Dataset Information

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

ABSTRACT: Understanding the basis for intracellular motion is critical as the field moves toward a deeper understanding of the relation between Brownian forces, molecular crowding, and anisotropic (or isotropic) energetic forcing. 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 discusses limitations in currently popular analysis methods (e.g., mean square displacement-based analyses) and how new techniques can be used to systematically analyze Single Particle Tracking (SPT) data experiencing abrupt state changes in time or space. The approach is to track GFP tagged chromatids in metaphase in live yeast cells and quantitatively probe the effective forces resulting from dynamic interactions that reflect the sum of a number of physical phenomena. State changes can be induced by various sources including: microtubule dynamics exerting force through the centromere, thermal polymer fluctuations, and DNA-based molecular machines including polymerases and protein exchange complexes such as chaperones and chromatin remodeling complexes. Simulations aiming to show the relevance of the approach to more general SPT data analyses are also studied. 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/or subjective information.

SUBMITTER: Calderon CP

PROVIDER: S-EPMC4575198 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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

Calderon Christopher P CP Bloom Kerry K

PloS one 20150918 9

Understanding the basis for intracellular motion is critical as the field moves toward a deeper understanding of the relation between Brownian forces, molecular crowding, and anisotropic (or isotropic) energetic forcing. 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 discusse ...[more]

PMID: 26384324

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Project description:Interactions between stressed organisms and their microbiome environments may provide new routes for understanding and controlling biological systems. However, microbiomes are a form of high-dimensional data, with thousands of taxa present in any given sample, which makes untangling the interaction between an organism and its microbial environment a challenge. Here we apply Latent Dirichlet Allocation (LDA), a technique for language modeling, which decomposes the microbial communities into a set of topics (non-mutually-exclusive sub-communities) that compactly represent the distribution of full communities. LDA provides a lens into the microbiome at broad and fine-grained taxonomic levels, which we show on two datasets. In the first dataset, from the literature, we show how LDA topics succinctly recapitulate many results from a previous study on diseased coral species. We then apply LDA to a new dataset of maize soil microbiomes under drought, and find a large number of significant associations between the microbiome topics and plant traits as well as associations between the microbiome and the experimental factors, e.g. watering level. This yields new information on the plant-microbial interactions in maize and shows that LDA technique is useful for studying the coupling between microbiomes and stressed organisms. Author summary Host-microbe interaction may be an important factor determining the performance and survival of an organism under stress. Understanding how microbiomes influence organisms under stress is a challenging new area of research because microbiomes are complex with the potential for complex responses and adaptations to stress that influence their interactions with the other stressed organisms. We show the use of LDA, a data-science technique in the context of environmental microbial datasets to break down the thousands of microbes present in samples into groups called topics; each topic is a group of organisms that occur together as a common pattern in the dataset. We show that this technique, combined with correlation analyses, provides a way to view a very large set of microbes in a sample as a smaller, more manageable set of communities of microbial taxa related to experimental conditions and plant traits. In this way, LDA helps to unravel complex interactions between organisms and their microbiome, which could help to better predict the behavior of real-world ecological systems, and perhaps support them through many challenges brought by changing climate and environment.

Dataset Information

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

Publications

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

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