HYBMOD toolbox for MATLAB is a prototype of a Hybrid Systems Biology framework that applies Hybrid Semiparametric Systems Theory to model complex biological systems. It compiles a library of hybrid modeling algorithms and hybrid model structures for Systems Biology problems. The following codes have been developed and may be available upon request:

• Hybrid metabolic flux analysis (HybMFA)
• Hybrid flux balance analysis (HybFBA)
• Projection to latent pathways (PLS)
• Hybrid ODE dynamical model (HybODE)
• Hybrid DDE dynamical model (HybDDE)
• Hybrid Nonlinear Partial Least Squares (HybNPLS)

These codes have no Graphical User Interface and are poorly documented. Licenses can be provided to Academia institutions upon a signed agreement. If you are interested please contact Rui Oliveira (rmo@fct.unl.pt)

Some examples of application of these tools can be found in the following publications:

• Moritz von Stosch, Rui Oliveira, Joana Peres and S. Feyo de Azevedo (2011) A hybrid modeling framework for PAT: Application to Bordetella pertussis cultures, Biotechnology Progress (in press)
• Ana P Teixeira, João ML Dias, Nuno Carinhas, Marcos Sousa, João J Clemente, António E Cunha, Moritz von Stosch, Paula M Alves, Manuel JT Carrondo, Rui Oliveira (2011) Cell functional enviromics: unravelling the function of environmental factors, BMC Systems Biology, 5: 92
• Carinhas N, Bernal V, Teixeira AP, Carrondo MJT, Alves PM, Oliveira ,R.(2011) Hybrid metabolic flux analysis: combining stoichiometric and statistical constraints to model the formation of complex recombinant products, BMC Systems Biolology, 5:34
• von Stosch M., Oliveira R., Peres J., Feyo de Azevedo S.; A novel identification method for hybrid (N)PLS dynamical systems with application to bioprocesses (2011), Expert Systems with Applications (in press)
• von Stosch, M., de Azevedo, SF, Oliveira, R., Modelling biochemical networks with intrinsic time delays: a hybrid semi-parametric approach, BMC Systems Biology (2010) 4:131
• Peres, J., Oliveira, R., de Azevedo, S.F. Bioprocess hybrid parametric/nonparametric modelling based on the concept of mixture of experts (2008) Biochemical Engineering Journal, 39 (1), pp. 190-206
• Teixeira, A.P., Carinhas, N., Dias, J.M.L., Cruz, P., Alves, P.M., Carrondo, M.J.T., Oliveira, R. Hybrid semi-parametric mathematical systems: Bridging the gap between systems biology and process engineering (2007) Journal of Biotechnology, 132 (4), pp. 418-425
• Santos, J.L.C., Hidalgo, A.M., Oliveira, R., Velizarov, S., Crespo, J.G. Analysis of solvent flux through nanofiltration membranes by mechanistic, chemometric and hybrid modelling (2007) Journal of Membrane Science , 300 (1-2), pp. 191-204
• Teixeira, A.P., Alves, C., Alves, P.M., Carrondo, M.J.T., Oliveira, R. Hybrid elementary flux analysis/nonparametric modeling: Application for bioprocess control (2007) BMC Bioinformatics , 8, art. no. 30
• Teixeira, A.P., Clemente, J.J., Cunha, A.E., Carrondo, M.J.T., Oliveira, R. Bioprocess iterative batch-to-batch optimization based on hybrid parametric/nonparametric models (2006) Biotechnology Progress , 22 (1), pp. 247-258
• Teixeira, A., Cunha, A.E., Clemente, J.J., Moreira, J.L., Cruz, H.J., Alves, P.M., Carrondo, M.J.T., Oliveira, R. Modelling and optimization of a recombinant BHK-21 cultivation process using hybrid grey-box systems (2005) Journal of Biotechnology, 118 (3), pp. 290-303
• Oliveira, R. Combining first principles modelling and artificial neural networks: A general framework (2004) Computers and Chemical Engineering, 28 (5), pp. 755-766