De Novo Antimicrobial Peptide Design with Feedback Generative Adversarial Networks.

Antimicrobial peptides (AMPs) are promising candidates for new antibiotics due to their broad-spectrum activity against pathogens and reduced susceptibility to resistance development. Deep-learning techniques, such as deep generative models, offer a promising avenue to expedite the discovery and optimization of AMPs. A remarkable example is the Feedback Generative Adversarial Network (FBGAN), a deep generative model that incorporates a classifier during its training phase.

Learning biologically-interpretable latent representations for gene expression data: Pathway Activity Score Learning Algorithm.

Molecular gene-expression datasets consist of samples with tens of thousands of measured quantities (i.e., high dimensional data).

Cumulant GAN.

In this article, we propose a novel loss function for training generative adversarial networks (GANs) aiming toward deeper theoretical understanding as well as improved stability and performance for the underlying optimization problem. The new loss function is based on cumulant generating functions (CGFs) giving rise to Cumulant GAN. Relying on a recently derived variational formula, we show that the corresponding optimization problem is equivalent to Rényi divergence minimization, thus offering a (partially) unified perspective of GAN losses: the Rényi family encompasses Kullback-Leibler divergence (KLD), reverse KLD, Hellinger distance, and χ -divergence.

A unified approach for sparse dynamical system inference from temporal measurements.

Motivation: Temporal variations in biological systems and more generally in natural sciences are typically modeled as a set of ordinary, partial or stochastic differential or difference equations. Algorithms for learning the structure and the parameters of a dynamical system are distinguished based on whether time is discrete or continuous, observations are time-series or time-course and whether the system is deterministic or stochastic, however, there is no approach able to handle the various types of dynamical systems simultaneously.

Results: In this paper, we present a unified approach to infer both the structure and the parameters of non-linear dynamical systems of any type under the restriction of being linear with respect to the unknown parameters.

Summary results of the 2014-2015 DARPA Chikungunya challenge.

Background: Emerging pathogens such as Zika, chikungunya, Ebola, and dengue viruses are serious threats to national and global health security. Accurate forecasts of emerging epidemics and their severity are critical to minimizing subsequent mortality, morbidity, and economic loss. The recent introduction of chikungunya and Zika virus to the Americas underscores the need for better methods for disease surveillance and forecasting.

Accelerated Sensitivity Analysis in High-Dimensional Stochastic Reaction Networks.

Existing sensitivity analysis approaches are not able to handle efficiently stochastic reaction networks with a large number of parameters and species, which are typical in the modeling and simulation of complex biochemical phenomena. In this paper, a two-step strategy for parametric sensitivity analysis for such systems is proposed, exploiting advantages and synergies between two recently proposed sensitivity analysis methodologies for stochastic dynamics. The first method performs sensitivity analysis of the stochastic dynamics by means of the Fisher Information Matrix on the underlying distribution of the trajectories; the second method is a reduced-variance, finite-difference, gradient-type sensitivity approach relying on stochastic coupling techniques for variance reduction.

Parametric sensitivity analysis for stochastic molecular systems using information theoretic metrics.

In this paper, we present a parametric sensitivity analysis (SA) methodology for continuous time and continuous space Markov processes represented by stochastic differential equations. Particularly, we focus on stochastic molecular dynamics as described by the Langevin equation. The utilized SA method is based on the computation of the information-theoretic (and thermodynamic) quantity of relative entropy rate (RER) and the associated Fisher information matrix (FIM) between path distributions, and it is an extension of the work proposed by Y.

Parametric sensitivity analysis for biochemical reaction networks based on pathwise information theory.

Background: Stochastic modeling and simulation provide powerful predictive methods for the intrinsic understanding of fundamental mechanisms in complex biochemical networks. Typically, such mathematical models involve networks of coupled jump stochastic processes with a large number of parameters that need to be suitably calibrated against experimental data. In this direction, the parameter sensitivity analysis of reaction networks is an essential mathematical and computational tool, yielding information regarding the robustness and the identifiability of model parameters.

A relative entropy rate method for path space sensitivity analysis of stationary complex stochastic dynamics.

We propose a new sensitivity analysis methodology for complex stochastic dynamics based on the relative entropy rate. The method becomes computationally feasible at the stationary regime of the process and involves the calculation of suitable observables in path space for the relative entropy rate and the corresponding Fisher information matrix. The stationary regime is crucial for stochastic dynamics and here allows us to address the sensitivity analysis of complex systems, including examples of processes with complex landscapes that exhibit metastability, non-reversible systems from a statistical mechanics perspective, and high-dimensional, spatially distributed models.