A temporal switch model for estimating transcriptional activity in gene expression

Motivation: The analysis and mechanistic modelling of time series gene expression data provided by techniques such as microarrays, NanoString, reverse transcription–polymerase chain reaction and advanced sequencing are invaluable for developing an understanding of the variation in key biological processes. We address this by proposing the estimation of a flexible dynamic model, which decouples temporal synthesis and degradation of mRNA and, hence, allows for transcriptional activity to switch between different states. Results: The model is flexible enough to capture a variety of observed transcriptional dynamics, including oscillatory behaviour, in a way that is compatible with the demands imposed by the quality, time-resolution and quantity of the data. We show that the timing and number of switch events in transcriptional activity can be estimated alongside individual gene mRNA stability with the help of a Bayesian reversible jump Markov chain Monte Carlo algorithm. To demonstrate the methodology, we focus on modelling the wild-type behaviour of a selection of 200 circadian genes of the model plant Arabidopsis thaliana. The results support the idea that using a mechanistic model to identify transcriptional switch points is likely to strongly contribute to efforts in elucidating and understanding key biological processes, such as transcription and degradation

Clustering Time Series from Mixture Polynomial Models with Discretised Data

Clustering time series is an active research area with applications in many fields. One common feature of time series is the likely presence of outliers. These uncharacteristic data can significantly effect the quality of clusters formed. This paper evaluates a method of over-coming the detrimental effects of outliers. We describe some of the alternative approaches to clustering time series, then specify a particular class of model for experimentation with k-means clustering and a correlation based distance metric. For data derived from this class of model we demonstrate that discretising the data into a binary series of above and below the median improves the clustering when the data has outliers. More specifically, we show that firstly discretisation does not significantly effect the accuracy of the clusters when there are no outliers and secondly it significantly increases the accuracy in the presence of outliers, even when the probability of outlier is very low

The EM Algorithm and the Rise of Computational Biology

In the past decade computational biology has grown from a cottage industry with a handful of researchers to an attractive interdisciplinary field, catching the attention and imagination of many quantitatively-minded scientists. Of interest to us is the key role played by the EM algorithm during this transformation. We survey the use of the EM algorithm in a few important computational biology problems surrounding the "central dogma"; of molecular biology: from DNA to RNA and then to proteins. Topics of this article include sequence motif discovery, protein sequence alignment, population genetics, evolutionary models and mRNA expression microarray data analysis.Comment: Published in at http://dx.doi.org/10.1214/09-STS312 the Statistical Science (http://www.imstat.org/sts/) by the Institute of Mathematical Statistics (http://www.imstat.org

Graph Estimation From Multi-attribute Data

Many real world network problems often concern multivariate nodal attributes such as image, textual, and multi-view feature vectors on nodes, rather than simple univariate nodal attributes. The existing graph estimation methods built on Gaussian graphical models and covariance selection algorithms can not handle such data, neither can the theories developed around such methods be directly applied. In this paper, we propose a new principled framework for estimating graphs from multi-attribute data. Instead of estimating the partial correlation as in current literature, our method estimates the partial canonical correlations that naturally accommodate complex nodal features. Computationally, we provide an efficient algorithm which utilizes the multi-attribute structure. Theoretically, we provide sufficient conditions which guarantee consistent graph recovery. Extensive simulation studies demonstrate performance of our method under various conditions. Furthermore, we provide illustrative applications to uncovering gene regulatory networks from gene and protein profiles, and uncovering brain connectivity graph from functional magnetic resonance imaging data.Comment: Extended simulation study. Added an application to a new data se