10,747 research outputs found
Patterns of subnet usage reveal distinct scales of regulation in the transcriptional regulatory network of Escherichia coli
The set of regulatory interactions between genes, mediated by transcription
factors, forms a species' transcriptional regulatory network (TRN). By
comparing this network with measured gene expression data one can identify
functional properties of the TRN and gain general insight into transcriptional
control. We define the subnet of a node as the subgraph consisting of all nodes
topologically downstream of the node, including itself. Using a large set of
microarray expression data of the bacterium Escherichia coli, we find that the
gene expression in different subnets exhibits a structured pattern in response
to environmental changes and genotypic mutation. Subnets with less changes in
their expression pattern have a higher fraction of feed-forward loop motifs and
a lower fraction of small RNA targets within them. Our study implies that the
TRN consists of several scales of regulatory organization: 1) subnets with more
varying gene expression controlled by both transcription factors and
post-transcriptional RNA regulation, and 2) subnets with less varying gene
expression having more feed-forward loops and less post-transcriptional RNA
regulation.Comment: 14 pages, 8 figures, to be published in PLoS Computational Biolog
An introduction to Graph Data Management
A graph database is a database where the data structures for the schema
and/or instances are modeled as a (labeled)(directed) graph or generalizations
of it, and where querying is expressed by graph-oriented operations and type
constructors. In this article we present the basic notions of graph databases,
give an historical overview of its main development, and study the main current
systems that implement them
Practical Bayesian Optimization of Machine Learning Algorithms
Machine learning algorithms frequently require careful tuning of model
hyperparameters, regularization terms, and optimization parameters.
Unfortunately, this tuning is often a "black art" that requires expert
experience, unwritten rules of thumb, or sometimes brute-force search. Much
more appealing is the idea of developing automatic approaches which can
optimize the performance of a given learning algorithm to the task at hand. In
this work, we consider the automatic tuning problem within the framework of
Bayesian optimization, in which a learning algorithm's generalization
performance is modeled as a sample from a Gaussian process (GP). The tractable
posterior distribution induced by the GP leads to efficient use of the
information gathered by previous experiments, enabling optimal choices about
what parameters to try next. Here we show how the effects of the Gaussian
process prior and the associated inference procedure can have a large impact on
the success or failure of Bayesian optimization. We show that thoughtful
choices can lead to results that exceed expert-level performance in tuning
machine learning algorithms. We also describe new algorithms that take into
account the variable cost (duration) of learning experiments and that can
leverage the presence of multiple cores for parallel experimentation. We show
that these proposed algorithms improve on previous automatic procedures and can
reach or surpass human expert-level optimization on a diverse set of
contemporary algorithms including latent Dirichlet allocation, structured SVMs
and convolutional neural networks
Multiple instance learning for sequence data with across bag dependencies
In Multiple Instance Learning (MIL) problem for sequence data, the instances
inside the bags are sequences. In some real world applications such as
bioinformatics, comparing a random couple of sequences makes no sense. In fact,
each instance may have structural and/or functional relations with instances of
other bags. Thus, the classification task should take into account this across
bag relation. In this work, we present two novel MIL approaches for sequence
data classification named ABClass and ABSim. ABClass extracts motifs from
related instances and use them to encode sequences. A discriminative classifier
is then applied to compute a partial classification result for each set of
related sequences. ABSim uses a similarity measure to discriminate the related
instances and to compute a scores matrix. For both approaches, an aggregation
method is applied in order to generate the final classification result. We
applied both approaches to solve the problem of bacterial Ionizing Radiation
Resistance prediction. The experimental results of the presented approaches are
satisfactory
Ranking and significance of variable-length similarity-based time series motifs
The detection of very similar patterns in a time series, commonly called
motifs, has received continuous and increasing attention from diverse
scientific communities. In particular, recent approaches for discovering
similar motifs of different lengths have been proposed. In this work, we show
that such variable-length similarity-based motifs cannot be directly compared,
and hence ranked, by their normalized dissimilarities. Specifically, we find
that length-normalized motif dissimilarities still have intrinsic dependencies
on the motif length, and that lowest dissimilarities are particularly affected
by this dependency. Moreover, we find that such dependencies are generally
non-linear and change with the considered data set and dissimilarity measure.
Based on these findings, we propose a solution to rank those motifs and measure
their significance. This solution relies on a compact but accurate model of the
dissimilarity space, using a beta distribution with three parameters that
depend on the motif length in a non-linear way. We believe the incomparability
of variable-length dissimilarities could go beyond the field of time series,
and that similar modeling strategies as the one used here could be of help in a
more broad context.Comment: 20 pages, 10 figure
Validating module network learning algorithms using simulated data
In recent years, several authors have used probabilistic graphical models to
learn expression modules and their regulatory programs from gene expression
data. Here, we demonstrate the use of the synthetic data generator SynTReN for
the purpose of testing and comparing module network learning algorithms. We
introduce a software package for learning module networks, called LeMoNe, which
incorporates a novel strategy for learning regulatory programs. Novelties
include the use of a bottom-up Bayesian hierarchical clustering to construct
the regulatory programs, and the use of a conditional entropy measure to assign
regulators to the regulation program nodes. Using SynTReN data, we test the
performance of LeMoNe in a completely controlled situation and assess the
effect of the methodological changes we made with respect to an existing
software package, namely Genomica. Additionally, we assess the effect of
various parameters, such as the size of the data set and the amount of noise,
on the inference performance. Overall, application of Genomica and LeMoNe to
simulated data sets gave comparable results. However, LeMoNe offers some
advantages, one of them being that the learning process is considerably faster
for larger data sets. Additionally, we show that the location of the regulators
in the LeMoNe regulation programs and their conditional entropy may be used to
prioritize regulators for functional validation, and that the combination of
the bottom-up clustering strategy with the conditional entropy-based assignment
of regulators improves the handling of missing or hidden regulators.Comment: 13 pages, 6 figures + 2 pages, 2 figures supplementary informatio
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