Disease pathways at the Rat Genome Database Pathway Portal: genes in context¿a network approach to understanding the molecular mechanisms of disease

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.

Genetic Dissection of Femoral and Tibial Microarchitecture

“…We compared all 16 bone QTL with hundreds of rodent bone loci listed in the RGD . Of these 16, 3 are completely novel: 1 on Chr 6 ( Tcv2 ) and 2 loci on Chr X ( FcvX and FcvfX ).…”

The Rat Genome Database 2015: genomic, phenotypic and environmental variations and disease

“…The focus on environment and experimental conditions has also extended to the pathway portal at RGD ( 9,10 ) with expansions of regulatory and drug pathway diagram pages. These include those related to hypoxia, stress response, titanium dioxide nanoparticle response and toxic response to drugs such as acetaminophen and cisplatin (Figure 5 ).…”

“…RGD also provides an expanding set of pharmacokinetic and pharmacodynamics pathways for drugs used to control diabetes, cardiovascular diseases and cancer. These and all pathway diagrams are manually built using the research literature for context and the Pathway Studio software from Elsevier for graphics; the diagram pages are created using a web application tool built at RGD ( 9,10 ).…”

“…This resource has increased in value as strain-specific phenotypic and genomic profiles have been generated in the past several years as described below. RGD's multiple innovative software tools and resources, including multiple Genome Browsers ( 3,4 ), Disease Portals ( 4,5 ), Ontology Browser ( 6 ), PhenoMiner ( 7,8 ) and Pathway Portal ( 9,10 ) make it an extensive research platform and provide navigation among multiple data types and opportunities for data analysis.…”

Disease, Models, Variants and Altered Pathways—Journeying RGD Through the Magnifying Glass

“…In addition, there are terms and associated diagrams for the altered version(s) of pathway(s). A disease pathway is viewed as the intersection of altered pathways converging into the disease phenotype [29] , [30] . Many, if not most, of the pathways of glucose metabolism have interactive diagram pages while others are dedicated to insulin secretion, insulin and glucagon signaling and the downstream cascades they activate, glucose uptake, altered pathways relevant to T2D, the T2D disease pathway and the pharmacokinetics and pharmacodynamics pathways of several drugs used in T2D treatment.…”