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Olivier Cinquin

Publications and source records attributed to Olivier Cinquin.

2 recordsLinked to original sources

POPE: Post Optimization Posterior Evaluation of Likelihood Free Models

In many domains, scientists build complex simulators of natural phenomena that encode their hypotheses about the underlying processes. These simulators can be deterministic or stochastic, fast or slow, constrained or unconstrained, and so on. Optimizing the simulators with respect to a set of parameter values is common practice, resulting in a single parameter setting that minimizes an objective subject to constraints. We propose a post optimization posterior analysis that computes and visualizes all the models that can generate equally good or better simulation results, subject to constraints. These optimization posteriors are desirable for a number of reasons among which easy interpretability, automatic parameter sensitivity and correlation analysis and posterior predictive analysis. We develop a new sampling framework based on approximate Bayesian computation (ABC) with one-sided kernels. In collaboration with two groups of scientists we applied POPE to two important biological simulators: a fast and stochastic simulator of stem-cell cycling and a slow and deterministic simulator of tumor growth patterns.

stat.ML↗

High-dimensional switches and the modeling of cellular differentiation

Many genes have been identified as driving cellular differentiation, but because of their complex interactions, the understanding of their collective behaviour requires mathematical modelling. Intriguingly, it has been observed in numerous developmental contexts, and particularly hematopoiesis, that genes regulating differentiation are initially co-expressed in progenitors despite their antagonism, before one is upregulated and others downregulated. We characterise conditions under which 3 classes of generic "master regulatory networks", modelled at the molecular level after experimentally-observed interactions (including bHLH protein dimerisation), and including an arbitrary number of antagonistic components, can behave as a "multi-switch", directing differentiation in an all-or-none fashion to a specific cell-type chosen among more than 2 possible outcomes. bHLH dimerisation networks can readily display coexistence of many antagonistic factors when competition is low (a simple characterisation is derived). Decision-making can be forced by a transient increase in competition, which could correspond to some unexplained experimental observations related to Id proteins; the speed of response varies with the initial conditions the network is subjected to, which could explain some aspects of cell behaviour upon reprogramming. The coexistence of antagonistic factors at low levels, early in the differentiation process or in pluripotent stem cells, could be an intrinsic property of the interaction between those factors, not requiring a specific regulatory system.

q-bio.MN↗