Abstract
The paper presents the results of a study of the tissuespecificity of the circadian phase characteristics of biological processes in the mouse liver and kidneys. We performed a comparative analysis of the translatomes in these two organs based on experimental data on the daily dynamics of the level of translation of mouse genes from the GEO database (GSE67305 and GSE81283) obtained by ribosome profiling. Genes with a pronounced daily dynamics of translation were revealed (3 358 genes in the liver and 2 938 in the kidneys). Further, for each of the 12 time points (ZT0–ZT22), for each tissue (liver, kidneys), groups of genes that were in a phase with an increased level of translation were identified. It was assumed that the gene is in a phase with an increased level of translation if at a given time point its ribosome profiling rate for both replicas exceeded the daily average value for this gene. The greatest number of rhythmic genes in the liver has an increased level of translation at the beginning of the dark phase of the day corresponding to increased animal activity. In the kidneys, the differences in the distribution of the number of genes in the phase of an elevated translation level by the time of day were less pronounced, and the maximum number of such genes was observed from the middle of the light phase of the day to the middle of the dark one. A statistical analysis of enrichment of Gene Ontology terms in these twelve gene groups in the liver and kidneys was perform ed. Analyzing the processes, the rhythmicity of which is typical of both liver and kidneys, we have identified the processes, the circadian phase characteristics of which in these tissues coincide and the processes having essentially different temporal phase patterns for these tissues. Processes with strict tissuespecific rhythmic translation have also been identified. The approach used in our work allows us to analyze the organo/tissuespecificity of the phase characteristics of biological processes, and the results emphasize the need to take into account the phase circadian characteristics when comparing the features of the course of biological processes in various organs.
Highlights
The paper presents the results of a study of the tissue-spe cificity of the circadian phase characteristics of biological processes in the mouse liver and kidneys
We performed a comparative analysis of the translatomes in these two organs based on experimental data on the daily dynamics of the level of translation of mouse genes from the GEO database (GSE67305 and GSE81283) obtained by ribo some profiling
The rhythmicity of which is typical of both liver and kidneys, we have identified the processes, the circadian phase characteristics of which in these tissues coincide and the processes having essentially different temporal phase patterns for these tissues
Summary
В статье представлены результаты исследования тканеспеци фичности циркадных фазовых характеристик биологических процессов в печени и почках мыши. Основываясь на экспери ментальных данных по суточной динамике уровня трансляции генов мыши из базы данных GEO (GSE67305 и GSE81283), полу ченных методом профилирования рибосом в печени и почках, мы провели сравнительный анализ транслятомов в этих двух органах. В настоящей работе мы провели сравнительный анализ транслятомов печени и почек мыши, представленных в исследованиях (Janich et al, 2015; Castelo-Szekely et al, 2017), выявили гены, имеющие выраженную суточную динамику трансляции, определили периоды времени, когда она достигает максимального уровня. Идентификация генов, демонстрирующих циркадную ритмику трансляции, была осуществлена методом, основанным на комбинации критерия, используемого в программе eJTK_CYCLE (empP < 0.05) (Hughes et al, 2010; Hutchison et al, 2015), с последующим анализом разброса измерений в каждой временной точке суточного ритма для выявления устойчивых паттернов экспрессии, воспроизводимых в каждом суточном цикле наблюдения для нескольких реплик (в нашем случае две реплики). Показатель empP в программе eJTK_CYCLE соответствует эмпирической оценке уровня значимости (p-value) с учетом множественности выбора, полученной путем имитационного моделирования (Hutchison et al, 2015)
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