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Research

I’m a bioinformatician (computer scientist by training), interested in deciphering the mechanisms underlying complex biological systems (AKA “Systems Biology”). In particular, we want to turn mechanistic details into mathematical models which can be used to highlight their limitations (gaps and inconsistencies), and to guide experimental design.

My main contributions focus on handling “large” models in qualitative dynamical models (AKA logical models). I could work on complementary aspects:

  • Formal methods for handling large models: model reduction and static analysis.
  • Software implementation, especially GINsim.
  • Applications to biological systems: cell cycle, Th differentiation.

Methods for handling large logical models

My main methodological contributions rely on the use of Multivalued Decision Diagrams (MDDs) to represent logical functions. By using MDDs, we could design an efficient method to find all possible stable states of a model, as well as to extract some information on the most important feedback circuits in a model. Later on, we proposed a reduction method, allowing to remove some components while preserving important dynamical properties. I was also involved in the definition of Hierarchical Transition Graphs, a novel compact representation of the dynamics, inspired by the graph of Strongly Connected Components.

Decision diagrams for the representation and analysis of logical models of genetic networks
A. Naldi, D. Thieffry, C. Chaouiya (2007)
Computational Methods in Systems Biology. Lecture Notes in Computer Science 4695:233—247 [doi:10.1007/978-3-540-75140-3_16]
Dynamically consistent reduction of logical regulatory graphs
A. Naldi, E. Remy, D. Thieffry, C. Chaouiya (2011)
Theoretical Computer Science 412(21):2207—2218 [doi:10.1016/j.tcs.2010.10.021]
Dynamical modeling and analysis of large cellular regulatory networks.
D. Bérenguier, C. Chaouiya, P.T. Monteiro, A. Naldi, E. Remy, D. Thieffry, L. Tichit (2013)
Chaos 23(2):025114 [doi:10.1063/1.4809783] [pubmed:23822512] Open Access

Software tools

I am the main developer of the GINsim software for the definition and analysis of logical models. This tool provides a graphical interface for model design and a number of analytical tools, including my formal works on logical models. It also provides import/export bridges to other software tools. GINsim has been used to study dozens of models, either through collaborations or by independent researchers.

I am also involved in the CoLoMoTo effort to improve the exchange of discrete models. This effort led to the qual extension for SBML and the bioLQM toolbox.

Logical modelling of regulatory networks with GINsim 2.3.
A. Naldi, D. Berenguier, A. Fauré, F. Lopez, D. Thieffry, C. Chaouiya (2009)
Bio Systems 97(2):134—9 [doi:10.1016/j.biosystems.2009.04.008] [pubmed:19426782]
SBML qualitative models: a model representation format and infrastructure to foster interactions between qualitative modelling formalisms and tools.
C. Chaouiya, D. Bérenguier, S.M. Keating, A. Naldi, M.P. van Iersel, N. Rodriguez, A. Dräger, F. Büchel, T. Cokelaer, B. Kowal, B. Wicks, E. Gonçalves, J. Dorier, M. Page, P.T. Monteiro, A. von Kamp, I. Xenarios, H. de Jong, M. Hucka, S. Klamt, D. Thieffry, N. Le Novère, J. Saez-Rodriguez, T. Helikar (2013)
BMC Systems Biology 7(1):135 [doi:10.1186/1752-0509-7-135] [pubmed:24321545] Open Access

Logical models of biological systems

Qualitative models have been applied to a wide range of biological networks, I have been personnaly involved mainly in the study of cell cycle, and differentiation of T helper cells.

Dynamical analysis of a generic Boolean model for the control of the mammalian cell cycle.
A. Fauré, A. Naldi, C. Chaouiya, D. Thieffry (2006)
Bioinformatics 22(14):e124—31 [doi:10.1093/bioinformatics/btl210] [pubmed:16873462] Open Access
Diversity and plasticity of Th cell types predicted from regulatory network modelling.
A. Naldi, J. Carneiro, C. Chaouiya, D. Thieffry (2010)
PLoS Computational Biology 6(9):e1000912 [doi:10.1371/journal.pcbi.1000912] [pubmed:20824124] Open Access

Genomics and metabolism

During my postdoctoral work in Lausanne (Switzerland), I was involved in the study of genomics data (microarray and ChIP-seq) in the context of metabolic processes.

Genome-Wide Analysis of SREBP1 Activity around the Clock Reveals Its Combined Dependency on Nutrient and Circadian Signals.
F. Gilardi, E. Migliavacca, A. Naldi, M. Baruchet, D. Canella, G. Le Martelot, N. Guex, B. Desvergne (2014)
PLoS Genetics 10(3):e1004155 [doi:10.1371/journal.pgen.1004155] [pubmed:24603613] Open Access

Related publications are in preparation.