The UTC Chair of Mathematical Modeling and Systems Biology for Predictive Toxicology, currently held by Frédéric Y. Bois, aims to develop:
  1. A cursus in bioinformatics, biomathematics and biostatistics at UTC (see Teaching)
  2. Research in systems biology, bioinformatics and related areas (Research)
  3. A dialogue between biologists, mathematicians and decision makers (Publications and Links)
Updates on our latest activities:

New software available: Graph_Sampler

posted Jan 15, 2015, 4:20 AM by Frederic Bois

On our software page you will now find the code and manual for Graph_Sampler, a tool for simulating structured random networks and for performing Bayesian inference on networks' structures.

Open post-doctoral research position: Endocrine disruption

posted Nov 26, 2014, 10:02 AM by Frederic Bois   [ updated Nov 26, 2014, 10:04 AM ]

We are recruiting a motivated post-doctoral researcher to further develop the steroidogenesis model we started working on with Nadia Quignot. See the attached pdf (English version and version française) for more information.

Integration of Omics Data and Systems Biology Modeling

posted Dec 20, 2013, 1:55 AM by Frederic Bois   [ updated Aug 11, 2014, 7:31 AM ]

Integration of Omics Data and Systems Biology Modeling: Effect of Cyclosporine A on the Nrf2 Pathway in Human Renal Kidneys Cells

Jérémy Hamon, Paul Jennings, Frederic Y. Bois

In a recent paper, Wilmes et al. demonstrated a qualitative integration of omics data streams to gain a mechanistic understanding of cyclosporine A toxicity. One of their major conclusions was that cyclosporine A strongly activates the nuclear factor (erythroid-derived 2)-like 2 pathway (Nrf2) in renal proximal tubular epithelial cells exposed in vitro. We pursue here the analysis of those data with a quantitative integration of omics data with a differential equation model of the Nrf2 pathway. That was done in two steps: (i) Modeling the in vitro pharmacokinetics of cyclosporine A (exchange between cells, culture medium and vial walls) with a minimal distribution model. (ii) Modeling the time course of omics markers in response to cyclosporine A exposure at the cell level with a coupled PK-systems biology model. Posterior statistical distributions of the parameter values were obtained by Markov chain Monte Carlo sampling. Data were well simulated, and the known in vitro toxic effect EC50 was well matched by model predictions. The integration of in vitro pharmacokinetics and systems biology modeling gives us a quantitative insight into mechanisms of cyclosporine A oxidative-stress induction, and a way to predict such a stress for a variety of exposure conditions.
BMC Systems Biology

A contribution of arXiv

posted Nov 28, 2013, 4:16 AM by Frederic Bois   [ updated Jan 9, 2014, 5:34 AM ]

Probabilistic generation of random networks taking into account information on motifs occurrence

Frederic Y. Bois, Ghislaine Gayraud

Because of the huge number of graphs possible even with a small number of nodes, inference on network structure is known to be a challenging problem. Generating large random directed graphs with prescribed probabilities of occurrences of some meaningful patterns (motifs) is also difficult. We show how to generate such random graphs according to a formal probabilistic representation, using fast Markov chain Monte Carlo methods to sample them. As an illustration, we generate realistic graphs with several hundred nodes mimicking a gene transcription interaction network in Escherichia coli.


GNU's 30th anniversary!

posted Sep 7, 2013, 11:30 PM by Frederic Bois

Thirty years ago, Richard Stallman published the announcement that would launch the free software movement.
See the Web page of the Free Software Foundation and learn about the associated events.

[ Celebrate 30 years of GNU! ]

Opened post-doctoral research position

posted May 2, 2013, 8:35 AM by Frederic Bois   [ updated May 14, 2013, 5:00 AM ]

We are recruiting a motivated post-doctoral researcher to develop hybrid (differential/boolean) stochastic models of epithelial barriers.
Our group focuses on predictive toxicology for therapeutic drugs or general chemicals. Experimentalists develop miniaturized in vitro exposure systems (bioartificial organs on microfluidic biochips) and generate omics data to characterize the state of those systems. A challenge is to  develop the corresponding mechanistic toxicokinetic and toxicodynamic models and to calibrate them formally with such data, in a Bayesian framework.

See the attached pdf (English version)

L’Université de Technologie de Compiègne recrute un(e) chercheur contractuel(le) dans le cadre d’une mission post doctorale associée à la Chaire de Modélisation Mathématique et Biologie Systémique, à l'UMR CNRS 7338 du département de Génie Biologique.
Nos travaux portent sur la prédiction de la toxicité des molécules chimiques. Pour y parvenir, nous développons des systèmes d’exposition in vitro (organes bioartificiels au sein de biopuces microfluidiques, systèmes de barrières physiologiques), une modélisation de la toxicocinétique et des effets cellulaires in vivo et in vitro, évalués sur la base de méthodes omiques.
Le travail post-doctoral se focalisera sur le développement de modèles stochastiques hybrides (différentiels/booléens) décrivant la mise en place des barrières épithéliales. Ces modèles seront  calibrés à l'aide des données obtenues dans le projet.

Voir le pdf joint (version française)

CSU on the move

posted Apr 12, 2013, 5:31 AM by Frederic Bois

Brad Reisfeld and his Systems and Computational Biology Research Group at Colorado State University have launched
DoseSim, a simulation software based on our brainchild, GNU MCSim. DoseSim has a nice interface and runs on PCs...

By the way, check also F. Bois' chapter on Bayesian Statistics in  Brad Reisfeld's and Arthur Mayeno's two-volume book as part of the Humana Press “Methods in Molecular Biology” series entitled “Computational Toxicology”. It is now available from Springer and major bookstores, including amazon.com.

Visit of Andrew Gelman

posted Apr 11, 2013, 6:00 AM by Frederic Bois   [ updated Apr 12, 2013, 5:10 AM ]

Andrew Gelman (Columbia University) will visit us for 6 months this year. We will work with us on his latest creature: Stan, and it will not be just cosmetics!

Release of GNU MCSim v. 5.5.0

posted Mar 19, 2013, 5:57 AM by Frederic Bois

Version 5.5.0 of MCsim is available at http://ftp.gnu.org/gnu/mcsim/
See the official web page at http://www.gnu.org/software/mcsim/

The latest version of the model generator "mod" can now
generate C code directly usable with the R package deSolve. Simply use the "-R" option for that.

Version 5.5.0 also fixes a potential security problem at the installation phase (originating from automake).

Advancing alternatives to animal experiments for endocrine perturbation

posted Dec 10, 2012, 6:28 AM by Frederic Bois   [ updated Nov 26, 2014, 10:05 AM ]

A finely tuned balance between estrogens and androgens controls reproductive functions, and the last step of steroidogenesis plays a key role in maintaining that balance. Environmental toxicants are a serious health concern, and numerous studies have been devoted to studying the effects of endocrine disrupting chemicals (EDCs). The effects of EDCs on steroidogenic enzymes may influence steroid secretion and thus lead to reproductive toxicity. To predict hormonal balance disruption on the basis of data on aromatase activity and mRNA level modulation obtained in vitro on granulosa cells, we developed a mathematical model for the last gonadal steps of the sex steroid synthesis pathway. The model can simulate the ovarian synthesis and secretion of estrone, estradiol, androstenedione, and testosterone, and their response to endocrine disruption. The model is able to predict ovarian sex steroid concentrations under normal estrous cycle in female rat, and ovarian estradiol concentrations in adult female rats exposed to atrazine, bisphenol A, metabolites of methoxychlor or vinclozolin, and letrozole.

The report of this work by Nadia Quignot and Frederic Y. Bois is in press in PLOS ONE (http://dx.plos.org/10.1371/journal.pone.0053891)

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