The horse reference genome assemblies, EquCab2.0 and EquCab3.0, have enabled great advancements in the equine genomics field, from tools to novel discoveries. However, significant gaps of knowledge regarding genome function remain, hindering the study of complex traits in horses. In an effort to address these gaps and with inspiration from the Encyclopedia of DNA Elements (ENCODE) project, the equine Functional Annotation of Animal Genome (FAANG) initiative was proposed to bridge the gap between genome and gene expression, providing further insights into functional regulation within the horse genome. Three years after launching the initiative, the equine FAANG group has generated data from more than 400 experiments using over 50 tissues, targeting a variety of regulatory features of the equine genome. In this review, we examine how valuable lessons learned from the ENCODE project informed our decisions in the equine FAANG project. We report the current state of the equine FAANG project and discuss how FAANG can serve as a template for future expansion of functional annotation in the equine genome and be used as a reference for studies of complex traits in horse. A well-annotated reference functional atlas will also help advance equine genetics in the pan-genome and precision medicine era.

Decoding the Equine Genome: Lessons from ENCODE.

A high-quality reference genome assembly, a biobank of diverse equine tissues from the Functional Annotation of the Animal Genome (FAANG) initiative, and incorporation of long-read sequencing technologies, have enabled efforts to build a comprehensive and tissue-specific equine transcriptome. The equine FAANG transcriptome reported here provides up to 45% improvement in transcriptome completeness across tissue types when compared to either RefSeq or Ensembl transcriptomes. This transcriptome also provides major improvements in the identification of alternatively spliced isoforms, novel noncoding genes, and 3’ transcription termination site (TTS) annotations. The equine FAANG transcriptome will empower future functional studies of important equine traits while providing future opportunities to identify allele-specific expression and differentially expressed genes across tissues.

https://www.biorxiv.org/content/biorxiv/early/2022/06/09/2022.06.07.495038.full.pdf

Long-read RNA Sequencing Improves the Annotation of the Equine Transcriptome

Enhancer RNAs (eRNAs), a class of non-coding RNAs (ncRNAs) transcribed from enhancer regions, serve as a type of critical regulatory element in gene expression. There is increasing evidence demonstrating that the aberrant expression of eRNAs can be broadly detected in various human diseases. Some studies also revealed the potential clinical utility of eRNAs in these diseases. In this review, we summarized the recent studies regarding the pathological mechanisms of eRNAs as well as their potential utility across human diseases, including cancers, neurodegenerative disorders, cardiovascular diseases and metabolic diseases. It could help us to understand how eRNAs are engaged in the processes of diseases and to obtain better insight of eRNAs in diagnosis, prognosis or therapy. The studies we reviewed here indicate the enormous therapeutic potency of eRNAs across human diseases.

/pdf/enhancer-rna-erna-in-human-diseases-1encjp2p.pdf

Enhancer RNA (eRNA) in Human Diseases

Aim: To assess the serum levels of HSP70 concentrations in ectopic pregnancy (EP) patients compared with abortus imminens (AI) patients and healthy controls. Materials & methods: Age-matched patients were divided into three groups, with 30 patients in each group: EP, AI and healthy intrauterine pregnancy groups. Blood samples were taken from the antecubital vein and kept for HSP70 analysis. Results: The HSP70 levels were higher in the EP group than in AI patients and healthy controls (p < 0.05). The area under the curve for the serum HSP70 assay reached a value of 0.81 for a cutoff point of 11.12 pg/ml, which identified women with EP. Conclusion: Serum HSP70 levels increased in women with EP compared with healthy controls and women with AI.

Evaluation of HSP70 levels in ectopic pregnancy, abortus imminens and intrauterine pregnancy.

Enhancers are cis-acting elements that control the transcription of target genes and are transcribed into a class of noncoding RNAs (ncRNAs) termed enhancer RNAs (eRNAs). eRNAs have shorter half-lives than mRNAs and long noncoding RNAs; however, the frequency of transcription of eRNAs is close to that of mRNAs. eRNA expression is associated with a high level of histone mark H3K27ac and a low level of H3K27me3. Although eRNAs only account for a small proportion of ncRNAs, their functions are important. eRNAs can not only increase enhancer activity by promoting the formation of enhancer-promoter loops but also regulate transcriptional activation. Increasing numbers of studies have found that eRNAs play an important role in the occurrence and development of brain diseases; however, further research into eRNAs is required. This review discusses the concept, characteristics, classification, function, and potential roles of eRNAs in brain diseases.

Insights into Enhancer RNAs: Biogenesis and Emerging Role in Brain Diseases.

Abstract At present, the diagnosis of ectopic pregnancy mainly depends on transvaginal ultrasound and β-hCG. However, these methods may delay diagnosis and treatment time. Therefore, we aimed to screen for serological molecular markers for the early diagnosis of ectopic pregnancy (EP).Using data-independent acquisition (DIA)proteomics, the differential proteins in serum were selected between the intrauterine pregnancy (IP) and EP groups. Then, the expression levels of these differential proteins were measured by enzyme-linked immunosorbent assay. The diagnostic value of the serum biomarkers was evaluated by receiver operating characteristic curve analysis.GSTO1, ECM-1 and β-hCG showed significant differences between the EP and IP groups ( P &lt; 0.05). The combination of GSTO1/ECM-1/β-hCG had an area under the curve of 0.93 (95% CI 0.88–0.99), a sensitivity of 88.89% (95% CI 73.94–96.89) and a specificity of 86.11% (95% CI 70.50–95.33) with a likelihood ratio of 6.40.The combination of GSTO1/ECM-1/β-hCG may be developed into a possible approach for the early diagnosis of EP. 

/pdf/identification-of-noninvasive-diagnostic-biomarkers-for-2toguvh3.pdf

Yuxin Shen

Papers

Insights into Enhancer RNAs: Biogenesis and Emerging Role in Brain Diseases.

Identification of noninvasive diagnostic biomarkers for ectopic pregnancy using data-independent acquisition (DIA)proteomics: a pilot study