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Bioinformatics Advance Access published online on February 18, 2007
Bioinformatics, doi:10.1093/bioinformatics/btm042
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© The Author (2007). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Simulating psoriasis by altering transit amplifying cells

Niels Grabe 1,* and Karsten Neuber 2

1Department of Medical Informatics, Institute of Medical Biometry and Informatics, University Hospital Heidelberg, 69120 Heidelberg, Germany and
2Department of Dermatology, University Hospital Hamburg-Eppendorf Martinistrasse 52, 20246 Hamburg, Germany

*To whom correspondence should be addressed. Dr. Niels Grabe, E-mail: niels.grabe{at}med.uni-heidelberg.de, niels.grabe{at}gmail.com


  Abstract

Computational models of tissue homeostasis will facilitate a deeper understanding of many diseases. They link molecular networks, cellular differentiation and the spatial and temporal organization of tissues. Here we show an approach which is able to computationally turn a healthy in-silico epidermis into one with four central properties of psoriatic epidermis. We achieve this by altering a single simulation parameter in the cellular differentiation program of the simulated epidermal keratinocytes: the fractional time period during which transit amplifying cells proliferate ({tau}). Prolonging {tau} results in the four main pathological characteristics of psoriatic skin: (1) an absolute increase of the germinative compartment, (2) an absolute increase of the differentiated compartment, (3) a higher proportion of germinative cells, and (4) a marked reduction in turnover time. The prolongation of {tau} is able to increase the proliferation capacity of the epidermal tissue without altering the cell cycle frequency.

Associate Editor: Satoru Miyano

Received on September 26, 2006; revised on January 11, 2007; accepted on February 4, 2007

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