Numerical algebraic geometry for model selection and its application to the life sciences

Researchers working with mathematical models are often confronted by the related problems of parameter estimation, model validation, and model selection. These are all optimization problems, well-known to be challenging due to non-linearity, non-convexity and multiple local optima. Furthermore, the challenges are compounded when only partial data is available. Here, we consider polynomial models (e.g., mass-action chemical reaction networks at steady state) and describe a framework for their analysis based on optimization using numerical algebraic geometry. Specifically, we use probability-one polynomial homotopy continuation methods to compute all critical points of the objective function, then filter to recover the global optima. Our approach exploits the geometric structures relating models and data, and we demonstrate its utility on examples from cell signaling, synthetic biology, and epidemiology.Comment: References added, additional clarification

A Maximum Entropy Procedure to Solve Likelihood Equations

In this article, we provide initial findings regarding the problem of solving likelihood equations by means of a maximum entropy (ME) approach. Unlike standard procedures that require equating the score function of the maximum likelihood problem at zero, we propose an alternative strategy where the score is instead used as an external informative constraint to the maximization of the convex Shannon\u2019s entropy function. The problem involves the reparameterization of the score parameters as expected values of discrete probability distributions where probabilities need to be estimated. This leads to a simpler situation where parameters are searched in smaller (hyper) simplex space. We assessed our proposal by means of empirical case studies and a simulation study, the latter involving the most critical case of logistic regression under data separation. The results suggested that the maximum entropy reformulation of the score problem solves the likelihood equation problem. Similarly, when maximum likelihood estimation is difficult, as is the case of logistic regression under separation, the maximum entropy proposal achieved results (numerically) comparable to those obtained by the Firth\u2019s bias-corrected approach. Overall, these first findings reveal that a maximum entropy solution can be considered as an alternative technique to solve the likelihood equation

Darwin's Rainbow: Evolutionary radiation and the spectrum of consciousness

Evolution is littered with paraphyletic convergences: many roads lead to functional Romes. We propose here another example - an equivalence class structure factoring the broad realm of possible realizations of the Baars Global Workspace consciousness model. The construction suggests many different physiological systems can support rapidly shifting, sometimes highly tunable, temporary assemblages of interacting unconscious cognitive modules. The discovery implies various animal taxa exhibiting behaviors we broadly recognize as conscious are, in fact, simply expressing different forms of the same underlying phenomenon. Mathematically, we find much slower, and even multiple simultaneous, versions of the basic structure can operate over very long timescales, a kind of paraconsciousness often ascribed to group phenomena. The variety of possibilities, a veritable rainbow, suggests minds today may be only a small surviving fraction of ancient evolutionary radiations - bush phylogenies of consciousness and paraconsciousness. Under this scenario, the resulting diversity was subsequently pruned by selection and chance extinction. Though few traces of the radiation may be found in the direct fossil record, exaptations and vestiges are scattered across the living mind. Humans, for instance, display an uncommonly profound synergism between individual consciousness and their embedding cultural heritages, enabling efficient Lamarkian adaptation

Nonparametric ridge estimation

We study the problem of estimating the ridges of a density function. Ridge estimation is an extension of mode finding and is useful for understanding the structure of a density. It can also be used to find hidden structure in point cloud data. We show that, under mild regularity conditions, the ridges of the kernel density estimator consistently estimate the ridges of the true density. When the data are noisy measurements of a manifold, we show that the ridges are close and topologically similar to the hidden manifold. To find the estimated ridges in practice, we adapt the modified mean-shift algorithm proposed by Ozertem and Erdogmus [J. Mach. Learn. Res. 12 (2011) 1249-1286]. Some numerical experiments verify that the algorithm is accurate.Comment: Published in at http://dx.doi.org/10.1214/14-AOS1218 the Annals of Statistics (http://www.imstat.org/aos/) by the Institute of Mathematical Statistics (http://www.imstat.org