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

Diniz, Wellison J. S.; Banerjee, Priyanka; Rodning, Soren P.; Dyce, Paul W.

doi:10.3390/ani12192715

Cited by 6 publications

(6 citation statements)

References 64 publications

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“…indicator of pregnancy status in cows, and a link between FNDC1 and the reproductive process was also demonstrated [69]. MSTRG.160,822 was predicted to be a cisacting element of FNDC1, regulating its expression.…”

Section: Discussionmentioning

confidence: 92%

Key mRNAs and lncRNAs of pituitary that affect the reproduction of FecB + + small tail han sheep

Yang,

Tang,

et al. 2024

BMC Genomics

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Background The pituitary directly regulates the reproductive process through follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Transcriptomic research on the pituitaries of ewes with different FecB (fecundity Booroola) genotypes has shown that some key genes and lncRNAs play an important role in pituitary function and sheep fecundity. Our previous study found that ewes with FecB + + genotypes (without FecB mutation) still had individuals with more than one offspring per birth. It is hoped to analyze this phenomenon from the perspective of the pituitary transcriptome. Results The 12 Small Tail Han Sheep were equally divided into polytocous sheep in the follicular phase (PF), polytocous sheep in the luteal phase (PL), monotocous sheep in the follicular phase (MF), and monotocous sheep in the luteal phase (ML). Pituitary tissues were collected after estrus synchronous treatment for transcriptomic analysis. A total of 384 differentially expressed genes (DEGs) (182 in PF vs. MF and 202 in PL vs. ML) and 844 differentially expressed lncRNAs (DELs) (427 in PF vs. MF and 417 in PL vs. ML) were obtained from the polytocous-monotocous comparison groups in the two phases. Functional enrichment analysis showed that the DEGs in the two phases were enriched in signaling pathways known to play an important role in sheep fecundity, such as calcium ion binding and cAMP signaling pathways. A total of 1322 target relationship pairs (551 pairs in PF vs. MF and 771 pairs in PL vs. ML) were obtained for the target genes prediction of DELs, of which 29 DEL-DEG target relationship pairs (nine pairs in PF vs. MF and twenty pairs in PL vs. ML). In addition, the competing endogenous RNA (ceRNA) networks were constructed to explore the regulatory relationships of DEGs, and some important regulatory relationship pairs were obtained. Conclusion According to the analysis results, we hypothesized that the pituitary first receives steroid hormone signals from the ovary and uterus and that VAV3 (Vav Guanine Nucleotide Exchange Factor 3), GABRG1 (Gamma-Aminobutyric Acid A Receptor, Gamma 1), and FNDC1 (Fibronectin Type III Domain Containing 1) played an important role in this process. Subsequently, the reproductive process was regulated by gonadotropins, and IGFBP1 (Insulin-like Growth Factor Binding Protein 1) was directly involved in this process, ultimately affecting litter size. In addition, TGIF1 (Transforming Growth Factor-Beta-Induced Factor 1) and TMEFF2 (Transmembrane Protein With EGF Like And Two Follistatin Like Domains 2) compensated for the effect of the FecB mutation and function by acting on TGF-β/SMAD signaling pathway, an important pathway for sheep reproduction. These results provided a reference for understanding the mechanism of multiple births in Small Tail Han Sheep without FecB mutation.

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Section: Discussionmentioning

confidence: 92%

Key mRNAs and lncRNAs of pituitary that affect the reproduction of FecB + + small tail han sheep

Yang,

Tang,

et al. 2024

BMC Genomics

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“…Further details on the experimental design and procedures were described elsewhere [14]. The data were downloaded from the GEO database using the SRA-Explorer web tool v.1.0 [20] and processed using a custom-built bioinformatics pipeline, as previously described [21]. First, FastQC v0.11.9 [22] and MultiQC v1.11 [23] software were used for the quality control (QC) and aggregation of results, respectively.…”

Section: Methodsmentioning

confidence: 99%

Mapping Expression Quantitative Trait Loci Targeting Candidate Genes for Pregnancy in Beef Cows

Diniz,

Afonso,

Kertz

et al. 2024

Biomolecules

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Despite collective efforts to understand the complex regulation of reproductive traits, no causative genes and/or mutations have been reported yet. By integrating genomics and transcriptomics data, potential regulatory mechanisms may be unveiled, providing opportunities to dissect the genetic factors governing fertility. Herein, we identified regulatory variants from RNA-Seq data associated with gene expression regulation in the uterine luminal epithelial cells of beef cows. We identified 4676 cis and 7682 trans eQTLs (expression quantitative trait loci) affecting the expression of 1120 and 2503 genes, respectively (FDR < 0.05). These variants affected the expression of transcription factor coding genes (71 cis and 193 trans eQTLs) and genes previously reported as differentially expressed between pregnant and nonpregnant cows. Functional over-representation analysis highlighted pathways related to metabolism, immune response, and hormone signaling (estrogen and GnRH) affected by eQTL-regulated genes (p-value ≤ 0.01). Furthermore, eQTLs were enriched in QTL regions for 13 reproduction-related traits from the CattleQTLdb (FDR ≤ 0.05). Our study provides novel insights into the genetic basis of reproductive processes in cattle. The underlying causal mechanisms modulating the expression of uterine genes warrant further investigation.

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“…Similarly, multi-omics data integration will allow us to discover and prioritize candidate markers. Preliminary work from our group on machine learning and network modeling has provided a framework for prioritizing genes for fertility [28]. Approaches integrating transcriptomics into proteomics or metabolomics to identify candidates for early pregnancy diagnosis or fertility, respectively, have been described [81,115].…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

“…Although promising, findings from different research groups around the globe are still limited, as no major genes or genetic variants regulating fertility have been reported. Other omics-based approaches have increasingly been used to dissect the molecular basis of fertility and provide a more comprehensive understanding of the biological pathways associated with reproductive success [25][26][27][28][29]. Advances in metabolomics and proteomics applications in relation to cow fertility were discussed by Aranciaga et al [30].…”

Section: Introductionmentioning

confidence: 99%

Harnessing Genomics and Transcriptomics Approaches to Improve Female Fertility in Beef Cattle—A Review

Kertz,

Banerjee,

Dyce

et al. 2023

Animals

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Female fertility is the foundation of the cow–calf industry, impacting both efficiency and profitability. Reproductive failure is the primary reason why beef cows are sold in the U.S. and the cause of an estimated annual gross loss of USD 2.8 billion. In this review, we discuss the status of the genomics, transcriptomics, and systems genomics approaches currently applied to female fertility and the tools available to cow–calf producers to maximize genetic progress. We highlight the opportunities and limitations associated with using genomic and transcriptomic approaches to discover genes and regulatory mechanisms related to beef fertility. Considering the complex nature of fertility, significant advances in precision breeding will rely on holistic, multidisciplinary approaches to further advance our ability to understand, predict, and improve reproductive performance. While these technologies have advanced our knowledge, the next step is to translate research findings from bench to on-farm applications.

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

Cited by 6 publications

References 64 publications

Key mRNAs and lncRNAs of pituitary that affect the reproduction of FecB + + small tail han sheep

Key mRNAs and lncRNAs of pituitary that affect the reproduction of FecB + + small tail han sheep

Mapping Expression Quantitative Trait Loci Targeting Candidate Genes for Pregnancy in Beef Cows

Harnessing Genomics and Transcriptomics Approaches to Improve Female Fertility in Beef Cattle—A Review

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