Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Increasing the Time Resolution of Single-Molecule Experiments with Bayesian Inference.

ABSTRACT: Many time-resolved single-molecule biophysics experiments seek to characterize the kinetics of biomolecular systems exhibiting dynamics that challenge the time resolution of the given technique. Here, we present a general, computational approach to this problem that employs Bayesian inference to learn the underlying dynamics of such systems, even when they are much faster than the time resolution of the experimental technique being used. By accurately and precisely inferring rate constants, our Bayesian inference for the analysis of subtemporal resolution dynamics approach effectively enables the experimenter to super-resolve the poorly resolved dynamics that are present in their data.

SUBMITTER: Kinz-Thompson CD

PROVIDER: S-EPMC5984981 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Increasing the Time Resolution of Single-Molecule Experiments with Bayesian Inference.

Kinz-Thompson Colin D CD Gonzalez Ruben L RL

Biophysical journal 20180101 2

Many time-resolved single-molecule biophysics experiments seek to characterize the kinetics of biomolecular systems exhibiting dynamics that challenge the time resolution of the given technique. Here, we present a general, computational approach to this problem that employs Bayesian inference to learn the underlying dynamics of such systems, even when they are much faster than the time resolution of the experimental technique being used. By accurately and precisely inferring rate constants, our ...[more]

PMID: 29401427

Similar Datasets

Bayesian Inference: The Comprehensive Approach to Analyzing Single-Molecule Experiments.

Project description:Biophysics experiments performed at single-molecule resolution provide exceptional insight into the structural details and dynamic behavior of biological systems. However, extracting this information from the corresponding experimental data unequivocally requires applying a biophysical model. In this review, we discuss how to use probability theory to apply these models to single-molecule data. Many current single-molecule data analysis methods apply parts of probability theory, sometimes unknowingly, and thus miss out on the full set of benefits provided by this self-consistent framework. The full application of probability theory involves a process called Bayesian inference that fully accounts for the uncertainties inherent to single-molecule experiments. Additionally, using Bayesian inference provides a scientifically rigorous method of incorporating information from multiple experiments into a single analysis and finding the best biophysical model for an experiment without the risk of overfitting the data. These benefits make the Bayesian approach ideal for analyzing any type of single-molecule experiment.

| S-EPMC8238404 | biostudies-literature

Analyzing single-molecule time series via nonparametric Bayesian inference.

Project description:The ability to measure the properties of proteins at the single-molecule level offers an unparalleled glimpse into biological systems at the molecular scale. The interpretation of single-molecule time series has often been rooted in statistical mechanics and the theory of Markov processes. While existing analysis methods have been useful, they are not without significant limitations including problems of model selection and parameter nonidentifiability. To address these challenges, we introduce the use of nonparametric Bayesian inference for the analysis of single-molecule time series. These methods provide a flexible way to extract structure from data instead of assuming models beforehand. We demonstrate these methods with applications to several diverse settings in single-molecule biophysics. This approach provides a well-constrained and rigorously grounded method for determining the number of biophysical states underlying single-molecule data.

| S-EPMC4317543 | biostudies-literature

Bayesian inference for improved single molecule fluorescence tracking.

Project description:Single molecule tracking is widely used to monitor the change in position of lipids and proteins in living cells. In many experiments in which molecules are tagged with a single or small number of fluorophores, the signal/noise ratio may be limiting, the number of molecules is not known, and fluorophore blinking and photobleaching can occur. All these factors make accurate tracking over long trajectories difficult and hence there is still a pressing need to develop better algorithms to extract the maximum information from a sequence of fluorescence images. We describe here a Bayesian-based inference approach, based on a trans-dimensional sequential Monte Carlo method that utilizes both the spatial and temporal information present in the image sequences. We show, using model data, where the real trajectory of the molecule is known, that our method allows accurate tracking of molecules over long trajectories even with low signal/noise ratio and in the presence of fluorescence blinking and photobleaching. The method is then applied to real experimental data.

| S-EPMC2397372 | biostudies-literature

Denoising single-molecule FRET trajectories with wavelets and Bayesian inference.

Project description:A method to denoise single-molecule fluorescence resonance energy (smFRET) trajectories using wavelet detail thresholding and Bayesian inference is presented. Bayesian methods are developed to identify fluorophore photoblinks in the time trajectories. Simulated data are used to quantify the improvement in static and dynamic data analysis. Application of the method to experimental smFRET data shows that it distinguishes photoblinks from large shifts in smFRET efficiency while maintaining the important advantage of an unbiased approach. Known sources of experimental noise are examined and quantified as a means to remove their contributions via soft thresholding of wavelet coefficients. A wavelet decomposition algorithm is described, and thresholds are produced through the knowledge of noise parameters in the discrete-time photon signals. Reconstruction of the signals from thresholded coefficients produces signals that contain noise arising only from unquantifiable parameters. The method is applied to simulated and observed smFRET data, and it is found that the denoised data retain their underlying dynamic properties, but with increased resolution.

| S-EPMC2800976 | biostudies-literature

Live cell single molecule-guided Bayesian localization super resolution microscopy.

Project description: Not available

| S-EPMC5520847 | biostudies-literature

NOBIAS: Analyzing anomalous diffusion in single-molecule tracks with nonparametric Bayesian inference.

Project description:Single particle tracking (SPT) enables the investigation of biomolecular dynamics at a high temporal and spatial resolution in living cells, and the analysis of these SPT datasets can reveal biochemical interactions and mechanisms. Still, how to make the best use of these tracking data for a broad set of experimental conditions remains an analysis challenge in the field. Here, we develop a new SPT analysis framework: NOBIAS (NOnparametric Bayesian Inference for Anomalous Diffusion in Single-Molecule Tracking), which applies nonparametric Bayesian statistics and deep learning approaches to thoroughly analyze SPT datasets. In particular, NOBIAS handles complicated live-cell SPT data for which: the number of diffusive states is unknown, mixtures of different diffusive populations may exist within single trajectories, symmetry cannot be assumed between the x and y directions, and anomalous diffusion is possible. NOBIAS provides the number of diffusive states without manual supervision, it quantifies the dynamics and relative populations of each diffusive state, it provides the transition probabilities between states, and it assesses the anomalous diffusion behavior for each state. We validate the performance of NOBIAS with simulated datasets and apply it to the diffusion of single outer-membrane proteins in Bacteroides thetaiotaomicron. Furthermore, we compare NOBIAS with other SPT analysis methods and find that, in addition to these advantages, NOBIAS is robust and has high computational efficiency and is particularly advantageous due to its ability to treat experimental trajectories with asymmetry and anomalous diffusion.

| S-EPMC9053523 | biostudies-literature

BayFish: Bayesian inference of transcription dynamics from population snapshots of single-molecule RNA FISH in single cells.

Project description:Single-molecule RNA fluorescence in situ hybridization (smFISH) provides unparalleled resolution in the measurement of the abundance and localization of nascent and mature RNA transcripts in fixed, single cells. We developed a computational pipeline (BayFish) to infer the kinetic parameters of gene expression from smFISH data at multiple time points after gene induction. Given an underlying model of gene expression, BayFish uses a Monte Carlo method to estimate the Bayesian posterior probability of the model parameters and quantify the parameter uncertainty given the observed smFISH data. We tested BayFish on synthetic data and smFISH measurements of the neuronal activity-inducible gene Npas4 in primary neurons.

| S-EPMC5582403 | biostudies-other

Bayesian inference of epidemiological parameters from transmission experiments.

Project description:Epidemiological parameters for livestock diseases are often inferred from transmission experiments. However, there are several limitations inherent to the design of such experiments that limits the precision of parameter estimates. In particular, infection times and latent periods cannot be directly observed and infectious periods may also be censored. We present a Bayesian framework accounting for these features directly and employ Markov chain Monte Carlo techniques to provide robust inferences and quantify the uncertainty in our estimates. We describe the transmission dynamics using a susceptible-exposed-infectious-removed compartmental model, with gamma-distributed transition times. We then fit the model to published data from transmission experiments for foot-and-mouth disease virus (FMDV) and African swine fever virus (ASFV). Where the previous analyses of these data made various assumptions on the unobserved processes in order to draw inferences, our Bayesian approach includes the unobserved infection times and latent periods and quantifies them along with all other model parameters. Drawing inferences about infection times helps identify who infected whom and can also provide insights into transmission mechanisms. Furthermore, we are able to use our models to measure the difference between the latent periods of inoculated and contact-challenged animals and to quantify the effect vaccination has on transmission.

| S-EPMC5711876 | biostudies-literature

A Bayesian inference scheme to extract diffusivity and potential fields from confined single-molecule trajectories.

Project description:Currently used techniques for the analysis of single-molecule trajectories only exploit a small part of the available information stored in the data. Here, we apply a Bayesian inference scheme to trajectories of confined receptors that are targeted by pore-forming toxins to extract the two-dimensional confining potential that restricts the motion of the receptor. The receptor motion is modeled by the overdamped Langevin equation of motion. The method uses most of the information stored in the trajectory and converges quickly onto inferred values, while providing the uncertainty on the determined values. The inference is performed on the polynomial development of the potential and on the diffusivities that have been discretized on a mesh. Numerical simulations are used to test the scheme and quantify the convergence toward the input values for forces, potential, and diffusivity. Furthermore, we show that the technique outperforms the classical mean-square-displacement technique when forces act on confined molecules because the typical mean-square-displacement analysis does not account for them. We also show that the inferred potential better represents input potentials than the potential extracted from the position distribution based on Boltzmann statistics that assumes statistical equilibrium.

| S-EPMC3353014 | biostudies-literature

Project description:Single-molecule-localization-microscopy (SMLM) enables superresolution imaging of biological samples down to ~ 10-20 nm and in single molecule detail. However, common SMLM reconstruction largely disregards information embedded in the entire intensity trajectories of individual emitters. Here, we develop and demonstrate an approach, termed time-correlated-SMLM (tcSMLM), that uses such information for enhancing SMLM reconstruction. Specifically, tcSMLM is shown to increase the spatial resolution and fidelity of SMLM reconstruction of both simulated and experimental data; esp. upon acquisition under stringent conditions of low SNR, high acquisition rate and high density of emitters. We further provide detailed guidelines and optimization procedures for effectively applying tcSMLM to data of choice. Importantly, our approach can be readily added in tandem to multiple SMLM and related superresolution reconstruction algorithms. Thus, we expect that our approach will become an effective and readily accessible tool for enhancing SMLM and superresolution imaging.

| S-EPMC7529757 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data