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Bioinformatics 2007 23(23):3200-3208; doi:10.1093/bioinformatics/btm504
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© The Author 2007. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Reconstructing protein networks of epithelial differentiation from histological sections

Niels Grabe 1,2,*, Thora Pommerencke 1,2, Thorsten Steinberg 1,3, Hartmut Dickhaus 1,2 and Pascal Tomakidi 1,3

1Hamamatsu Tissue Imaging and Analysis (TIGA) Center, BIOQUANT, University Heidelberg, BQ0010, Im Neuenheimer Feld 267, 2Institute for Medical Biometry and Informatics, University Hospital Heidelberg, Im Neuenheimer Feld 305 and 3Department of Orthodontics and Dentofacial Orthopedics, Dental School University of Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany

*To whom correspondence should be addressed.


  Abstract

Motivation: For systems biology of complex stratified epithelia like human epidermis, it will be of particular importance to reconstruct the spatiotemporal gene and protein networks regulating keratinocyte differentiation and homeostasis.

Results: Inside the epidermis, the differentiation state of individual keratinocytes is correlated with their respective distance from the connective tissue. We here present a novel method to profile this correlation for multiple epithelial protein biomarkers in the form of quantitative spatial profiles. Profiles were computed by applying image processing algorithms to histological sections stained with tri-color indirect immunofluorescence. From the quantitative spatial profiles, reflecting the spatiotemporal changes of protein expression during cellular differentiation, graphs of protein networks were reconstructed.

Conclusion: Spatiotemporal networks can be used as a means for comparing and interpreting quantitative spatial protein expression profiles obtained from different tissue samples. In combination with automated microscopes, our new method supports the large-scale systems biological analysis of stratified epithelial tissues.

Contact: niels.grabe{at}med.uni-heidelberg.de

Associate Editor: Limsoon Wong

Received on July 9, 2007; revised on September 14, 2007; accepted on October 3, 2007

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