Inferring Latent States and Refining Force Estimates via Hierarchical Dirichlet Process Modeling in Single Particle Tracking Experiments

Optical microscopy provides rich spatio-temporal information characterizing in vivo molecular motion. However, effective forces and other parameters used to summarize molecular motion change over time in live cells due to latent state changes, e.g., changes induced by dynamic micro-environments, photobleaching, and other heterogeneity inherent in biological processes. This study focuses on techniques for analyzing Single Particle Tracking (SPT) data experiencing abrupt state changes. We demonstrate the approach on GFP tagged chromatids experiencing metaphase in yeast cells and probe the effective forces resulting from dynamic interactions that reflect the sum of a number of physical phenomena. State changes are induced by factors such as microtubule dynamics exerting force through the centromere, thermal polymer fluctuations, etc. Simulations are used to demonstrate the relevance of the approach in more general SPT data analyses. Refined force estimates are obtained by adopting and modifying a nonparametric Bayesian modeling technique, the Hierarchical Dirichlet Process Switching Linear Dynamical System (HDP-SLDS), for SPT applications. The HDP-SLDS method shows promise in systematically identifying dynamical regime changes induced by unobserved state changes when the number of underlying states is unknown in advance (a common problem in SPT applications). We expand on the relevance of the HDP-SLDS approach, review the relevant background of Hierarchical Dirichlet Processes, show how to map discrete time HDP-SLDS models to classic SPT models, and discuss limitations of the approach. In addition, we demonstrate new computational techniques for tuning hyperparameters and for checking the statistical consistency of model assumptions directly against individual experimental trajectories; the techniques circumvent the need for "ground-truth" and subjective information.Comment: 25 pages, 6 figures. Differs only typographically from PLoS One publication available freely as an open-access article at http://journals.plos.org/plosone/article?id=10.1371/journal.pone.013763

Experimental and computational analyses reveal that environmental restrictions shape HIV-1 spread in 3D cultures

Here, using an integrative experimental and computational approach, Imle et al. show how cell motility and density affect HIV cell-associated transmission in a three-dimensional tissue-like culture system of CD4+ T cells and collagen, and how different collagen matrices restrict infection by cell-free virions

PPF - A Parallel Particle Filtering Library

We present the parallel particle filtering (PPF) software library, which enables hybrid shared-memory/distributed-memory parallelization of particle filtering (PF) algorithms combining the Message Passing Interface (MPI) with multithreading for multi-level parallelism. The library is implemented in Java and relies on OpenMPI's Java bindings for inter-process communication. It includes dynamic load balancing, multi-thread balancing, and several algorithmic improvements for PF, such as input-space domain decomposition. The PPF library hides the difficulties of efficient parallel programming of PF algorithms and provides application developers with the necessary tools for parallel implementation of PF methods. We demonstrate the capabilities of the PPF library using two distributed PF algorithms in two scenarios with different numbers of particles. The PPF library runs a 38 million particle problem, corresponding to more than 1.86 GB of particle data, on 192 cores with 67% parallel efficiency. To the best of our knowledge, the PPF library is the first open-source software that offers a parallel framework for PF applications.Comment: 8 pages, 8 figures; will appear in the proceedings of the IET Data Fusion & Target Tracking Conference 201

Unraveling the Thousand Word Picture: An Introduction to Super-Resolution Data Analysis

Super-resolution microscopy provides direct insight into fundamental biological processes occurring at length scales smaller than light’s diffraction limit. The analysis of data at such scales has brought statistical and machine learning methods into the mainstream. Here we provide a survey of data analysis methods starting from an overview of basic statistical techniques underlying the analysis of super-resolution and, more broadly, imaging data. We subsequently break down the analysis of super-resolution data into four problems: the localization problem, the counting problem, the linking problem, and what we’ve termed the interpretation problem

Sparse approximations of protein structure from noisy random projections

Single-particle electron microscopy is a modern technique that biophysicists employ to learn the structure of proteins. It yields data that consist of noisy random projections of the protein structure in random directions, with the added complication that the projection angles cannot be observed. In order to reconstruct a three-dimensional model, the projection directions need to be estimated by use of an ad-hoc starting estimate of the unknown particle. In this paper we propose a methodology that does not rely on knowledge of the projection angles, to construct an objective data-dependent low-resolution approximation of the unknown structure that can serve as such a starting estimate. The approach assumes that the protein admits a suitable sparse representation, and employs discrete $L^1$-regularization (LASSO) as well as notions from shape theory to tackle the peculiar challenges involved in the associated inverse problem. We illustrate the approach by application to the reconstruction of an E. coli protein component called the Klenow fragment.Comment: Published in at http://dx.doi.org/10.1214/11-AOAS479 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org