typically designed to model nuclear medicine applications, such as the Positron Emission Tomography (PET) and the Single Positron Emission Computed Tomography (SPECT) among the OpenGATE collaboration. Its functionalities, combined to its ease of use, make this platform also adequate for radiotherapy and brachytherapy treatment planning.
WISDOM (Wide In Silico Docking of Malaria)
The objective of the WISDOM is the creation of new inhibitors for a family of proteins produced by Plasmodium falciparum. This protozoan parasite causes malaria and affects around three hundred million people and more than 4 thousand people die daily in the world.
Drug resistance has emerged for all classes of antimalarials except artemisinins. The main reason is that the available drugs focus on a limited number of biological targets, producing a cross-resistance to antimalarials. There is a consensus that substantial scientific effort is needed to identify new targets for antimalarials.
The main problem is that the development of new drugs with new targets is a costly and lengthy process, and the economic profit is not clear for the drug manufacturers.
This application consists on the deployment of a high throughput virtual screening platform in the perspective of in silico drug discovery for neglected diseases. The WISDOM platform performs a High-Throughput virtual Docking of million of chemical compounds available in the databases of ligands to several targets of Plasmepsin.
BLAST (Basic Local Alignment Searching Tool)
One of the most important efforts on the analysis of the genome is the study of the functionality of the different genes and regions. Sequence alignments provide a powerful way to compare novel sequences with previously characterized genes. Both functional and evolutionary information can be inferred from well designed queries and alignments.
BLAST finds regions of local similarity between sequences. The program compares nucleotide or protein sequences to sequence databases and calculates the statistical significance of matches.
This process of finding homologous of sequences is a very computationally-intensive process. The size of the non-redundant databases currently available increases daily, reaching the size of more than a gigabyte. Searching alignment of a single sequence is not a costly task, but normally, thousands of sequences are searched at the same time. Moreover, since the databases are periodically updated, it will be convenient to periodically update the results of previous studies.
A phylogeny is a reconstruction of the evolutionary history of a group of organisms. Phylogenies are used throughout the life sciences, as they offer a structure around which to organize the knowledge and data accumulated by researchers.
The inference of phylogenies with computational methods is widely used in medical and biological research and has many important applications, such as gene function prediction, drug discovery and conservation biology. Bayesian inference is a powerful mathematical method which is implemented in the program MrBayes for estimating phylogenetic trees that are based on the a posteriori probability distribution of the trees.
Compared to other methods, Bayesian inference takes full advantage of the information contained in the alignment of DNA sequences when estimating phylogenies because it can even make use of morphological data. The complexity of large-scale phylogeny studies, represents a true computational grand challenge. Due to the nature of Bayesian inference, the simulation can be prone to entrapment in local maxima. To overcome local maxima and achieve better estimation, the MrBayes program has to run for millions of iterations (generations) that require a large amount of computation time.
The Ibero-American Portal of Bioinformatics (http://portal-bio.ula.ve) installed at the National Centre for Scientific Computation (CeCalCULA) of the Universidad de Los Andes in Venezuela is an initiative for the spreading of findings in the Bioinformatics area in Venezuela and in other Spanish speaking countries developed before EELA starting date.
This portal of portals is the result of the incorporation of several servers developed at CeCalCULA which aims to create on-line academic and research communities.
It also has several on-line applications for registered users and, the number of which expects to increase by joining EELA. Thus, the availability of an independent Grid-enabled version integrated on the Bioinformatics Portal will provide registered users with results in a shorter time within the frame of the BLAST application or a Grid service for the parallelised version of MrBayes.
For the estimation of resources needed, it must be considered that not all users are normally working simultaneously on the portal. Peak usage is estimated in the order of 50-100 simultaneous users. Own resources of the Bioinformatics portal (10 Opteron processors and 36 GBytes of RAM) are adequate for setting up the basic services, but will not be enough to deploy a production system for mpiBLAST or MrBayes. The linkage of the portal to the EELA Grid is necessary to deal with the computational demand estimated. The 24 Mbps network connection of the centre will be in September 2006, which will not penalise the performance if computing is moved within the Grid.
The application EMBOSS is being ported to the Grid creating in this way a new application called GrEMBOSS. With this free Open Source software analysis package specially developed for the needs of the molecular biology user community EELA will keep on working in the biomedical field as well as increasing their users. The versions that will be ported are the latest released, i.e, 4.0 and 4.1 as well as the databases that will be stored in the Storage Elements and the LFC by means of the GFAL library.
The script for the submission of jobs from a UI makes all the necessary commands and deals with the databases and the EMBOSS tool in order to obtain the final results transparently for the user.
GAMOS / MIRaS
New tools developed for the simulation of the effects of the radiation in the human body have joined recently the EELA Project. They are GAMOS and MIRaS, which will complete the scope of GATE since they are also based on GEANT4 and Monte Carlo simulations, but their application is not in the field of Nuclear Medicine. The main lines of activities are involved in medical imaging, radiotheraphy, medical computing, biomedical engineering and radio protection to the patient. Thus, the aim is to offer to the medical, physic, medical-physic and engineer community open tools to design its own medical imaging systems, verification and planification of treatment diseases, and in general to understand all the physics implicated in many areas of the healthcare.
The EELA proposal focuses on transferring the organisational model of the European project EGEE into the Latin-American Countries. Thus it shares many interests and strategies and exploits the know-how already generated in the EGEE project. The experience and the large amount of information concerning the groups in Latin America should be also considered as an important counterpart to the EGEE project.
References- Project EELA, Technical Annex I. Available at: http://www.eu-eela.org/
- EGEE, http://www.eu-egee.org
- EGEE BioMed Applications, http://egee-na4.ct.infn.it/biomed/applications.html
- HealthGrid collaboration, ?HealthGrid White Paper?, http://whitepaper.healthgrid.org/
- S. Jan et al., "GATE: a simulation toolkit for PET and SPECT", submitted to Phys. Med. Biol.
- OpenGATE collaboration, http://www-lphe.epfl.ch/~PET/research/gate/
- L. Maigne, GATE Application in EGEE http://egee-na4.ct.infn.it/biomed/gate.html
- Wide In Silico Docking Of Malaria (WISDOM), home page http://wisdom.healthgrid.org
- BLAST: http://www.ncbi.nlm.nih.gov/Education/BLASTinfo/information3.html
- BLAST Processing service: http://www.ncbi.nlm.nih.gov/blast/
- mpiBLAST http://mpiblast.lanl.gov/
- NCBI BLAST home page http://www.ncbi.nlm.nih.gov/blast/
- mpiBLAST: Open-Source Parallel BLAST home page, http://mpiblast.lanl.gov/
- K. Lesheng , "Phylogenetic Inference Using Parallel Version of MrBayes"
- F. Ronquist, J. P. Huelsenbeck, "MrBayes 3: Bayesian phylogenetic inference", Bioinformatics 19 12, 1572?1574 (2003)
- Requirements of the BioMed VO, http://egee-na4.ct.infn.it/requirements/
- L.Maigne et al., "Parallelization of Monte Carlo Simulations and Submission to a Grid Environment", Parallel Processing Letters journal 14 2, 177-196 (2004)
- GEANT4, http://geant4.web.cern.ch/geant4/
- The LHCb experiment, http://lhcb-public.web.cern.ch/lhcb-public/default.htm
- D. Navarro "Epidemiología de las enfermedades del tiroides en Cuba", Rev Cubana Endocrinología 15 (2004)
- J. Alert, J. Jiménez, "Tendencias del tratamiento radiante en los tumores del sistema nervioso central", Rev Cubana Med 43 2-3 (2004)
- J.L. Valenciaga Rodríguez et al., "Cáncer de tiroides en Cuba: estudio de 14 años" Revista Cubana de Endocrinología 16 3 (2005)
- National Cancer Institute (NCI) May 2005, http://clinicaltrial.gov
- SIMDAT, http://www.scai.fraunhofer.de/simdat.html
- SwissBioGRID, http://www.swissbiogrid.com
- The Swiss Institue of Bioinformatics, http://www.isb-sib.ch/
- INSTRUIRE, Auvergrid, http://www.auvergrid.fr
- CampusGRID, http://www.campusgrid.upv.es
- V. Breton, "Grid added value to fight neglected diseases", Wisdom Open Day, http://www.scai.fraunhofer.de/fileadmin/download/vortraege/wisdom/wisdom_breton.pdf
- A. Brandling-Bennet, F. Penheiro, "Infectious Diseases in Latin America and the Caribbean: Are They Really Emerging and Increasing?", Emerging Infectious Diseases 2 1, 59-61 (1996)
- National Centre for Biotechnology Information (NCBI) http://www.ncbi.nlm.nih.gov/
- Grid Protein Sequence Analysis web portal, http://gpsa.ibcp.fr
- CeCalCULA, http://www.cecalc.ula.ve
Links to slides presented in conferences, papers, posters, etc. can be found here:
- WP3 DOCUMENTS
- EELA DOCUMENTS