Ritmicidade circadiana e genes correlacionados a genes relógio (CCorGS) identificados em redes de co-expressão no sistema nervoso central de camundongos e humanos

Abstract

Clock-controlled genes (CCG) are crucial components of the molecular network sustaining the circadian rhythm. With transcription regulated by clock genes and high tissue specificity, they play a fundamental role in the circadian regulation of a wide orange of physiological, behavioral, and immunological processes. The CCorGsDB database identified genes correlated with clock genes (CCorGs), potential CCG, through gene co-expression networks in mouse and human brain regions. Since many CCorGs and CCG are drug targets, understanding their circadian expression may offer therapeutic advantages. The application of temporal transcriptomes in conjunction with CCorGsDB can help elucidate the influence of clock genes on the gene expression of CCorGs in different tissues. Thus, the objective of this study was to evaluate the association between the degree of correlation and circadian rhythmicity of CCorGs identified in gene co-expression networks in mouse and human brains from the CCorGsDB database. To achieve this, temporal data from public datasets were subjected to rhythmicity analysis to obtain relative amplitude (rAMP). Differences in correlation within the distribution of rAMPs were assessed using the Mann-Whitney test. Fisher's test was applied to evaluate the enrichment of clock genes among CCorGs in all murine and human regions included in the CCorGsDB. The 95th percentile of rAMP showed higher correlation values compared to the 5th percentile across all analyzed tissues, except for the rostral lateral hypothalamus. Six mouse regions and seven human regions exhibited statistical significance (Fisher p<0.05). These results suggest that regions significant in Fisher's exact test are enriched for clock genes and indicate greater robustness in the expression of genes with higher correlation values in the analyzed areas.