Genome-Wide Gene-Environment Interaction Analysis Identifies Novel Candidate Variants for Growth Traits in Beef Cattle.

Complex traits are widely considered to be the result of a compound regulation of genes, environmental factors, and genotype-by-environment interaction (G × E). The inclusion of G × E in genome-wide association analyses is essential to understand animal environmental adaptations and improve the efficiency of breeding decisions. Here, we systematically investigated the G × E of growth traits (including weaning weight, yearling weight, 18-month body weight, and 24-month body weight) with environmental factors (farm and temperature) using genome-wide genotype-by-environment interaction association studies (GWEIS) with a dataset of 1350 cattle. We validated the robust estimator's effectiveness in GWEIS and detected 29 independent interacting SNPs with a significance threshold of 1.67 × 10-6, indicating that these SNPs, which do not show main effects in traditional genome-wide association studies (GWAS), may have non-additive effects across genotypes but are obliterated by environmental means. The gene-based analysis using MAGMA identified three genes that overlapped with the GEWIS results exhibiting G × E, namely SMAD2, PALMD, and MECOM. Further, the results of functional exploration in gene-set analysis revealed the bio-mechanisms of how cattle growth responds to environmental changes, such as mitotic or cytokinesis, fatty acid ß-oxidation, neurotransmitter activity, gap junction, and keratan sulfate degradation. This study not only reveals novel genetic loci and underlying mechanisms influencing growth traits but also transforms our understanding of environmental adaptation in beef cattle, thereby paving the way for more targeted and efficient breeding strategies.

Genome-Wide Detection of Copy Number Variations and Their Potential Association with Carcass and Meat Quality Traits in Pingliang Red Cattle.

Copy number variation (CNV) serves as a significant source of genetic diversity in mammals and exerts substantial effects on various complex traits. Pingliang red cattle, an outstanding indigenous resource in China, possess remarkable breeding value attributed to their tender meat and superior marbling quality. However, the genetic mechanisms influencing carcass and meat quality traits in Pingliang red cattle are not well understood. We generated a comprehensive genome-wide CNV map for Pingliang red cattle using the GGP Bovine 100K SNP chip. A total of 755 copy number variable regions (CNVRs) spanning 81.03 Mb were identified, accounting for approximately 3.24% of the bovine autosomal genome. Among these, we discovered 270 potentially breed-specific CNVRs in Pingliang red cattle, including 143 gains, 73 losses, and 54 mixed events. Functional annotation analysis revealed significant associations between these specific CNVRs and important traits such as carcass and meat quality, reproduction, exterior traits, growth traits, and health traits. Additionally, our network and transcriptome analysis highlighted CACNA2D1, CYLD, UBXN2B, TG, NADK, and ITGA9 as promising candidate genes associated with carcass weight and intramuscular fat deposition. The current study presents a genome-wide CNV map in Pingliang red cattle, highlighting breed-specific CNVRs, and transcriptome findings provide valuable insights into the underlying genetic characteristics of Pingliang red cattle. These results offer potential avenues for enhancing meat quality through a targeted breeding program.

Determining toxicity of europium oxide nanoparticles in immune cell components and hematopoiesis in dominant organs in mice: Role of lysosomal fluid interaction.

Extensive application of rare earth element oxide nanoparticles (REE NPs) has raised a concern over the possible toxic health effects after human exposure. Once entering the body, REE NPs are primarily processed by phagocytes in particular macrophages and undergo biotic phosphate complexation in lysosomal compartment. Such biotransformation affects the target organs and in vivo fate of REE NPs after escaping the lysosomes. However, the immunomodulatory effects of intraphagolysosomal dissolved REE NPs remains insufficient. Here, europium oxide (Eu2O3) NPs were pre-incubated with phagolysosomal simulant fluid (PSF) to mimic the biotransformation of europium oxide (p-Eu2O3) NPs under acid phagolysosome conditions. We investigated the alteration in immune cell components and the hematopoiesis disturbance on adult mice after intravenous administration of Eu2O3 NPs and p-Eu2O3 NPs. Our results indicated that the liver and spleen were the main target organs for Eu2O3 NPs and p-Eu2O3 NPs. Eu2O3 NPs had a much higher accumulative potential in organs than p-Eu2O3 NPs. Eu2O3 NPs induced more alterations in immune cells in the spleen, while p-Eu2O3 NPs caused stronger response in the liver. Regarding hematopoietic disruption, Eu2O3 NPs reduced platelets (PLTs) in peripheral blood, which might be related to the inhibited erythrocyte differentiation in the spleen. By contrast, p-Eu2O3 NPs did not cause significant disturbance in peripheral PLTs. Our study demonstrated that the preincubation with PSF led to a distinct response in the immune system compared to the pristine REE NPs, suggesting that the potentially toxic effects induced by the release of NPs after phagocytosis should not be neglected, especially when evaluating the safety of NPs application in vivo.

Transcriptome Analysis of Compensatory Growth and Meat Quality Alteration after Varied Restricted Feeding Conditions in Beef Cattle.

Compensatory growth (CG) is a physiological response that accelerates growth following a period of nutrient limitation, with the potential to improve growth efficiency and meat quality in cattle. However, the underlying molecular mechanisms remain poorly understood. In this study, 60 Huaxi cattle were divided into one ad libitum feeding (ALF) group and two restricted feeding groups (75% restricted, RF75; 50% restricted, RF50) undergoing a short-term restriction period followed by evaluation of CG. Detailed comparisons of growth performance during the experimental period, as well as carcass and meat quality traits, were conducted, complemented by a comprehensive transcriptome analysis of the longissimus dorsi muscle using differential expression analysis, gene set enrichment analysis (GSEA), gene set variation analysis (GSVA), and weighted correlation network analysis (WGCNA). The results showed that irrespective of the restriction degree, the restricted animals exhibited CG, achieving final body weights comparable to the ALF group. Compensating animals showed differences in meat quality traits, such as pH, cooking loss, and fat content, compared to the ALF group. Transcriptomic analysis revealed 57 genes and 31 pathways differentially regulated during CG, covering immune response, acid-lipid metabolism, and protein synthesis. Notably, complement-coagulation-fibrinolytic system synergy was identified as potentially responsible for meat quality optimization in RF75. This study provides novel and valuable genetic insights into the regulatory mechanisms of CG in beef cattle.

Improving Genomic Predictions in Multi-Breed Cattle Populations: A Comparative Analysis of BayesR and GBLUP Models.

Numerous studies have shown that combining populations from similar or closely related genetic breeds improves the accuracy of genomic predictions (GP). Extensive experimentation with diverse Bayesian and genomic best linear unbiased prediction (GBLUP) models have been developed to explore multi-breed genomic selection (GS) in livestock, ultimately establishing them as successful approaches for predicting genomic estimated breeding value (GEBV). This study aimed to assess the effectiveness of using BayesR and GBLUP models with linkage disequilibrium (LD)-weighted genomic relationship matrices (GRMs) for genomic prediction in three different beef cattle breeds to identify the best approach for enhancing the accuracy of multi-breed genomic selection in beef cattle. Additionally, a comparison was conducted to evaluate the predictive precision of different marker densities and genetic correlations among the three breeds of beef cattle. The GRM between Yunling cattle (YL) and other breeds demonstrated modest affinity and highlighted a notable genetic concordance of 0.87 between Chinese Wagyu (WG) and Huaxi (HX) cattle. In the within-breed GS, BayesR demonstrated an advantage over GBLUP. The prediction accuracies for HX cattle using the BayesR model were 0.52 with BovineHD BeadChip data (HD) and 0.46 with whole-genome sequencing data (WGS). In comparison to the GBLUP model, the accuracy increased by 26.8% for HD data and 9.5% for WGS data. For WG and YL, BayesR doubled the within-breed prediction accuracy to 14.3% from 7.1%, outperforming GBLUP across both HD and WGS datasets. Moreover, analyzing multiple breeds using genomic selection showed that BayesR consistently outperformed GBLUP in terms of predictive accuracy, especially when using WGS. For instance, in a mixed reference population of HX and WG, BayesR achieved a significant accuracy of 0.53 using WGS for HX, which was a substantial enhancement over the accuracies obtained with GBLUP models. The research further highlights the benefit of including various breeds in the reference group, leading to enhanced accuracy in predictions and emphasizing the importance of comprehensive genomic selection methods. Our research findings indicate that BayesR exhibits superior performance compared to GBLUP in multi-breed genomic prediction accuracy, achieving a maximum improvement of 33.3%, especially in genetically diverse breeds. The improvement can be attributed to the effective utilization of higher single nucleotide polymorphism (SNP) marker density by BayesR, resulting in enhanced prediction accuracy. This evidence conclusively demonstrates the significant impact of BayesR on enhancing genomic predictions in diverse cattle populations, underscoring the crucial role of genetic relatedness in selection methodologies. In parallel, subsequent studies should focus on refining GRM and exploring alternative models for GP.

Genetic Origin and Introgression Pattern of Pingliang Red Cattle Revealed Using Genome-Wide SNP Analyses.

The Pingliang red cattle, an outstanding indigenous resource in China, possesses an exceptional breeding value attributed to its tender meat and superior marbling quality. Currently, research efforts have predominantly concentrated on exploring its maternal origin and conducting conventional phenotypic studies. However, there remains a lack of comprehensive understanding regarding its genetic basis. To address this gap, we conducted a thorough whole-genome analysis to investigate the population structure, phylogenetic relationships, and gene flows of this breed using genomic SNP chip data from 17 bovine breeds. The results demonstrate that Pingliang red cattle have evolved distinct genetic characteristics unique to this breed, clearly distinguishing it from other breeds. Based on the analysis of the population structure and phylogenetic tree, it can be classified as a hybrid lineage between Bos taurus and Bos indicus. Furthermore, Pingliang red cattle display a more prominent B. taurus pedigree in comparison with Jinnan, Qinchuan, Zaosheng, Nanyang, and Luxi cattle. Moreover, this study also revealed closer genetic proximity within the Chinese indigenous cattle breed, particularly Qinchuan cattle, which shares the longest identical by descent (IBD) fragment with Pingliang red cattle. Gene introgression analysis shows that Pingliang red cattle have undergone gene exchange with South Devon and Red Angus cattle from Europe. Admixture analysis revealed that the proportions of East Asian taurine and Chinese indicine in the ancestry of Pingliang red cattle are approximately 52.44% and 21.00%, respectively, while Eurasian taurine, European taurine, and Indian indicine account for approximately 17.55%, 7.27%, and 1.74%. Our findings unveil distinct genetic characteristics in Pingliang red cattle and attribute their origin to B. taurus and B. indicus ancestry, as well as contributions from Qinchuan cattle, South Devon, and Red Angus.

Genome-Wide Association Analysis Identifies the PMEL Gene Affecting Coat Color and Birth Weight in Simmental × Holstein.

Coat color and birth weight, as easily selected traits in cattle, play important roles in cattle breeding. Therefore, we carried out a genome-wide association study on birth weight and coat color to identify loci or potential linkage regions in 233 Simmental × Holstein crossbred beef cattle. The results revealed that nine SNPs were significantly associated with coat color (rs137169378, rs110022687, rs136002689, Hypotrichosis_PMel17, PMEL_1, rs134930689, rs383170073, rs109924971, and rs109146332), and these were in RNF41, ZC3H10, ERBB3, PMEL, and OR10A7 on BTA5. Interestingly, rs137169378, rs110022687, rs136002689, Hypotrichosis_PMel17, and PMEL_1 showed strong linkage disequilibrium (r2 > 0.8) and were significantly associated with coat color. Notably, Hypotrichosis_PMel17 and PMEL_1 were located in the gene PMEL (p = 2.22 × 10-18). Among the five significant SNPs associated with coat color, the birth weight of heterozygous individuals (AB) was greater than that of homozygous individuals (AA). Notably, the birth weight of heterozygous individuals with Hypotrichosis_PMel17 and PMEL_1 genotypes was significantly greater than that of homozygous individuals (0.01 < p < 0.05). Interestingly, the two loci were homozygous in black/white individuals and heterozygous in gray/white individuals, and the birth weight of heterozygous brown/white individuals (43.82 ± 5.25 kg) was greater than that of homozygous individuals (42.58 ± 3.09 kg). The birth weight of calves with the parental color (41.95 ± 3.53 kg) was significantly lower than that of calves with a non-parental color (43.54 ± 4.78 kg) (p < 0.05), and the birth weight of gray/white individuals (49.40 ± 7.11 kg) was the highest. Overall, PMEL appears to be a candidate gene affecting coat color in cattle, and coat color may have a selective effect on birth weight. This study provides a foundation for the breeding of beef cattle through GWAS for coat color and birth weight.

Genetic Association Analysis of Copy Number Variations for Meat Quality in Beef Cattle.

Meat quality is an economically important trait for global food production. Copy number variations (CNVs) have been previously implicated in elucidating the genetic basis of complex traits. In this article, we detected a total of 112,198 CNVs and 10,102 CNV regions (CNVRs) based on the Bovine HD SNP array. Next, we performed a CNV-based genome-wide association analysis (GWAS) of six meat quality traits and identified 12 significant CNV segments corresponding to eight candidate genes, including PCDH15, CSMD3, etc. Using region-based association analysis, we further identified six CNV segments relevant to meat quality in beef cattle. Among these, TRIM77 and TRIM64 within CNVR4 on BTA29 were detected as candidate genes for backfat thickness (BFT). Notably, we identified a 34 kb duplication for meat color (MC) which was supported by read-depth signals, and this duplication was embedded within the keratin gene family including KRT4, KRT78, and KRT79. Our findings will help to dissect the genetic architecture of meat quality traits from the aspects of CNVs, and subsequently improve the selection process in breeding programs.

Caffeic acid phenethyl ester inhibits MDA-MB-231 cell proliferation in inflammatory microenvironment by suppressing glycolysis and lipid metabolism.

Caffeic acid phenethyl ester (CAPE) is one of the main active ingredients of propolis with good antitumor activities. However, the potential effects of CAPE on the glycolysis and lipid metabolism of tumor cells are unclear. Here, the anti-tumor effects of CAPE on MDA-MB-231 cells in an inflammatory microenvironment stimulated with lipopolysaccharide (LPS) were studied by estimating the inflammatory mediators and the key factors of glycolysis and lipid metabolism. The CAPE treatment obviously inhibited proliferation, migration, invasion, and angiogenesis, and the mitochondrial membrane potential was decreased in the LPS-stimulated MDA-MB-231 cells. Compared with the LPS group, pro-inflammatory mediators, including toll-like receptor 4 (TLR4), tumor necrosis factor alpha (TNF-α), NF-kappa-B inhibitor alpha (IκBα), interleukin (IL)-1ß, and IL-6, as well as interleukin-1 receptor-associated kinase 4 (IRAK4), declined after the CAPE treatment. Additionally, CAPE significantly down-regulated the levels of glucose transporter 1 (GLUT1), glucose transporter 3 (GLUT3), and the key enzymes of glycolysis-hexokinase 2 (HK2), phosphofructokinase (PFK), pyruvate kinase muscle isozyme M2 (PKM2), and lactate dehydrogenase A (LDHA). Moreover, CAPE treatment decreased the levels of key lipid metabolism proteins, including acetyl coenzyme A carboxylase (ACC), fatty acid synthase (FASN), and free fatty acid (FFA)-transported-related protein CD36. After adding the glycolysis inhibitor 2-deoxy-D-glucose (2-DG), the inhibitory effects of CAPE on cell viability and migration were not significant when compared with the LPS group. In summary, the antitumor activity of CAPE in vitro was mainly via the modulation of the inflammatory mediators and the inhibition of key proteins and enzymes in glucose and lipid metabolism.

Characterization of Chromatin Accessibility in Fetal Bovine Chondrocytes.

Despite significant advances of the bovine epigenome investigation, new evidence for the epigenetic basis of fetal cartilage development remains lacking. In this study, the chondrocytes were isolated from long bone tissues of bovine fetuses at 90 days. The Assay for Transposase-Accessible Chromatin with high throughput sequencing (ATAC-seq) and transcriptome sequencing (RNA-seq) were used to characterize gene expression and chromatin accessibility profile in bovine chondrocytes. A total of 9686 open chromatin regions in bovine fetal chondrocytes were identified and 45% of the peaks were enriched in the promoter regions. Then, all peaks were annotated to the nearest gene for Gene Ontology (GO) and Kyoto Encylopaedia of Genes and Genomes (KEGG) analysis. Growth and development-related processes such as amide biosynthesis process (GO: 0043604) and translation regulation (GO: 006417) were enriched in the GO analysis. The KEGG analysis enriched endoplasmic reticulum protein processing signal pathway, TGF-ß signaling pathway and cell cycle pathway, which are closely related to protein synthesis and processing during cell proliferation. Active transcription factors (TFs) were enriched by ATAC-seq, and were fully verified with gene expression levels obtained by RNA-seq. Among the top50 TFs from footprint analysis, known or potential cartilage development-related transcription factors FOS, FOSL2 and NFY were found. Overall, our data provide a theoretical basis for further determining the regulatory mechanism of cartilage development in bovine.

Evaluation of Linear Programming and Optimal Contribution Selection Approaches for Long-Term Selection on Beef Cattle Breeding.

The optimized selection method can maximize the genetic gain in offspring under the premise of controlling the inbreeding level of the population. At present, genetic gain has been largely improved by using genomic selection in multiple farm animals. However, the design of the optimal selection method and assessment of its effects during long-term selection in beef cattle breeding are yet to be fully explored. In this study, a simulated beef cattle population was constructed, and 15 generations of simulated breeding were carried out using the linear programming breeding strategy (LP) and optimal contribution selection strategy (OCS), respectively. The truncation selection strategy (TS-I and TS-II) was used as the control. During the breeding process, genetic parameters including genetic gain, average kinship coefficient, QTL effect variance, and average observed heterozygosity were calculated and compared across generations. Our results showed that the LP method can significantly improve the genetic gain in the population, especially the genetic performance of the traits with high heritability and the traits with high weight in the breeding process, but the inbreeding level of the population is higher under LP strategy. Although the genetic gain in the population under the OCS strategy is lower than the TS-II strategy, this method can effectively control the inbreeding level of the population. Our findings also suggest that the LP and OCS method can be used as an effective means to improve genetic gain, while the OCS method is a more ideal method to obtain sustainable genetic gain during long-term selection.

Environmental Stability and Transmissibility of Enveloped Viruses at Varied Animate and Inanimate Interfaces.

Enveloped viruses have been the leading causative agents of viral epidemics in the past decade, including the ongoing coronavirus disease 2019 outbreak. In epidemics caused by enveloped viruses, direct contact is a common route of infection, while indirect transmissions through the environment also contribute to the spread of the disease, although their significance remains controversial. Bridging the knowledge gap regarding the influence of interfacial interactions on the persistence of enveloped viruses in the environment reveals the transmission mechanisms when the virus undergoes mutations and prevents excessive disinfection during viral epidemics. Herein, from the perspective of the driving force, partition efficiency, and viral survivability at interfaces, we summarize the viral and environmental characteristics that affect the environmental transmission of viruses. We expect to provide insights for virus detection, environmental surveillance, and disinfection to limit the spread of severe acute respiratory syndrome coronavirus 2.

The eQTL colocalization and transcriptome-wide association study identify potentially causal genes responsible for economic traits in Simmental beef cattle.

BACKGROUND: A detailed understanding of genetic variants that affect beef merit helps maximize the efficiency of breeding for improved production merit in beef cattle. To prioritize the putative variants and genes, we ran a comprehensive genome-wide association studies (GWAS) analysis for 21 agronomic traits using imputed whole-genome variants in Simmental beef cattle. Then, we applied expression quantitative trait loci (eQTL) mapping between the genotype variants and transcriptome of three tissues (longissimus dorsi muscle, backfat, and liver) in 120 cattle. RESULTS: We identified 1,580 association signals for 21 beef agronomic traits using GWAS. We then illuminated 854,498 cis-eQTLs for 6,017 genes and 46,970 trans-eQTLs for 1,903 genes in three tissues and built a synergistic network by integrating transcriptomics with agronomic traits. These cis-eQTLs were preferentially close to the transcription start site and enriched in functional regulatory regions. We observed an average of 43.5% improvement in cis-eQTL discovery using multi-tissue eQTL mapping. Fine-mapping analysis revealed that 111, 192, and 194 variants were most likely to be causative to regulate gene expression in backfat, liver, and muscle, respectively. The transcriptome-wide association studies identified 722 genes significantly associated with 11 agronomic traits. Via the colocalization and Mendelian randomization analyses, we found that eQTLs of several genes were associated with the GWAS signals of agronomic traits in three tissues, which included genes, such as NADSYN1, NDUFS3, LTF and KIFC2 in liver, GRAMD1C, TMTC2 and ZNF613 in backfat, as well as TIGAR, NDUFS3 and L3HYPDH in muscle that could serve as the candidate genes for economic traits. CONCLUSIONS: The extensive atlas of GWAS, eQTL, fine-mapping, and transcriptome-wide association studies aid in the suggestion of potentially functional variants and genes in cattle agronomic traits and will be an invaluable source for genomics and breeding in beef cattle.

Disposable Polypropylene Face Masks: A Potential Source of Micro/Nanoparticles and Organic Contaminates in Humans.

We have been effectively protected by disposable propylene face masks during the COVID-19 pandemic; however, they may pose health risks due to the release of fine particles and chemicals. We measured micro/nanoparticles and organic chemicals in disposable medical masks, surgical masks, and (K)N95 respirators. In the breathing-simulation experiment, no notable differences were found in the total number of particles among mask types or between breathing intensities. However, when considering subranges, <2.5 µm particles accounted for ∼90% of the total number of micro/nanoparticles. GC-HRMS-based suspect screening tentatively revealed 79 (semi)volatile organic compounds in masks, with 18 being detected in ≥80% of samples and 44 in ≤20% of samples. Three synthetic phenolic antioxidants were quantified, and AO168 reached a median concentration of 2968 ng/g. By screening particles collected from bulk mask fabrics, we detected 18 chemicals, including four commonly detected in masks, suggesting chemical partition between the particles and the fabric fibers and chemical exposure via particle inhalation. These particles and chemicals are believed to originate from raw materials, intentionally and nonintentionally added substances in mask production, and their transformation products. This study highlights the need to study the long-term health risks associated with mask wearing and raises concerns over mask quality control.

MAK: a machine learning framework improved genomic prediction via multi-target ensemble regressor chains and automatic selection of assistant traits.

Incorporating the genotypic and phenotypic of the correlated traits into the multi-trait model can significantly improve the prediction accuracy of the target trait in animal and plant breeding, as well as human genetics. However, in most cases, the phenotypic information of the correlated and target trait of the individual to be evaluated was null simultaneously, particularly for the newborn. Therefore, we propose a machine learning framework, MAK, to improve the prediction accuracy of the target trait by constructing the multi-target ensemble regression chains and selecting the assistant trait automatically, which predicted the genomic estimated breeding values of the target trait using genotypic information only. The prediction ability of MAK was significantly more robust than the genomic best linear unbiased prediction, BayesB, BayesRR and the multi trait Bayesian method in the four real animal and plant datasets, and the computational efficiency of MAK was roughly 100 times faster than BayesB and BayesRR.

Genomic prediction of carcass traits using different haplotype block partitioning methods in beef cattle.

Genomic prediction (GP) based on haplotype alleles can capture quantitative trait loci (QTL) effects and increase predictive ability because the haplotypes are expected to be in linkage disequilibrium (LD) with QTL. In this study, we constructed haploblocks using LD-based and the fixed number of single nucleotide polymorphisms (fixed-SNP) methods with Illumina BovineHD chip in beef cattle. To evaluate the performance of different haplotype block partitioning methods, we constructed haploblocks based on LD thresholds (from r 2 > 0.2 to r 2 > 0.8) and the number of fixed-SNPs (5, 10, 20). The performance of predictive methods for three carcass traits including liveweight (LW), dressing percentage (DP), and longissimus dorsi muscle weight (LDMW) was evaluated using three approaches (GBLUP and BayesB model based on the SNP, GHBLUP, and BayesBH models based on the haploblock, and GHBLUP+GBLUP and BayesBH+BayesB models based on the combined haploblock and the nonblocked SNPs, which were located between blocks). In this study, we found the accuracies of LD-based and fixed-SNP haplotype Bayesian methods outperformed the Bayesian models (up to 8.54 ± 7.44% and 5.74 ± 2.95%, respectively). GHBLUP showed a high improvement (up to 11.29 ± 9.87%) compared with GBLUP. The Bayesian models have higher accuracies than BLUP models in most scenarios. The average computing time of the BayesBH+BayesB model can reduce by 29.3% compared with the BayesB model. The prediction accuracies using the LD-based haplotype method showed higher improvements than the fixed-SNP haplotype method. In addition, to avoid the influence of rare haplotypes generated from haplotype construction, we compared the performance of GP by filtering four types of minor haplotype allele frequency (MHAF) (0.01, 0.025, 0.05, and 0.1) under different conditions (LD levels were set at r 2 > 0.3, and the fixed number of SNPs was 5). We found the optimal MHAF threshold for LW was 0.01, and the optimal MHAF threshold for DP and LDMW was 0.025.

Cis-eQTL Analysis and Functional Validation of Candidate Genes for Carcass Yield Traits in Beef Cattle.

Carcass yield traits are of considerable economic importance for farm animals, which act as a major contributor to the world's food supply. Genome-wide association studies (GWASs) have identified many genetic variants associated with carcass yield traits in beef cattle. However, their functions are not effectively illustrated. In this study, we performed an integrative analysis of gene-based GWAS with expression quantitative trait locus (eQTL) analysis to detect candidate genes for carcass yield traits and validate their effects on bovine skeletal muscle satellite cells (BSCs). The gene-based GWAS and cis-eQTL analysis revealed 1780 GWAS and 1538 cis-expression genes. Among them, we identified 153 shared genes that may play important roles in carcass yield traits. Notably, the identified cis-eQTLs of PON3 and PRIM2 were significantly (p < 0.001) enriched in previous GWAS loci for carcass traits. Furthermore, overexpression of PON3 and PRIM2 promoted the BSCs' proliferation, increased the expression of MYOD and downregulated the expression of MYOG, which indicated that these genes may inhibit myogenic differentiation. In contrast, PON3 and PRIM2 were significantly downregulated during the differentiation of BSCs. These findings suggested that PON3 and PRIM2 may promote the proliferation of BSCs and inhibit them in the pre-differentiation stage. Our results further contribute to the understanding of the molecular mechanisms of carcass yield traits in beef cattle.

Improving Genomic Prediction with Machine Learning Incorporating TPE for Hyperparameters Optimization.

Depending on excellent prediction ability, machine learning has been considered the most powerful implement to analyze high-throughput sequencing genome data. However, the sophisticated process of tuning hyperparameters tremendously impedes the wider application of machine learning in animal and plant breeding programs. Therefore, we integrated an automatic tuning hyperparameters algorithm, tree-structured Parzen estimator (TPE), with machine learning to simplify the process of using machine learning for genomic prediction. In this study, we applied TPE to optimize the hyperparameters of Kernel ridge regression (KRR) and support vector regression (SVR). To evaluate the performance of TPE, we compared the prediction accuracy of KRR-TPE and SVR-TPE with the genomic best linear unbiased prediction (GBLUP) and KRR-RS, KRR-Grid, SVR-RS, and SVR-Grid, which tuned the hyperparameters of KRR and SVR by using random search (RS) and grid search (Gird) in a simulation dataset and the real datasets. The results indicated that KRR-TPE achieved the most powerful prediction ability considering all populations and was the most convenient. Especially for the Chinese Simmental beef cattle and Loblolly pine populations, the prediction accuracy of KRR-TPE had an 8.73% and 6.08% average improvement compared with GBLUP, respectively. Our study will greatly promote the application of machine learning in GP and further accelerate breeding progress.

Incorporating kernelized multi-omics data improves the accuracy of genomic prediction.

BACKGROUND: Genomic selection (GS) has revolutionized animal and plant breeding after the first implementation via early selection before measuring phenotypes. Besides genome, transcriptome and metabolome information are increasingly considered new sources for GS. Difficulties in building the model with multi-omics data for GS and the limit of specimen availability have both delayed the progress of investigating multi-omics. RESULTS: We utilized the Cosine kernel to map genomic and transcriptomic data as [Formula: see text] symmetric matrix (G matrix and T matrix), combined with the best linear unbiased prediction (BLUP) for GS. Here, we defined five kernel-based prediction models: genomic BLUP (GBLUP), transcriptome-BLUP (TBLUP), multi-omics BLUP (MBLUP, [Formula: see text]), multi-omics single-step BLUP (mssBLUP), and weighted multi-omics single-step BLUP (wmssBLUP) to integrate transcribed individuals and genotyped resource population. The predictive accuracy evaluations in four traits of the Chinese Simmental beef cattle population showed that (1) MBLUP was far preferred to GBLUP (ratio = 1.0), (2) the prediction accuracy of wmssBLUP and mssBLUP had 4.18% and 3.37% average improvement over GBLUP, (3) We also found the accuracy of wmssBLUP increased with the growing proportion of transcribed cattle in the whole resource population. CONCLUSIONS: We concluded that the inclusion of transcriptome data in GS had the potential to improve accuracy. Moreover, wmssBLUP is accepted to be a promising alternative for the present situation in which plenty of individuals are genotyped when fewer are transcribed.