Multiplexed Visualization Method to Explore Complete Targeting Regulatory Relationships Among Circadian Genes for Insomnia Treatment

Abstract

Understanding the complete map of melatonin synthesis, the information transfer network among circadian genes in pineal gland, promises to resolve outstanding issues in endocrine systems and improve the clinical diagnosis and treatment level of insomnia, immune disease and hysterical depression. Currently, some landmark studies have revealed some genes that regulate circadian rhythm associated with melatonin synthesis. However, these studies don't give a complete map of melatonin synthesis, as transfer information among circadian genes in pineal gland is lost. New biotechnology, integrates dynamic sequential omics and multiplexed imaging method, has been used to visualize the complete process of melatonin synthesis. It is found that there are two extremely significant information transfer processes involved in melatonin synthesis. In the first stage, as the light intensity decreased, melatonin synthesis mechanism has started, which is embodied in circadian genes, Rel, Polr2A, Mafk, and Srbf1 become active. In the second stage, circadian genes Hif1a, Bach1, Clock, E2f6, and Per2 are regulated simultaneously by four genes, Rel, Polr2A, Mafk, and Srbf1 and contribute genetic information to Aanat. The expeditious growth in this technique offer reference for an overall understanding of gene-to-gene regulatory relationship among circadian genes in pineal gland. In the study, dynamic sequential omics and the analysis process well provide the current state and future perspectives to better diagnose and cure diseases associated with melatonin synthesis disorder.

Inferring circadian gene regulatory relationships from gene expression data with a hybrid framework

“…The data of time-series expression profiles of rats were obtained from the laboratory of Inner Mongolia Agricultural University (Inner Mongolia Autonomous Region Key Laboratory of Big Data Research and Application for Agricultural and Animal Husbandry) and uploaded to the NCBI SRA database [ 23 ]. The purpose of acquiring the data was to obtain the circadian genes that regulate the sleep of rats through the analysis of time-series gene expression data.…”

Inferring Circadian Gene Regulatory Relationships from Gene Expression Data with a Hybrid Framework

“…The data of time-series expression profiles of rats in this paper were obtained from the laboratory of Inner Mongolia Agricultural University (Inner Mongolia Autonomous Region Key Laboratory of Big Data Research and Application for Agricultural and Animal Husbandry) and has been uploaded to the NCBI SRA database [19]. The purpose of acquiring the data was to obtain the circadian genes that regulate the sleep of rats through the analysis of time-series gene expression data.…”

“…There are seven main steps for the experiment: (1) Take the rat to the test bench; (2) Euthanize the rat by decapitation; (3) Open the skull and take out the brain tissues; (4) Isolate the rhythm centre-pineal gland; (5) Identify second microstructure; (6) Remove rat pineal gland and put it in a 2 ml Corning Freezer Tube; (7) Label the sample and cryopreserved in liquid nitrogen immediately. More experimental details can be found in [19,20].…”

“…More specifically, we will focus on inferring gene regulatory relationships that contribute genetic information to Aanat. Li et al [19] validated that "N-acetyltransferase gene (Aanat) is a potential target gene for melatonin rhythm regulation in rat pineal gland". Therefore, the Aanat gene is chosen as our target gene in this study.…”

“…The raw gene expression data are available for download at Sequence Read Archive (SRA) (SRR18934928 -SRR18935407) on the National Library of Medicine website. More details about this dataset can be found in [19].…”