Transcriptome signature of the lactation process in a fat-tailed sheep identifies with integrative approach of RNA-Seq and Supervised Machine Learning models

Background: The mammary gland is a vital organ in mammalian that undergoes a substantial physiological transformation during the lactation process. Understanding the underlying molecular mechanism of the lactation process in the mammary gland is essential to unravel of the complexity of milk production process. This study was investigated the transcriptome profiles of milk between two time point of lactation (day 20 as before peak time point (BF) and day 70 as after peak(AF)) in Iranian fat-tailed Ghezel sheep breed. Functional impacts of differentially expressed genes (DEGs) between two time points of the lactation were surveyed with Gene Ontology (GO) and Protein-Protein Interaction (PPI) network analysis. Moreover, to identify the transcriptome signature of the lactation process, supervised machine learning algorithms were integrated. Results Totally, 75 genes were defined as DEGs between BF and AF of lactation. Gene ontology of DEGs mainly enriched in metabolic process and oxidative phosphorylation. Moreover, PPI networks analysis highlighted the contribution of peroxisome proliferator-activated receptors (PPAR) signaling in the lactation process, oxidative phosphorylation and metabolic pathways. These pathways mainly involved in the quality of dairy products and energy generation for milk production. Dissection of DEGs also indicated that the genes encoding for caseins, whey proteins, and enzymes lactose synthesis are dominantly up-regulated after the lactation peak. More interestingly, the genes involved in fat metabolism dominantly down-regulated after the lactation peak. Contribution of nineteen DEGs such as HNRNPA2, CHCHD2, COX1, COX2, GTF3C3, and MRPL11 has verified with more than seven attribute ranking algorithms, which are being proposed as a signature of the lactation process in Ghezel sheep. Conclusions The results of this study highlighted the energy generation, development of immunity, and activation of the immune system in lactation process. To best of our knowledge, this is the first study comparing the underlying mechanism of Ghezel sheep before and after the lactation peak and provides new insight regarding the transcriptional responses for the lactation process.