Identification of helper T cell master regulator candidates using the polar score method.
The T helper paradigm is currently being revised from the Th1-Th2 dichotomy to a multi-state paradigm involving a number of different cell phenotypes. Transcriptional profiling using microarrays has been used to study the development of these phenotypes. There is however no clear consensus on how to approach the analysis of this data, especially in the context of cells that are triggered to expand rapidly, and massively change their gene expression pattern. We develop a method we call 'polar score' to identify genes that are related to T helper cell polarization. This method is designed to identify polarizing genes in a set where many genes change expression. To illustrate the use of this technique, we apply it to published T cell microarray data and compare it to conventional analysis methods. With the new method, we find evidence for the existence of IL9 producing T cells ('Th9 cells') that are induced by a combination of TGFβ and IL4. We identify several candidate master regulator genes for this phenotype. Furthermore, treatment with TGFβ and IL12 results in a Treg and Th17 hybrid cell phenotype.
van den Ham
H J
HJ
Theoretical Biology and Bioinformatics, Utrecht University, The Netherlands; Department of Virology, Erasmus Medical Center, Rotterdam, The Netherlands. h.j.vandenham@uu.nl
de Waal
L
L
Andeweg
A C
AC
de Boer
R J
RJ
D016764:Cell Polarity / Q000235:genetics / Q000276:immunology*; D019295:Computational Biology / Q000379:methods*; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology; D016906:Interleukin-9 / Q000235:genetics / Q000276:immunology; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000276:immunology
D016906:Interleukin-9; D016212:Transforming Growth Factor beta; D018664:Interleukin-12; D015847:Interleukin-4