Machine Learning-Based Co-Expression Network Analysis Unravels Potential Fertility-Related Genes in Beef Cows

SIMPLE SUMMARY: Female reproductive failure is still a challenge for the beef industry. Several biological processes that underlie fertility-related traits, such as the establishment of pregnancy and embryo survival, are still unclear. Increased availability of transcriptomic data has allowed a deep investigation of the potential mechanisms involved in fertility. This study investigated candidate gene biomarkers predictive of pregnancy status and underlying fertility-related networks. To this end, we integrated gene expression profiles through supervised machine learning and gene network modeling. We identified nine biologically relevant endometrial gene biomarkers that could discriminate against pregnancy status in cows. These biomarkers were co-expressed with genes critical for uterine receptivity, including endometrial tissue remodeling, focal adhesion, and embryo development. This study outlined key pathways involved with pregnancy success and provided predictive candidate biomarkers for pregnancy outcome in cows. ABSTRACT: Reproductive failure is still a challenge for beef producers and a significant cause of economic loss. The increased availability of transcriptomic data has shed light on the mechanisms modulating pregnancy success. Furthermore, new analytical tools, such as machine learning (ML), provide opportunities for data mining and uncovering new biological events that explain or predict reproductive outcomes. Herein, we identified potential biomarkers underlying pregnancy status and fertility-related networks by integrating gene expression profiles through ML and gene network modeling. We used public transcriptomic data from uterine luminal epithelial cells of cows retrospectively classified as pregnant (P, n = 25) and non-pregnant (NP, n = 18). First, we used a feature selection function from BioDiscML and identified SERPINE3, PDCD1, FNDC1, MRTFA, ARHGEF7, MEF2B, NAA16, ENSBTAG00000019474, and ENSBTAG00000054585 as candidate biomarker predictors of pregnancy status. Then, based on co-expression networks, we identified seven genes significantly rewired (gaining or losing connections) between the P and NP networks. These biomarkers were co-expressed with genes critical for uterine receptivity, including endometrial tissue remodeling, focal adhesion, and embryo development. We provided insights into the regulatory networks of fertility-related processes and demonstrated the potential of combining different analytical tools to prioritize candidate genes.