Microbial metabolic networks perform the basic function of harvesting energy from nutrients to generate the work and free energy required for survival, growth and replication. The robust physiological outcomes they generate across vastly different or
ganisms in spite of major environmental and genetic differences represent an especially remarkable trait. Most notably, it suggests that metabolic activity in bacteria may follow universal principles, the search for which is a long-standing issue. Most theoretical approaches to modeling metabolism assume that cells optimize specific evolutionarily-motivated objective functions (like their growth rate) under general physico-chemical or regulatory constraints. While conceptually and practically useful in many situations, the idea that certain objectives are optimized is hard to validate in data. Moreover, it is not clear how optimality can be reconciled with the degree of single-cell variability observed within microbial populations. To shed light on these issues, we propose here an inverse modeling framework that connects fitness to variability through the Maximum-Entropy guided inference of metabolic flux distributions from data. While no clear optimization emerges, we find that, as the medium gets richer, Escherichia coli populations slowly approach the theoretically optimal performance defined by minimal reduction of phenotypic variability at given mean growth rate. Inferred flux distributions provide multiple biological insights, including on metabolic reactions that are experimentally inaccessible. These results suggest that bacterial metabolism is crucially shaped by a population-level trade-off between fitness and cell-to-cell heterogeneity.
We propose a novel approach to the inverse Ising problem which employs the recently introduced Density Consistency approximation (DC) to determine the model parameters (couplings and external fields) maximizing the likelihood of given empirical data.
This method allows for closed-form expressions of the inferred parameters as a function of the first and second empirical moments. Such expressions have a similar structure to the small-correlation expansion derived by Sessak and Monasson, of which they provide an improvement in the case of non-zero magnetization at low temperatures, as well as in presence of random external fields. The present work provides an extensive comparison with most common inference methods used to reconstruct the model parameters in several regimes, i.e. by varying both the network topology and the distribution of fields and couplings. The comparison shows that no method is uniformly better than every other one, but DC appears nevertheless as one of the most accurate and reliable approaches to infer couplings and fields from first and second moments in a significant range of parameters.
Efficient feature selection from high-dimensional datasets is a very important challenge in many data-driven fields of science and engineering. We introduce a statistical mechanics inspired strategy that addresses the problem of sparse feature select
ion in the context of binary classification by leveraging a computational scheme known as expectation propagation (EP). The algorithm is used in order to train a continuous-weights perceptron learning a classification rule from a set of (possibly partly mislabeled) examples provided by a teacher perceptron with diluted continuous weights. We test the method in the Bayes optimal setting under a variety of conditions and compare it to other state-of-the-art algorithms based on message passing and on expectation maximization approximate inference schemes. Overall, our simulations show that EP is a robust and competitive algorithm in terms of variable selection properties, estimation accuracy and computational complexity, especially when the student perceptron is trained from correlated patterns that prevent other iterative methods from converging. Furthermore, our numerical tests demonstrate that the algorithm is capable of learning online the unknown values of prior parameters, such as the dilution level of the weights of the teacher perceptron and the fraction of mislabeled examples, quite accurately. This is achieved by means of a simple maximum likelihood strategy that consists in minimizing the free energy associated with the EP algorithm.
Contact-tracing is an essential tool in order to mitigate the impact of pandemic such as the COVID-19. In order to achieve efficient and scalable contact-tracing in real time, digital devices can play an important role. While a lot of attention has b
een paid to analyzing the privacy and ethical risks of the associated mobile applications, so far much less research has been devoted to optimizing their performance and assessing their impact on the mitigation of the epidemic. We develop Bayesian inference methods to estimate the risk that an individual is infected. This inference is based on the list of his recent contacts and their own risk levels, as well as personal information such as results of tests or presence of syndromes. We propose to use probabilistic risk estimation in order to optimize testing and quarantining strategies for the control of an epidemic. Our results show that in some range of epidemic spreading (typically when the manual tracing of all contacts of infected people becomes practically impossible, but before the fraction of infected people reaches the scale where a lock-down becomes unavoidable), this inference of individuals at risk could be an efficient way to mitigate the epidemic. Our approaches translate into fully distributed algorithms that only require communication between individuals who have recently been in contact. Such communication may be encrypted and anonymized and thus compatible with privacy preserving standards. We conclude that probabilistic risk estimation is capable to enhance performance of digital contact tracing and should be considered in the currently developed mobile applications.
Many interesting problems in fields ranging from telecommunications to computational biology can be formalized in terms of large underdetermined systems of linear equations with additional constraints or regularizers. One of the most studied ones, th
e Compressed Sensing problem (CS), consists in finding the solution with the smallest number of non-zero components of a given system of linear equations $boldsymbol y = mathbf{F} boldsymbol{w}$ for known measurement vector $boldsymbol{y}$ and sensing matrix $mathbf{F}$. Here, we will address the compressed sensing problem within a Bayesian inference framework where the sparsity constraint is remapped into a singular prior distribution (called Spike-and-Slab or Bernoulli-Gauss). Solution to the problem is attempted through the computation of marginal distributions via Expectation Propagation (EP), an iterative computational scheme originally developed in Statistical Physics. We will show that this strategy is comparatively more accurate than the alternatives in solving instances of CS generated from statistically correlated measurement matrices. For computational strategies based on the Bayesian framework such as variants of Belief Propagation, this is to be expected, as they implicitly rely on the hypothesis of statistical independence among the entries of the sensing matrix. Perhaps surprisingly, the method outperforms uniformly also all the other state-of-the-art methods in our tests.
Computing marginal distributions of discrete or semidiscrete Markov random fields (MRFs) is a fundamental, generally intractable problem with a vast number of applications in virtually all fields of science. We present a new family of computational s
chemes to approximately calculate the marginals of discrete MRFs. This method shares some desirable properties with belief propagation, in particular, providing exact marginals on acyclic graphs, but it differs with the latter in that it includes some loop corrections; i.e., it takes into account correlations coming from all cycles in the factor graph. It is also similar to the adaptive Thouless-Anderson-Palmer method, but it differs with the latter in that the consistency is not on the first two moments of the distribution but rather on the value of its density on a subset of values. The results on finite-dimensional Isinglike models show a significant improvement with respect to the Bethe-Peierls (tree) approximation in all cases and with respect to the plaquette cluster variational method approximation in many cases. In particular, for the critical inverse temperature $beta_{c}$ of the homogeneous hypercubic lattice, the expansion of $left(dbeta_{c}right)^{-1}$ around $d=infty$ of the proposed scheme is exact up to the $d^{-4}$ order, whereas the two latter are exact only up to the $d^{-2}$ order.
We present a Bayesian approach for the Contamination Source Detection problem in Water Distribution Networks. Given an observation of contaminants in one or more nodes in the network, we try to give probable explanation for it assuming that contamina
tion is a rare event. We introduce extra variables to characterize the place and pattern of the first contamination event. Then we write down the posterior distribution for these extra variables given the observation obtained by the sensors. Our method relies on Belief Propagation for the evaluation of the marginals of this posterior distribution and the determination of the most likely origin. The method is implemented on a simplified binary forward-in-time dynamics. Simulations on data coming from the realistic simulation software EPANET on two networks show that the simplified model is nevertheless flexible enough to capture crucial information about contaminant sources.
We study the inference of the origin and the pattern of contamination in water distribution networks. We assume a simplified model for the dyanmics of the contamination spread inside a water distribution network, and assume that at some random locati
on a sensor detects the presence of contaminants. We transform the source location problem into an optimization problem by considering discrete times and a binary contaminated/not contaminated state for the nodes of the network. The resulting problem is solved by Mixed Integer Linear Programming. We test our results on random networks as well as in the Modena city network.
Assuming a steady-state condition within a cell, metabolic fluxes satisfy an under-determined linear system of stoichiometric equations. Characterizing the space of fluxes that satisfy such equations along with given bounds (and possibly additional r
elevant constraints) is considered of utmost importance for the understanding of cellular metabolism. Extreme values for each individual flux can be computed with Linear Programming (as Flux Balance Analysis), and their marginal distributions can be approximately computed with Monte-Carlo sampling. Here we present an approximate analytic method for the latter task based on Expectation Propagation equations that does not involve sampling and can achieve much better predictions than other existing analytic methods. The method is iterative, and its computation time is dominated by one matrix inversion per iteration. With respect to sampling, we show through extensive simulation that it has some advantages including computation time, and the ability to efficiently fix empirically estimated distributions of fluxes.
We study the network dismantling problem, which consists in determining a minimal set of vertices whose removal leaves the network broken into connected components of sub-extensive size. For a large class of random graphs, this problem is tightly con
nected to the decycling problem (the removal of vertices leaving the graph acyclic). Exploiting this connection and recent works on epidemic spreading we present precise predictions for the minimal size of a dismantling set in a large random graph with a prescribed (light-tailed) degree distribution. Building on the statistical mechanics perspective we propose a three-stage Min-Sum algorithm for efficiently dismantling networks, including heavy-tailed ones for which the dismantling and decycling problems are not equivalent. We also provide further insights into the dismantling problem concluding that it is an intrinsically collective problem and that optimal dismantling sets cannot be viewed as a collection of individually well performing nodes.
