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Biology subjects

Aravkin, A.

Publications and source records attributed to Aravkin, A..

4 recordsLinked to original sources

WENDY: Gene Regulatory Network Inference with Covariance Dynamics

Determining gene regulatory network (GRN) structure is a central problem in biology, with a variety of inference methods available for different types of data. For a widely prevalent and challenging use case, namely single-cell gene expression data measured after intervention at multiple time points with unknown joint distributions, there is only one known specifically developed method, which does not fully utilize the rich information contained in this data type. We develop an inference method for the GRN in this case, netWork infErence by covariaNce DYnamics, dubbed WENDY. The core idea of WENDY is to model the dynamics of the covariance matrix, and solve this dynamics as an optimization problem to determine the regulatory relationships. To evaluate its effectiveness, we compare WENDY with other inference methods using synthetic data and experimental data. Our results demonstrate that WENDY performs well across different data sets.

genetics↗

Trimmed Constrained Mixed Effects Models: Formulations and Algorithms.

Mixed effects (ME) models inform a vast array of problems in the physical and social sciences, and are pervasive in meta-analysis. We consider ME models where the random effects component is linear. We then develop an efficient approach for a broad problem class that allows nonlinear measurements, priors, and constraints, and finds robust estimates in all of these cases using trimming in the associated marginal likelihood. The software accompanying this paper is disseminated as an open-source Python package called LimeTr. LimeTr is able to recover results more accurately in the presence of outliers compared to available packages for both standard longitudinal analysis and meta-analysis, and is also more computationally efficient than competing robust alternatives. Supplementary materials that reproduce the simulations, as well as run LimeTr and third party code are available online. We also present analyses of global health data, where we use advanced functionality of LimeTr, including constraints to impose monotonicity and concavity for dose-response relationships. Nonlinear observation models allow new analyses in place of classic approximations, such as log-linear models. Robust extensions in all analyses ensure that spurious data points do not drive our understanding of either mean relationships or between-study heterogeneity.

bioinformatics↗

Computer Assisted Localization of a Heart Arrhythmia

We consider the problem of locating a point-source heart arrhythmia using data from a standard diagnostic procedure, where a reference catheter is placed in the heart, and arrival times from a second diagnostic catheter are recorded as the diagnostic catheter moves around within the heart.\n\nWe model this situation as a nonconvex feasibility problem, where given a set of arrival times, we look for a source location that is consistent with the available data. We develop a new optimization approach and fast algorithm to obtain online proposals for the next location to suggest to the operator as she collects data. We validate the procedure using a Monte Carlo simulation based on patients electrophysiological data. The proposed procedure robustly and quickly locates the source of arrhythmias without any prior knowledge of heart anatomy.

bioengineering↗

Learning Nonlinear Brain Dynamics: van der Pol Meets LSTM

Many real-world data sets, especially in biology, are produced by highly multivariate and nonlinear complex dynamical systems. In this paper, we focus on brain imaging data, including both calcium imaging and functional MRI data. Standard vector-autoregressive models are limited by their linearity assumptions, while nonlinear general-purpose, large-scale temporal models, such as LSTM networks, typically require large amounts of training data, not always readily available in biological applications; furthermore, such models have limited interpretability. We introduce here a novel approach for learning a nonlinear differential equation model aimed at capturing brain dynamics. Specifically, we propose a variable-projection optimization approach to estimate the parameters of the multivariate (coupled) van der Pol oscillator, and demonstrate that such a model can accurately represent nonlinear dynamics of the brain data. Furthermore, in order to improve the predictive accuracy when forecasting future brain-activity time series, we use this analytical model as an unlimited source of simulated data for pretraining LSTM; such model-specific data augmentation approach consistently improves LSTM performance on both calcium and fMRI imaging data.

neuroscience↗