Integrative Genomics and Chronic Disease Phenotypes:
modelling and simulation tools for clinicians

Computer analysis related to clinical problems is currently in a phase of accelerated growth. Some examples of the application of computer analysis in clinical practice are classification and prognosis of ovarian cancer, analysis of myocardial perfusion images and cardiograms, the development of a screening device for diagnosis of heart murmurs. Several projects in the European Union are implementing information technology-based services for diabetes management. However, all the approaches implemented in clinical practice to date use very limited datasets, despite the vast availability of data from various life science disciplines since the omics revolution. Only by integrating genomic, proteomic and metabolomic data, the knowledge useful for practical clinical applications could be obtained, thus achieving such ambitious goal as confronting complex human pathologies.

BioBridge proposes to do just that. We will focus on the application of simulation techniques on top of multilevel data, to create models for understanding at the systemic level, how molecular mechanisms are dynamically related with the complex diseases of interest. The project will explore/identify gaps of information, develop and apply standards for the transfer and filtering of data from existing molecular biology databases and new high-throughput experiments (microarray, in vivo metabolic profiling, and proteomics data) into metabolic models of the complex diseases. We are working hand in hand with SMEs from day one, with the express aim of creating protocols that will be commercially exploitable in order to standardise the analysis of relevant aspects of these diseases. This defines the main bioinformatic objective of BioBridge:
To develop software tools for integrated genomic, proteomic, metabolomic and kinetic analysis, which will build a bridge between clinical practice and basic science.

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The consortium brings together selected SMEs with complementary skills in the domains of semantic interoperability, heterogeneous data integration and simulation technologies to develop innovative tools to facilitate the interplay between omics data and clinical information. Synergies are ensured between SMEs and academic teams, as well as product quality assurance through generation of experimental data for model refinement and validation. BioBridge SMEs and academic teams together will facilitate a translational analysis of the test case: nitroso-redox imbalance of the cardiovascular system. The nitroso-redox disequilibrium causes O2 transport - O2 utilisation mismatching at tissue level in highly prevalent chronic disorders (chronic heart failure, chronic obstructive pulmonary disease and diabetes). It has been identified as a common pathway leading to systemic effects associated with poor prognosis and high use of healthcare resources. The produced simulation tools may help to identify appropriate biomarkers for non-invasive monitoring and offer a new tool for clinicians.

References

Talk at the Modelica Conference 2009 in Como, Italy.
Title: Creating a Bridge between Modelica and the Systems Biology Community. Abstract, Talk (PDF, 478kb) , Paper (PDF)

Talk at the Barcelona School on Biomedical Informatics 2009 in Barcelona, Spain.
Title: Data Integration and Knowledge Management Tutorial. PDF (3.9 MB)

The BioXM™ Knowledge Management Environment: a general and visually driven framework applied to the integration of large biological datasets.
Maier D, Kalus W, Wolff M, Kalko S G, Turan N, Falciani F and Losko S
Bioinformatics (2008) Submitted
Supplemental material:
Step by Step Tutorial (PDF, 1.8 MB)
Affymetrix Probe ID list for the Tutorial (TXT File, 239 KB)
R script pathway pca (5.4 KB)
R script pca t-test (1.5 KB)

Integration of transcriptomics data into systems biology modeling in the BioBridge portal. Gómez-Garrido A, Márquez S, Hernández-Sánchez M, Selivanov V, Cascante M,
Villà-Freixa J, and Kalko S G
CCIS Series (2008) Abstract