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Open Access Highly Accessed Research article

Archetypal analysis of diverse Pseudomonas aeruginosa transcriptomes reveals adaptation in cystic fibrosis airways

Juliane Charlotte Thøgersen1, Morten Mørup2, Søren Damkiær1, Søren Molin1 and Lars Jelsbak1*

Author Affiliations

1 Department of Systems Biology, Technical University of Denmark, DK-2800 Lyngby, Denmark

2 Department of Applied Mathematics and Computer Science, Technical University of Denmark, DK-2800 Lyngby, Denmark

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BMC Bioinformatics 2013, 14:279  doi:10.1186/1471-2105-14-279

Published: 23 September 2013

Abstract

Background

Analysis of global gene expression by DNA microarrays is widely used in experimental molecular biology. However, the complexity of such high-dimensional data sets makes it difficult to fully understand the underlying biological features present in the data.

The aim of this study is to introduce a method for DNA microarray analysis that provides an intuitive interpretation of data through dimension reduction and pattern recognition. We present the first “Archetypal Analysis” of global gene expression. The analysis is based on microarray data from five integrated studies of Pseudomonas aeruginosa isolated from the airways of cystic fibrosis patients.

Results

Our analysis clustered samples into distinct groups with comprehensible characteristics since the archetypes representing the individual groups are closely related to samples present in the data set. Significant changes in gene expression between different groups identified adaptive changes of the bacteria residing in the cystic fibrosis lung. The analysis suggests a similar gene expression pattern between isolates with a high mutation rate (hypermutators) despite accumulation of different mutations for these isolates. This suggests positive selection in the cystic fibrosis lung environment, and changes in gene expression for these isolates are therefore most likely related to adaptation of the bacteria.

Conclusions

Archetypal analysis succeeded in identifying adaptive changes of P. aeruginosa. The combination of clustering and matrix factorization made it possible to reveal minor similarities among different groups of data, which other analytical methods failed to identify. We suggest that this analysis could be used to supplement current methods used to analyze DNA microarray data.

Keywords:
Archetypal analysis; Gene expression; Pseudomonas aeruginosa; Cystic fibrosis; Hypermutators