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Disease pathways at the Rat Genome Database Pathway Portal: genes in context-a network approach to understanding the molecular mechanisms of disease. Hum Genomics 2014 Sep 30;8:17 PMID: 25265995 PMCID: PMC4191248

Pubmed ID

25265995

Abstract

BACKGROUND: Biological systems are exquisitely poised to respond and adjust to challenges, including damage. However, sustained damage can overcome the ability of the system to adjust and result in a disease phenotype, its underpinnings many times elusive. Unraveling the molecular mechanisms of systems biology, of how and why it falters, is essential for delineating the details of the path(s) leading to the diseased state and for designing strategies to revert its progression. An important aspect of this process is not only to define the function of a gene but to identify the context within which gene functions act. It is within the network, or pathway context, that the function of a gene fulfills its ultimate biological role. Resolving the extent to which defective function(s) affect the proceedings of pathway(s) and how altered pathways merge into overpowering the system's defense machinery are key to understanding the molecular aspects of disease and envisioning ways to counteract it. A network-centric approach to diseases is increasingly being considered in current research. It also underlies the deployment of disease pathways at the Rat Genome Database Pathway Portal. The portal is presented with an emphasis on disease and altered pathways, associated drug pathways, pathway suites, and suite networks.

RESULTS: The Pathway Portal at the Rat Genome Database (RGD) provides an ever-increasing collection of interactive pathway diagrams and associated annotations for metabolic, signaling, regulatory, and drug pathways, including disease and altered pathways. A disease pathway is viewed from the perspective of networks whose alterations are manifested in the affected phenotype. The Pathway Ontology (PW), built and maintained at RGD, facilitates the annotations of genes, the deployment of pathway diagrams, and provides an overall navigational tool. Pathways that revolve around a common concept and are globally connected are presented within pathway suites; a suite network combines two or more pathway suites.

CONCLUSIONS: The Pathway Portal is a rich resource that offers a range of pathway data and visualization, including disease pathways and related pathway suites. Viewing a disease pathway from the perspective of underlying altered pathways is an aid for dissecting the molecular mechanisms of disease.

Author List

Petri V, Hayman GT, Tutaj M, Smith JR, Laulederkind SJ, Wang SJ, Nigam R, De Pons J, Shimoyama M, Dwinell MR, Worthey EA, Jacob HJ

Authors

Melinda R. Dwinell PhD Center Associate Director, Associate Professor in the Physiology department at Medical College of Wisconsin
Mary E. Shimoyama PhD Associate Professor in the Biomedical Engineering department at Medical College of Wisconsin




Scopus

2-s2.0-84964312855   5 Citations

MESH terms used to index this publication - Major topics in bold

Animals
Databases, Genetic
Disease Models, Animal
Female
Gene Regulatory Networks
Genome
Male
Metabolic Networks and Pathways
Molecular Sequence Annotation
Phenotype
Rats
Signal Transduction
Systems Biology
User-Computer Interface
jenkins-FCD Prod-296 4db9d02597e0a2e889e230f853b641c12f1c3ee3