Fonseca Pablo Augusto de Souza, Suarez-Vega Aroa, Esteban-Blanco Cristina, Marina Héctor, Pelayo Rocío, Gutiérrez-Gil Beatriz, Arranz Juan-José
Departamento de Producción Animal, Facultad de Veterinaria, Universidad de León, Campus de Vegazana, Leon, 24007, Spain.
BMC Genomics. 2025 Mar 31;26(1):313. doi: 10.1186/s12864-025-11520-1.
Feed efficiency (FE) is an essential trait in livestock species because of the constant demand to increase the productivity and sustainability of livestock production systems. A better understanding of the biological mechanisms associated with FEs might help improve the estimation and selection of superior animals. In this work, differentially methylated regions (DMRs) were identified via genome-wide bisulfite sequencing (GWBS) by comparing the DNA methylation profiles of milk somatic cells from dairy ewes that were divergent in terms of residual feed intake. The DMRs were identified by comparing divergent groups for residual feed intake (RFI), the feed conversion ratio (FCR), and the consensus between both metrics (Cons). Additionally, the predictive performance of these DMRs and genetic variants mapped within these regions was evaluated via three machine learning (ML) models (xgboost, random forest (RF), and multilayer feedforward artificial neural network (deeplearning)). The average performance of each model was based on the root mean squared error (RMSE) and squared Spearman correlation (rho2). Finally, the best model for each scenario was selected on the basis of the highest ratio between rho2 and RMSE.
In total, 12,257, 9,328, and 6,723 genes were annotated for DMRs detected in the RFI, FCR, and Cons groups, respectively. These genes are associated with important pathways for regulating FE in dairy sheep, such as protein digestion and absorption, hormone synthesis and secretion, control of energy availability, cellular signaling, and feed behavior pathways. With respect to the ML predictions, the smallest mean RMSE (0.17) was obtained using RF, which was used to predict RFI. The highest mean rho (0.20) was obtained when the RFI was predicted via the mean methylation within the DMRs identified, the consensus groups were compared, and the genetic variants mapped within these DMRs were included. The best overall models were obtained for the prediction of RFI using the DMRs obtained in the comparison of RFI groups (RMSE = 0.10, rho = 0.86) using xgboost and the DMRs plus the genetic variants identified via the Cons groups (RMSE = 0.07, rho = 0.62) using RF.
The results provide new insights into the biological mechanisms associated with FE and the control of these processes through epigenetic mechanisms. Additionally, the potential use of epigenetic information as a biomarker for the prediction of FE can be suggested based on the obtained results.
由于不断需要提高畜牧生产系统的生产力和可持续性,饲料效率(FE)是家畜物种的一个重要性状。更好地了解与饲料效率相关的生物学机制可能有助于改进对优良动物的评估和选择。在这项工作中,通过全基因组亚硫酸氢盐测序(GWBS),比较了剩余采食量不同的奶山羊乳腺体细胞的DNA甲基化图谱,从而鉴定出差异甲基化区域(DMR)。通过比较剩余采食量(RFI)、饲料转化率(FCR)的不同组以及这两个指标之间的共识(Cons)来鉴定DMR。此外,通过三种机器学习(ML)模型(XGBoost、随机森林(RF)和多层前馈人工神经网络(深度学习))评估了这些DMR以及这些区域内定位的遗传变异的预测性能。每个模型的平均性能基于均方根误差(RMSE)和平方斯皮尔曼相关性(rho2)。最后,根据rho2与RMSE之间的最高比率为每种情况选择最佳模型。
在RFI、FCR和Cons组中检测到的DMR分别注释了总共12257、9328和6723个基因。这些基因与奶山羊中调节饲料效率的重要途径相关,如蛋白质消化和吸收、激素合成和分泌、能量供应控制、细胞信号传导以及采食行为途径。关于ML预测,使用RF预测RFI时获得了最小的平均RMSE(0.17)。当通过鉴定出的DMR内的平均甲基化预测RFI、比较共识组并纳入这些DMR内定位的遗传变异时,获得了最高的平均rho(0.20)。使用XGBoost通过比较RFI组获得的DMR预测RFI(RMSE = 0.10,rho = 0.86)以及使用RF通过Cons组鉴定的DMR加上遗传变异预测RFI(RMSE = 0.07,rho = 0.62)时,获得了总体最佳模型。
这些结果为与饲料效率相关的生物学机制以及通过表观遗传机制对这些过程的控制提供了新的见解。此外,根据所得结果可以提出将表观遗传信息用作预测饲料效率生物标志物的潜在用途。