14,864 research outputs found
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
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
Optimal Kullback-Leibler Aggregation via Information Bottleneck
In this paper, we present a method for reducing a regular, discrete-time
Markov chain (DTMC) to another DTMC with a given, typically much smaller number
of states. The cost of reduction is defined as the Kullback-Leibler divergence
rate between a projection of the original process through a partition function
and a DTMC on the correspondingly partitioned state space. Finding the reduced
model with minimal cost is computationally expensive, as it requires an
exhaustive search among all state space partitions, and an exact evaluation of
the reduction cost for each candidate partition. Our approach deals with the
latter problem by minimizing an upper bound on the reduction cost instead of
minimizing the exact cost; The proposed upper bound is easy to compute and it
is tight if the original chain is lumpable with respect to the partition. Then,
we express the problem in the form of information bottleneck optimization, and
propose using the agglomerative information bottleneck algorithm for searching
a sub-optimal partition greedily, rather than exhaustively. The theory is
illustrated with examples and one application scenario in the context of
modeling bio-molecular interactions.Comment: 13 pages, 4 figure
Detection of regulator genes and eQTLs in gene networks
Genetic differences between individuals associated to quantitative phenotypic
traits, including disease states, are usually found in non-coding genomic
regions. These genetic variants are often also associated to differences in
expression levels of nearby genes (they are "expression quantitative trait
loci" or eQTLs for short) and presumably play a gene regulatory role, affecting
the status of molecular networks of interacting genes, proteins and
metabolites. Computational systems biology approaches to reconstruct causal
gene networks from large-scale omics data have therefore become essential to
understand the structure of networks controlled by eQTLs together with other
regulatory genes, and to generate detailed hypotheses about the molecular
mechanisms that lead from genotype to phenotype. Here we review the main
analytical methods and softwares to identify eQTLs and their associated genes,
to reconstruct co-expression networks and modules, to reconstruct causal
Bayesian gene and module networks, and to validate predicted networks in
silico.Comment: minor revision with typos corrected; review article; 24 pages, 2
figure
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