Computational tools and standards for integrative systems biology

Biological function is determined at the cell level by complex networks of nucleotides, proteins, carbohydrates and lipids involving molecular interactions such as ligand-protein, protein-protein, and protein-nucleotide binding. To quantitatively analyze the function of such complex systems requires biophysically-based mathematical models, and many such models have been developed by mathematical biologists around the world. We are working with other members of the Bioengineering Institute and other international colleagues to develop CellML, an extensible markup language (XML) standard, to encode these models. This allows models to be linked, through standard biological ontologies such as Biopax and the Gene Ontology, to bioinformatic databases such as the protein database (PDB), pathways (KEGG) and genome databases (NCBI, EBI, etc). We are helping to develop software tools for creating, running, editing and visualising models of biological systems. Additionally, there is a pressing need for standards for model encoding, availability and annotation within the systems biology and bioengineering communities. We are working with other scientists from around the world to develop and promote the adoption of such standards for biological models. 

Key Publications:

D. Hurley, H. Araki, Y. Tamada, B. Dunmore, D. Sanders, S. Humphreys, M. Affara, S. Imoto, K. Yasuda, Y. Tomiyasu, K. Tashiro, C. Savoie, V. Cho, S. Smith, S. Kuhara, S. Miyano, S. Charnock-Jones*, E.J. Crampin*, C. Print*
Gene Network Inference and Visualisation Tools for Biologists: Application to New Human Transcriptome Datasets
Nucleic Acids Research doi:10.1093/nar/GKR902

M.A. Mourão, J. Srividhya, P.E. McSharry, E.J. Crampin, S. Schnell
A Graphical User Interface for a Method to Infer Kinetics and Network Architecture (MIKANA)
PLoS ONE 6(11): e27534 doi:10.1371/journal.pone.0027534

S.M. Wimalaratne, M.D.B. Halstead, C.M. Lloyd, M.T. Cooling, E.J. Crampin, P.F. Nielsen
A method for visualizing CellML models
Bioinformatics 25, 3012-3019, 2009

S.M. Wimalaratne, M.D.B. Halstead, C.M. Lloyd, E.J. Crampin, P.F. Nielsen
Biophysical annotation and representation of CellML models
Bioinformatics 25, 2263-2270, 2009

S.M. Wimalaratne, M.D.B. Halstead, C.M. Lloyd, M.T. Cooling, E.J. Crampin, P.F. Nielsen 
Facilitating modularity and reuse: Guidelines for structuring CellML 1.1 models by isolating common biophysical concepts
Experimental Physiology 94 (5), 472-485, 2009 

J. Terkildsen, S.A. Niederer, E.J. Crampin, P.J. Hunter, N.P. Smith
Using Physiome standards to couple cellular functions for cardiac excitation-contraction
Experimental Physiology 93 (7), 919-929, 2008

M. Cooling, P.J. Hunter, E.J. Crampin
Modelling biological modularity with CellML
IET Systems Biology 2 (2), 73-79, 2008

N.P. Smith, E.J. Crampin, S.A. Niederer, J.B. Bassingthwaighte, D.A. Beard
Computational biology of cardiac myocytes: Proposed standards for the Physiome
Journal of Experimental Biology 210 (9), 1576-1583, 2007

N. Le Novere, A. Finney, M. Hucka, U. Bhalla, F. Campagne, J. Collado-Vides, E.J. Crampin, et al.
Minimum information requested in the annotation of biological models (MIRIAM)
Nature Biotechnology 23 (12), 1509-1515, 2005