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Statistical Assessment of Crosstalk Enrichment between Gene Groups in Biological Networks
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
2013 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 1, e54945- p.Article in journal (Refereed) Published
Abstract [en]

Motivation: Analyzing groups of functionally coupled genes or proteins in the context of global interaction networks has become an important aspect of bioinformatic investigations. Assessing the statistical significance of crosstalk enrichment between or within groups of genes can be a valuable tool for functional annotation of experimental gene sets. Results: Here we present CrossTalkZ, a statistical method and software to assess the significance of crosstalk enrichment between pairs of gene or protein groups in large biological networks. We demonstrate that the standard z-score is generally an appropriate and unbiased statistic. We further evaluate the ability of four different methods to reliably recover crosstalk within known biological pathways. We conclude that the methods preserving the second-order topological network properties perform best. Finally, we show how CrossTalkZ can be used to annotate experimental gene sets using known pathway annotations and that its performance at this task is superior to gene enrichment analysis (GEA). Availability and Implementation: CrossTalkZ (available at http://sonnhammer.sbc.su.se/download/software/CrossTalkZ/) is implemented in C++, easy to use, fast, accepts various input file formats, and produces a number of statistics. These include z-score, p-value, false discovery rate, and a test of normality for the null distributions.

Place, publisher, year, edition, pages
2013. Vol. 8, no 1, e54945- p.
National Category
Bioinformatics and Systems Biology
Research subject
Biochemistry with Emphasis on Theoretical Chemistry
Identifiers
URN: urn:nbn:se:su:diva-88245DOI: 10.1371/journal.pone.0054945ISI: 000314021500148OAI: oai:DiVA.org:su-88245DiVA: diva2:611325
Funder
Swedish Research Council
Note

AuthorCount:4;

Available from: 2013-03-15 Created: 2013-03-12 Last updated: 2017-12-06Bibliographically approved
In thesis
1. Network and gene expression analyses for understanding protein function
Open this publication in new window or tab >>Network and gene expression analyses for understanding protein function
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Biological function is the result of a complex network of functional associations between genes or their products. Modeling the dynamics underlying biological networks is one of the big challenges in bioinformatics. A first step towards solving this problem is to predict and study the networks of functional associations underlying various conditions.

An improved version of the FunCoup network inference method that features networks for three new species and updated versions of the existing networks is presented. Network clustering, i.e. partitioning networks into highly connected components is an important tool for network analysis. We developed MGclus, a clustering method for biological networks that scores shared network neighbors. We found MGclus to perform favorably compared to other methods popular in the field. Studying sets of experimentally derived genes in the context of biological networks is a common strategy to shed light on their underlying biology. The CrossTalkZ method presented in this work assesses the statistical significance of crosstalk enrichment, i.e. the extent of connectivity between or within groups of functionally coupled genes or proteins in biological networks. We further demonstrate that CrossTalkZ is a valuable method to functionally annotate experimentally derived gene sets.

Males and females differ in the expression of an extensive number of genes. The methods developed in the first part of this work were applied to study sex-biased genes in chicken and several network properties related to the molecular mechanisms of sex-biased gene regulation in chicken were deduced. Cancer studies have shown that tumor progression is strongly determined by the tumor microenvironment. We derived a gene expression signature of PDGF-activated fibroblasts that shows a strong prognostic significance in breast cancer in univariate and multivariate survival analyses when compared to established markers for prognosis.

Place, publisher, year, edition, pages
Stockholm: Department of Biochemistry and Biophysics, Stockholm University, 2013. 86 p.
Keyword
biological networks, network inference, network analysis, clustering, network module, network crosstalk, expression analysis, gene signature, biomarker
National Category
Bioinformatics (Computational Biology)
Research subject
Biochemistry with Emphasis on Theoretical Chemistry
Identifiers
urn:nbn:se:su:diva-89055 (URN)978-91-7447-674-3 (ISBN)
Public defence
2013-05-23, Nordenskiöldsalen, Geovetenskapens hus, Svante Arrhenius väg 12, Stockholm, 09:00 (English)
Opponent
Supervisors
Note

At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 5: Accepted.

 

Available from: 2013-05-01 Created: 2013-04-10 Last updated: 2013-04-22Bibliographically approved

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