Abstract
Differential expression analyses provide powerful tools for the identification of genes playing a role in disease pathogenesis. Yet, such approaches are usually restricted by the high variation in expression profiles when primary specimens are analyzed. It is conceivable that with the assessment of the degree of coordination in gene expression as opposed to the magnitude of differential expression, we may obtain hints underscoring different biological and pathological states. Here we have analyzed a publicly available dataset related to frailty, a syndrome characterized by reduced responsiveness to stressors and exhibiting increased prevalence in the elderly. We evaluated the transcriptome that loses its coordination between the frailty and control groups and assessed the biological functions that are acquired in the former group. Among the top genes exhibiting the lowest correlation, at the whole transcriptome level, between the control and frailty groups were TSIX, BEST1 and ADAMTSL4. Processes related to immune response and regulation of cellular metabolism and the metabolism of macromolecules emerged in the frailty group. The proposed strategy confirms and extends earlier findings regarding the pathogenesis of frailty and provides a paradigm on how the diversity in expression profiles of primary specimens could be leveraged for target discovery.
Highlights
Frailty is a clinical syndrome that is characterized by reduced responsiveness to stressors due to physiological decline in multiple organs and is associated with poor health outcomes including falls, incident disability, hospitalization, and mortality [1,2,3,4]
With the number of Americans aged 65 and older projected to double by 2060 [7] frailty consists of a condition with important implications in the quality of life of older individuals and overall healthcare management
It is plausible that the lower degree of correlation in the control group (NOR) is indicative of the margins of expression at which physiological function for these genes can be attained. This flexibility is abolished in frailty because activation of signaling pathways under these conditions dictates more robust expression profiles
Summary
Frailty is a clinical syndrome that is characterized by reduced responsiveness to stressors due to physiological decline in multiple organs and is associated with poor health outcomes including falls, incident disability, hospitalization, and mortality [1,2,3,4]. We have applied an alternative strategy in which samples were evaluated by comparing the correlation of expression of specific genes with the whole transcriptome, in different experimental groups [12, 13].
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