4,252 research outputs found
Application of regulatory sequence analysis and metabolic network analysis to the interpretation of gene expression data
We present two complementary approaches for the interpretation of clusters of
co-regulated genes, such as those obtained from DNA chips and related methods.
Starting from a cluster of genes with similar expression profiles, two basic
questions can be asked:
1. Which mechanism is responsible for the coordinated transcriptional response
of the genes? This question is approached by extracting motifs that are shared
between the upstream sequences of these genes. The motifs extracted are putative
cis-acting regulatory elements.
2. What is the physiological meaning for the cell to express together these
genes? One way to answer the question is to search for potential metabolic
pathways that could be catalyzed by the products of the genes. This can be
done by selecting the genes from the cluster that code for enzymes, and trying
to assemble the catalyzed reactions to form metabolic pathways.
We present tools to answer these two questions, and we illustrate their use with
selected examples in the yeast Saccharomyces cerevisiae. The tools are available
on the web (http://ucmb.ulb.ac.be/bioinformatics/rsa-tools/;
http://www.ebi.ac.uk/research/pfbp/; http://www.soi.city.ac.uk/~msch/)
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A global transcriptional network connecting noncoding mutations to changes in tumor gene expression.
Although cancer genomes are replete with noncoding mutations, the effects of these mutations remain poorly characterized. Here we perform an integrative analysis of 930 tumor whole genomes and matched transcriptomes, identifying a network of 193 noncoding loci in which mutations disrupt target gene expression. These 'somatic eQTLs' (expression quantitative trait loci) are frequently mutated in specific cancer tissues, and the majority can be validated in an independent cohort of 3,382 tumors. Among these, we find that the effects of noncoding mutations on DAAM1, MTG2 and HYI transcription are recapitulated in multiple cancer cell lines and that increasing DAAM1 expression leads to invasive cell migration. Collectively, the noncoding loci converge on a set of core pathways, permitting a classification of tumors into pathway-based subtypes. The somatic eQTL network is disrupted in 88% of tumors, suggesting widespread impact of noncoding mutations in cancer
Temporal Networks
A great variety of systems in nature, society and technology -- from the web
of sexual contacts to the Internet, from the nervous system to power grids --
can be modeled as graphs of vertices coupled by edges. The network structure,
describing how the graph is wired, helps us understand, predict and optimize
the behavior of dynamical systems. In many cases, however, the edges are not
continuously active. As an example, in networks of communication via email,
text messages, or phone calls, edges represent sequences of instantaneous or
practically instantaneous contacts. In some cases, edges are active for
non-negligible periods of time: e.g., the proximity patterns of inpatients at
hospitals can be represented by a graph where an edge between two individuals
is on throughout the time they are at the same ward. Like network topology, the
temporal structure of edge activations can affect dynamics of systems
interacting through the network, from disease contagion on the network of
patients to information diffusion over an e-mail network. In this review, we
present the emergent field of temporal networks, and discuss methods for
analyzing topological and temporal structure and models for elucidating their
relation to the behavior of dynamical systems. In the light of traditional
network theory, one can see this framework as moving the information of when
things happen from the dynamical system on the network, to the network itself.
Since fundamental properties, such as the transitivity of edges, do not
necessarily hold in temporal networks, many of these methods need to be quite
different from those for static networks
BClass: A Bayesian Approach Based on Mixture Models for Clustering and Classification of Heterogeneous Biological Data
Based on mixture models, we present a Bayesian method (called BClass) to classify biological entities (e.g. genes) when variables of quite heterogeneous nature are analyzed. Various statistical distributions are used to model the continuous/categorical data commonly produced by genetic experiments and large-scale genomic projects. We calculate the posterior probability of each entry to belong to each element (group) in the mixture. In this way, an original set of heterogeneous variables is transformed into a set of purely homogeneous characteristics represented by the probabilities of each entry to belong to the groups. The number of groups in the analysis is controlled dynamically by rendering the groups as 'alive' and 'dormant' depending upon the number of entities classified within them. Using standard Metropolis-Hastings and Gibbs sampling algorithms, we constructed a sampler to approximate posterior moments and grouping probabilities. Since this method does not require the definition of similarity measures, it is especially suitable for data mining and knowledge discovery in biological databases. We applied BClass to classify genes in RegulonDB, a database specialized in information about the transcriptional regulation of gene expression in the bacterium Escherichia coli. The classification obtained is consistent with current knowledge and allowed prediction of missing values for a number of genes. BClass is object-oriented and fully programmed in Lisp-Stat. The output grouping probabilities are analyzed and interpreted using graphical (dynamically linked plots) and query-based approaches. We discuss the advantages of using Lisp-Stat as a programming language as well as the problems we faced when the data volume increased exponentially due to the ever-growing number of genomic projects.
Tiling solutions for optimal biological sensing
Biological systems, from cells to organisms, must respond to the ever
changing environment in order to survive and function. This is not a simple
task given the often random nature of the signals they receive, as well as the
intrinsically stochastic, many body and often self-organized nature of the
processes that control their sensing and response and limited resources.
Despite a wide range of scales and functions that can be observed in the living
world, some common principles that govern the behavior of biological systems
emerge. Here I review two examples of very different biological problems:
information transmission in gene regulatory networks and diversity of adaptive
immune receptor repertoires that protect us from pathogens. I discuss the
trade-offs that physical laws impose on these systems and show that the optimal
designs of both immune repertoires and gene regulatory networks display similar
discrete tiling structures. These solutions rely on locally non-overlapping
placements of the responding elements (genes and receptors) that, overall,
cover space nearly uniformly.Comment: 11 page
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