Penalized regression methods aim to retrieve reliable predictors among a large set of putative ones from a limited amount of measurements. In particular, penalized regression with singular penalty functions is important for sparse reconstruction algo
rithms. For large-scale problems, these algorithms exhibit sharp phase transition boundaries where sparse retrieval breaks down. Large optimization problems associated with sparse reconstruction have been analyzed in the literature by setting up corresponding statistical mechanical models at a finite temperature. Using replica method for mean field approximation, and subsequently taking a zero temperature limit, this approach reproduces the algorithmic phase transition boundaries. Unfortunately, the replica trick and the non-trivial zero temperature limit obscure the underlying reasons for the failure of a sparse reconstruction algorithm, and of penalized regression methods, in general. In this paper, we employ the ``cavity method to give an alternative derivation of the mean field equations, working directly in the zero-temperature limit. This derivation provides insight into the origin of the different terms in the self-consistency conditions. The cavity method naturally involves a quantity, the average local susceptibility, whose behavior distinguishes different phases in this system. This susceptibility can be generalized for analysis of a broader class of sparse reconstruction algorithms.
The concept of robustness of regulatory networks has been closely related to the nature of the interactions among genes, and the capability of pattern maintenance or reproducibility. Defining this robustness property is a challenging task, but mathem
atical models have often associated it to the volume of the space of admissible parameters. Not only the volume of the space but also its topology and geometry contain information on essential aspects of the network, including feasible pathways, switching between two parallel pathways or distinct/disconnected active regions of parameters. A general method is presented here to characterize the space of admissible parameters, by writing it as a semi-algebraic set, and then theoretically analyzing its topology and geometry, as well as volume. This method provides a more objective and complete measure of the robustness of a developmental module. As an illustration, the segment polarity gene network is analyzed.
The role of post-translational modification of histones in eukaryotic gene regulation is well recognized. Epigenetic silencing of genes via heritable chromatin modifications plays a major role in cell fate specification in higher organisms. We formul
ate a coarse-grained model of chromatin silencing in yeast and study the conditions under which the system becomes bistable, allowing for different epigenetic states. We also study the dynamics of the boundary between the two locally stable states of chromatin: silenced and unsilenced. The model could be of use in guiding the discussion on chromatin silencing in general. In the context of silencing in budding yeast, it helps us understand the phenotype of various mutants, some of which may be non-trivial to see without the help of a mathematical model. One such example is a mutation that reduces the rate of background acetylation of particular histone side-chains that competes with the deacetylation by Sir2p. The resulting negative feedback due to a Sir protein depletion effect gives rise to interesting counter-intuitive consequences. Our mathematical analysis brings forth the different dynamical behaviors possible within the same molecular model and guides the formulation of more refined hypotheses that could be addressed experimentally.
