4,431 research outputs found
Computing the likelihood of sequence segmentation under Markov modelling
I tackle the problem of partitioning a sequence into homogeneous segments,
where homogeneity is defined by a set of Markov models. The problem is to study
the likelihood that a sequence is divided into a given number of segments.
Here, the moments of this likelihood are computed through an efficient
algorithm. Unlike methods involving Hidden Markov Models, this algorithm does
not require probability transitions between the models. Among many possible
usages of the likelihood, I present a maximum \textit{a posteriori} probability
criterion to predict the number of homogeneous segments into which a sequence
can be divided, and an application of this method to find CpG islands
Simplifying the mosaic description of DNA sequences
By using the Jensen-Shannon divergence, genomic DNA can be divided into
compositionally distinct domains through a standard recursive segmentation
procedure. Each domain, while significantly different from its neighbours, may
however share compositional similarity with one or more distant
(non--neighbouring) domains. We thus obtain a coarse--grained description of
the given DNA string in terms of a smaller set of distinct domain labels. This
yields a minimal domain description of a given DNA sequence, significantly
reducing its organizational complexity. This procedure gives a new means of
evaluating genomic complexity as one examines organisms ranging from bacteria
to human. The mosaic organization of DNA sequences could have originated from
the insertion of fragments of one genome (the parasite) inside another (the
host), and we present numerical experiments that are suggestive of this
scenario.Comment: 16 pages, 1 figure, Accepted for publication in Phys. Rev.
ModHMM: A Modular Supra-Bayesian Genome Segmentation Method
Genome segmentation methods are powerful tools to obtain cell type or tissue-specific genome-wide annotations and are frequently used to discover regulatory elements. However, traditional segmentation methods show low predictive accuracy and their data-driven annotations have some undesirable properties. As an alternative, we developed ModHMM, a highly modular genome segmentation method. Inspired by the supra-Bayesian approach, it incorporates predictions from a set of classifiers. This allows to compute genome segmentations by utilizing state-of-the-art methodology. We demonstrate the method on ENCODE data and show that it outperforms traditional segmentation methods not only in terms of predictive performance, but also in qualitative aspects. Therefore, ModHMM is a valuable alternative to study the epigenetic and regulatory landscape across and within cell types or tissues
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
A novel neural network approach to cDNA microarray image segmentation
This is the post-print version of the Article. The official published version can be accessed from the link below. Copyright @ 2013 Elsevier.Microarray technology has become a great source of information for biologists to understand the workings of DNA which is one of the most complex codes in nature. Microarray images typically contain several thousands of small spots, each of which represents a different gene in the experiment. One of the key steps in extracting information from a microarray image is the segmentation whose aim is to identify which pixels within an image represent which gene. This task is greatly complicated by noise within the image and a wide degree of variation in the values of the pixels belonging to a typical spot. In the past there have been many methods proposed for the segmentation of microarray image. In this paper, a new method utilizing a series of artificial neural networks, which are based on multi-layer perceptron (MLP) and Kohonen networks, is proposed. The proposed method is applied to a set of real-world cDNA images. Quantitative comparisons between the proposed method and commercial software GenePix(®) are carried out in terms of the peak signal-to-noise ratio (PSNR). This method is shown to not only deliver results comparable and even superior to existing techniques but also have a faster run time.This work was funded in part by the National Natural Science Foundation of China under Grants 61174136 and 61104041, the Natural Science Foundation of Jiangsu Province of China under Grant BK2011598, the International Science and Technology Cooperation Project of China under Grant No. 2011DFA12910, the Engineering and Physical Sciences Research Council (EPSRC) of the U.K. under Grant GR/S27658/01, the Royal Society of the U.K., and the Alexander von Humboldt Foundation of Germany
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