Table_6_Systems Biology Reveals NR2F6 and TGFB1 as Key Regulators of Feed Efficiency in Beef Cattle.XLSX

Systems biology approaches are used as strategy to uncover tissue-specific perturbations and regulatory genes related to complex phenotypes. We applied this approach to study feed efficiency (FE) in beef cattle, an important trait both economically and environmentally. Poly-A selected RNA of five tissues (adrenal gland, hypothalamus, liver, skeletal muscle and pituitary) of eighteen young bulls, selected for high and low FE, were sequenced (Illumina HiSeq 2500, 100 bp, pared-end). From the 17,354 expressed genes considering all tissues, 1,335 were prioritized by five selection categories (differentially expressed, harboring SNPs associated with FE, tissue-specific, secreted in plasma and key regulators) and used for network construction. NR2F6 and TGFB1 were identified and validated by motif discovery as key regulators of hepatic inflammatory response and muscle tissue development, respectively, two biological processes demonstrated to be associated with FE. Moreover, we indicated potential biomarkers of FE, which are related to hormonal control of metabolism and sexual maturity. By using robust methodologies and validation strategies, we confirmed the main biological processes related to FE in Bos indicus and indicated candidate genes as regulators or biomarkers of superior animals.

本研究采用系统生物学策略，旨在挖掘与复杂表型相关的组织特异性扰动及调控基因。我们将该策略应用于肉牛饲料转化率（Feed Efficiency, FE）的研究——饲料转化率是兼具经济与环境重要性的性状。本研究对18头按高低饲料转化率分组的青年公牛的5种组织（肾上腺、下丘脑、肝脏、骨骼肌、垂体）进行聚腺苷酸富集RNA（Poly-A selected RNA）测序，测序平台为Illumina HiSeq 2500，读长100 bp，采用双端测序模式。在所有组织共检测到的17354个表达基因中，我们通过5类筛选标准（差异表达基因、携带与饲料转化率相关的单核苷酸多态性（Single Nucleotide Polymorphisms, SNPs）基因、组织特异性基因、血浆分泌蛋白编码基因及关键调控基因）优先筛选出1335个基因，用于构建基因调控网络。通过基序发现分析，本研究鉴定并验证了NR2F6和TGFB1分别作为肝脏炎症反应和肌肉组织发育的关键调控因子，而这两类生物学过程已被证实与饲料转化率相关。此外，本研究还筛选出与代谢激素调控及性成熟相关的饲料转化率潜在生物标志物。本研究通过严谨的实验方法与验证策略，证实了瘤牛（Bos indicus）中与饲料转化率相关的核心生物学过程，并筛选出可作为优良肉牛调控因子或生物标志物的候选基因。