Elsevier

Seminars in Nephrology

Volume 30, Issue 5, September 2010, Pages 512-519
Seminars in Nephrology

Understanding Kidney Disease: Toward the Integration of Regulatory Networks Across Species

https://doi.org/10.1016/j.semnephrol.2010.07.008Get rights and content

Summary

Animal models have long been useful in investigating both normal and abnormal human physiology. Systems biology provides a relatively new set of approaches to identify similarities and differences between animal models and human beings that may lead to a more comprehensive understanding of human kidney pathophysiology. In this review, we briefly describe how genome-wide analyses of mouse models have helped elucidate features of human kidney diseases, discuss strategies to achieve effective network integration, and summarize currently available web-based tools that may facilitate integration of data across species. The rapid progress in systems biology and orthology, as well as the advent of web-based tools to facilitate these processes, now make it possible to take advantage of knowledge from distant animal species in targeted identification of regulatory networks that may have clinical relevance for human kidney diseases.

Section snippets

Systems Approaches to Rodent Models of Kidney Pathophysiology

Because of its size, ease of handling, and relative susceptibility to genetic manipulation, the laboratory mouse has become perhaps the major mammalian model of kidney disease over the past few years. The mouse is also genetically and physiologically similar to human beings, and the mouse genome has been sequenced and annotated to a high standard, second only to that of human beings.1, 2 Systems approaches have been applied to the study of kidney diseases in the mouse in several disease models.

Comprehensive Strategy of Network Integration: Tool for Approximate Subgraph Matching of Large Queries Efficiently for Effective Integration of Knowledge from Cross-Species Studies

In addition to the strategies described previously, a more sophisticated use of cross-species gene expression studies compares complex regulatory networks across species for conserved network structures. To best define the shared transcriptional networks between human beings and a mouse model of human nephropathies, an index-based method, a Tool for Approximate Subgraph Matching of Large Queries Efficiently (TALE),23 can be applied. Species-specific transcriptional networks are built using

Web-Based Tools for Effective Integration of Knowledge From Cross-Species Studies

Large sets of genomic and EST-based expression data in various species are more and more accessible to the public, although often these data are stored in heterogeneous formats and scattered over a multitude of species-specific databases (Zebrafish Information Network [ZFIN] for zebrafish,24, 25 Berkeley Drosophila Genome Project [BDGP]26 and Flybase27, 28, 29, 30 for Drosophila, the Gene Expression Database [GXD],31, 32, 33 EMAGE,34, 35, 36 and the GenitoUrinary Development Molecular Anatomy

Outlook

Although we have concentrated our review on mouse models of kidney disease, nonrodent models such as the zebrafish, Danio rerio, the fruitfly, Drosophila melanogaster, and the toad, Xenopus laevis also should be considered for systems biology approaches because they have some advantages over rodent models, including smaller size, shorter generation time, high repopulation rate, and greater ease of genetic manipulation. Kidney systems biology researchers have not yet taken full advantage of

Acknowledgements

The authors thank Viji Nair, Celine Berthier, Markus Bitzer, Felix Eichinger, Sebastian Martini, and Subramaniam Pennathur for insightful discussion and critical reading of the manuscript.

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