MOTIVATION: Enhancing the utilization of human-inedible crop by-products by ruminants to produce high-quality milk for human consumption is an emerging global task. We performed a multi-omics-based study to decipher the regulatory biological processes of milk production when cows fed low-quality crop by-products with the aim to improve their utilization. RESULTS: Seven types of different high-throughput omics data were generated across three central organs [rumen, liver and mammary gland (MG)] and biofluids (rumen fluid and blood) that involved in milk production. The integrated multi-omics analysis including metabolomics, metagenomics and transcriptomics showed altered microbiome at compositional and functional levels, microbial metabolites in the rumen, down-regulated genes and associated functions in liver and MG. These changes simultaneously contributed to down-regulated three key metabolic nodes (propionate, glucose and amino acid) across these organs and biofluids that led to lowered milk yield and quality when cows consumed corn stover (CS). Hippuric acid was identified as a biomarker that led to low milk production in CS-fed cows, suggesting a future evaluation parameter related to the metabolic mechanism of low-quality forage utilization. This study unveils the milk production-related biological mechanism across different biofluids and tissues under a low-quality forage diet, which provides a novel understanding and potential improvement strategies for future crop by-products utilization and sustainable ruminant production. AVAILABILITY AND IMPLEMENTATION: The raw files of metagenomics, metabolomics, and transcriptomics data can be accessed at NCBI SRA (No. SRR5028206), EMBI-EBI (No. MTBLS411), and GEO (NO. GSE78524) databases respectively. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

MOTIVATION: Feed efficiency is an important trait for sustainable beef production that is regulated by the complex biological process, but the mode of action behinds it has not been clearly defined. Here, we aimed to elucidate the regulatory mechanisms of this trait through studying the landscape of the genome-wide gene expression of rumen, liver, muscle and backfat tissues, the key ones involved in the energy metabolism. RESULTS: The transcriptome of 189 samples across four tissues from 48 beef steers with varied feed efficiency were generated using Illumina HiSeq4000. The analysis of global gene expression profiles of four tissues, functional analysis of tissue-shared and -unique genes, co-expressed network construction of tissue-shared genes, weighted correlations analysis between gene modules and feed efficiency-related traits in each tissue were performed. Among four tissues, the transcriptome of muscle tissue was distinctive from others, while those of rumen and backfat tissues were similar. The associations between co-expressed genes and feed efficiency related traits at single or all tissues level exhibited that the gene expression in the rumen, liver, muscle and backfat were the most correlated with feed conversion ratio, dry matter intake, average daily gain and residual feed intake, respectively. The 19 overlapped genes identified from the strongest module-trait relationships in four tissues are potential generic gene markers for feed efficiency. AVAILABILITY AND IMPLEMENTATION: The distribution of gene expression data can be accessed at https://www.cattleomics.com/transcriptome. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.