Skip Navigation


Bioinformatics Advance Access originally published online on September 10, 2009
Bioinformatics 2009 25(22):2891-2896; doi:10.1093/bioinformatics/btp538
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (Print PDF) Freely available
Right arrow Supplementary Data
Right arrowOA All Versions of this Article:
25/22/2891    most recent
btp538v1
Right arrow Comments: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when Comments are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Google Scholar
Right arrow Articles by Sadreyev, R. I.
Right arrow Articles by Grishin, N. V.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sadreyev, R. I.
Right arrow Articles by Grishin, N. V.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author(s) 2009. Published by Oxford University Press.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Phenotypic categorization of genetic skin diseases reveals new relations between phenotypes, genes and pathways

Ruslan I. Sadreyev 1, Jamison D. Feramisco 2, Hensin Tsao 3,* and Nick V. Grishin 1,4,*

1Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-9050, 2Department of Dermatology, University of California at San Francisco, San Francisco, CA 94115, 3Wellman Center for Photomedicine, Department of Dermatology, Massachusetts General Hospital, 55 Fruit St, Boston, MA 02114, and 4Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-9050, USA

*To whom correspondence should be addressed.


  Abstract

Motivation: Systematic analysis of connection between proteins, their cellular function and phenotypic manifestations in disease is a central problem of biological and clinical research. The solution to this problem requires the development of new approaches to link the rapidly growing dataset of gene–disease associations with the many complex and overlapping phenotypes of human disease.

Results: We analyze genetic skin disorders and suggest a manually designed set of elementary phenotypes whose combinations define diseases as points in a multidimensional space, providing a basis for phenotypic disease clustering. Placing the known gene–disease associations in the context of this space reveals new patterns that suggest previously unknown functional links between proteins, signaling pathways and disease phenotypes. For example, analysis of telangiectasias (spider vein diseases) reveals a previously unrecognized interplay between the TGF-β signaling pathway and pentose phosphate pathway. This interaction may mediate glucose-dependent regulation of TGF-β signaling, providing a clue to the known association between angiopathies and diabetes and implying new gene candidates for mutational analysis and drug targeting.

Contact: grishin{at}chop.swmed.edu

Supplementary information: Supplementary data are available at Bioinformatics online.

Associate Editor: Jonathan Wren

Received on May 11, 2009; revised on August 10, 2009; accepted on September 7, 2009

Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.