45,622 research outputs found
Inferring causal relations from multivariate time series : a fast method for large-scale gene expression data
Various multivariate time series analysis techniques have been developed with the aim of inferring causal relations between time series. Previously, these techniques have proved their effectiveness on economic and neurophysiological data, which normally consist of hundreds of samples. However, in their applications to gene regulatory inference, the small sample size of gene expression time series poses an obstacle. In this paper, we describe some of the most commonly used multivariate inference techniques and show the potential challenge related to gene expression analysis. In response, we propose a directed partial correlation (DPC) algorithm as an efficient and effective solution to causal/regulatory relations inference on small sample gene expression data. Comparative evaluations on the existing techniques and the proposed method are presented. To draw reliable conclusions, a comprehensive benchmarking on data sets of various setups is essential. Three experiments are designed to assess these methods in a coherent manner. Detailed analysis of experimental results not only reveals good accuracy of the proposed DPC method in large-scale prediction, but also gives much insight into all methods under evaluation
A Bayesian approach for inferring neuronal connectivity from calcium fluorescent imaging data
Deducing the structure of neural circuits is one of the central problems of
modern neuroscience. Recently-introduced calcium fluorescent imaging methods
permit experimentalists to observe network activity in large populations of
neurons, but these techniques provide only indirect observations of neural
spike trains, with limited time resolution and signal quality. In this work we
present a Bayesian approach for inferring neural circuitry given this type of
imaging data. We model the network activity in terms of a collection of coupled
hidden Markov chains, with each chain corresponding to a single neuron in the
network and the coupling between the chains reflecting the network's
connectivity matrix. We derive a Monte Carlo Expectation--Maximization
algorithm for fitting the model parameters; to obtain the sufficient statistics
in a computationally-efficient manner, we introduce a specialized
blockwise-Gibbs algorithm for sampling from the joint activity of all observed
neurons given the observed fluorescence data. We perform large-scale
simulations of randomly connected neuronal networks with biophysically
realistic parameters and find that the proposed methods can accurately infer
the connectivity in these networks given reasonable experimental and
computational constraints. In addition, the estimation accuracy may be improved
significantly by incorporating prior knowledge about the sparseness of
connectivity in the network, via standard L penalization methods.Comment: Published in at http://dx.doi.org/10.1214/09-AOAS303 the Annals of
Applied Statistics (http://www.imstat.org/aoas/) by the Institute of
Mathematical Statistics (http://www.imstat.org
Efficient inference of parsimonious phenomenological models of cellular dynamics using S-systems and alternating regression
The nonlinearity of dynamics in systems biology makes it hard to infer them
from experimental data. Simple linear models are computationally efficient, but
cannot incorporate these important nonlinearities. An adaptive method based on
the S-system formalism, which is a sensible representation of nonlinear
mass-action kinetics typically found in cellular dynamics, maintains the
efficiency of linear regression. We combine this approach with adaptive model
selection to obtain efficient and parsimonious representations of cellular
dynamics. The approach is tested by inferring the dynamics of yeast glycolysis
from simulated data. With little computing time, it produces dynamical models
with high predictive power and with structural complexity adapted to the
difficulty of the inference problem.Comment: 14 pages, 2 figure
Fast non-negative deconvolution for spike train inference from population calcium imaging
Calcium imaging for observing spiking activity from large populations of
neurons are quickly gaining popularity. While the raw data are fluorescence
movies, the underlying spike trains are of interest. This work presents a fast
non-negative deconvolution filter to infer the approximately most likely spike
train for each neuron, given the fluorescence observations. This algorithm
outperforms optimal linear deconvolution (Wiener filtering) on both simulated
and biological data. The performance gains come from restricting the inferred
spike trains to be positive (using an interior-point method), unlike the Wiener
filter. The algorithm is fast enough that even when imaging over 100 neurons,
inference can be performed on the set of all observed traces faster than
real-time. Performing optimal spatial filtering on the images further refines
the estimates. Importantly, all the parameters required to perform the
inference can be estimated using only the fluorescence data, obviating the need
to perform joint electrophysiological and imaging calibration experiments.Comment: 22 pages, 10 figure
Structure Learning in Coupled Dynamical Systems and Dynamic Causal Modelling
Identifying a coupled dynamical system out of many plausible candidates, each
of which could serve as the underlying generator of some observed measurements,
is a profoundly ill posed problem that commonly arises when modelling real
world phenomena. In this review, we detail a set of statistical procedures for
inferring the structure of nonlinear coupled dynamical systems (structure
learning), which has proved useful in neuroscience research. A key focus here
is the comparison of competing models of (ie, hypotheses about) network
architectures and implicit coupling functions in terms of their Bayesian model
evidence. These methods are collectively referred to as dynamical casual
modelling (DCM). We focus on a relatively new approach that is proving
remarkably useful; namely, Bayesian model reduction (BMR), which enables rapid
evaluation and comparison of models that differ in their network architecture.
We illustrate the usefulness of these techniques through modelling
neurovascular coupling (cellular pathways linking neuronal and vascular
systems), whose function is an active focus of research in neurobiology and the
imaging of coupled neuronal systems
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