ENet-6mA: Identification of 6mA Modification Sites in Plant Genomes Using ElasticNet and Neural Networks

N6-methyladenine (6mA) has been recognized as a key epigenetic alteration that affects a variety of biological activities. Precise prediction of 6mA modification sites is essential for understanding the logical consistency of biological activity. There are various experimental methods for identifying 6mA modification sites, but in silico prediction has emerged as a potential option due to the very high cost and labor-intensive nature of experimental procedures. Taking this into consideration, developing an efficient and accurate model for identifying N6-methyladenine is one of the top objectives in the field of bioinformatics. Therefore, we have created an in silico model for the classification of 6mA modifications in plant genomes. ENet-6mA uses three encoding methods, including one-hot, nucleotide chemical properties (NCP), and electron–ion interaction potential (EIIP), which are concatenated and fed as input to ElasticNet for feature reduction, and then the optimized features are given directly to the neural network to get classified. We used a benchmark dataset of rice for five-fold cross-validation testing and three other datasets from plant genomes for cross-species testing purposes. The results show that the model can predict the N6-methyladenine sites very well, even cross-species. Additionally, we separated the datasets into different ratios and calculated the performance using the area under the precision–recall curve (AUPRC), achieving 0.81, 0.79, and 0.50 with 1:10 (positive:negative) samples for F. vesca, R. chinensis, and A. thaliana, respectively.     

Experiences of Trauma and DNA Methylation Profiles among African American Mothers and Children

Potentially traumatic experiences have been associated with chronic diseases. Epigenetic mechanisms, including DNA methylation (DNAm), have been proposed as an explanation for this association. We examined the association of experiences of trauma with epigenome-wide DNAm among African American mothers (n = 236) and their children aged 3–5 years (n = 232; N = 500), using the Life Events Checklist-5 (LEC) and Traumatic Events Screening Inventory—Parent Report Revised (TESI-PRR). We identified no DNAm sites significantly associated with potentially traumatic experience scores in mothers. One CpG site on the ENOX1 gene was methylome-wide-significant in children (FDR-corrected q-value = 0.05) from the TESI-PRR. This protein-coding gene is associated with mental illness, including unipolar depression, bipolar, and schizophrenia. Future research should further examine the associations between childhood trauma, DNAm, and health outcomes among this understudied and high-risk group. Findings from such longitudinal research may inform clinical and translational approaches to prevent adverse health outcomes associated with epigenetic changes.     

Challenges in Understanding Genome-Wide DNA Methylation

DNA methylation is a chemical modification of the bases in genomes. This modification, most frequently found at CpG dinucleotides in eukaryotes, has been identified as having multiple critical functions in broad and diverse species of animals and plants, while mysteriously appears to be lacking from several other well-studied species. DNA methylation has well known and important roles in genome stability and defense, its pattern change highly correlates with gene regulation. Much evidence has linked abnorma...     

Clinical Relevance of CDH1 and CDH13 DNA-Methylation in Serum of Cervical Cancer Patients

This study was designed to investigate the DNA-methylation status of E-cadherin (CDH1) and H-cadherin (CDH13) in serum samples of cervical cancer patients and control patients with no malignant diseases and to evaluate the clinical utility of these markers. DNA-methylation status of CDH1 and CDH13 was analyzed by means of MethyLight-technology in serum samples from 49 cervical cancer patients and 40 patients with diseases other than cancer. To compare this methylation analysis with another technique, we analyzed the samples with a denaturing high performance liquid chromatography (DHPLC) PCR-method. The specificity and sensitivity of CDH1 DNA-methylation measured by MethyLight was 75% and 55%, and for CDH13 DNA-methylation 95% and 10%. We identified a specificity of 92.5% and a sensitivity of only 27% for the CDH1 DHPLC-PCR analysis. Multivariate analysis showed that serum CDH1 methylation-positive patients had a 7.8-fold risk for death (95% CI: 2.2-27.7; p = 0.001) and a 92.8-fold risk for relapse (95% CI: 3.9-2207.1; p = 0.005). We concluded that the serological detection of CDH1 and CDH13 DNA-hypermethylation is not an ideal diagnostic tool due to low diagnostic specificity and sensitivity. However, it was validated that CDH1 methylation analysis in serum samples may be of potential use as a prognostic marker for cervical cancer patients.     

Dysregulated MicroRNAs as Biomarkers or Therapeutic Targets in Cisplatin-Induced Nephrotoxicity: A Systematic Review

The purpose of this systematic review was to map out and summarize scientific evidence on dysregulated microRNAs (miRNAs) that can be possible biomarkers or therapeutic targets for cisplatin nephrotoxicity and have already been tested in humans, animals, or cells. In addition, an in silico analysis of the two miRNAs found to be dysregulated in the majority of studies was performed. A literature search was performed using eight databases for studies published up to 4 July 2021. Two independent reviewers selected the studies and extracted the data; disagreements were resolved by a third and fourth reviewers. A total of 1002 records were identified, of which 30 met the eligibility criteria. All studies were published in English and reported between 2010 and 2021. The main findings were as follows: (a) miR-34a and miR-21 were the main miRNAs identified by the studies as possible biomarkers and therapeutic targets of cisplatin nephrotoxicity; (b) the in silico analysis revealed 124 and 131 different strongly validated targets for miR-34a and miR-21, respectively; and (c) studies in humans remain scarce.     

The Acid/Base Characterization of Molecules with Epigenetic Activity

The acidic and basic functional groups in a molecule strongly influence its physicochemical properties, affinity for a macromolecule, pharmacokinetics, and toxicity. For instance, basicity has been correlated with molecular promiscuity, hERG blockade, and phospholipidosis. Nonetheless, no systematic characterization of the acid/base profile of epigenomic databases has been reported. This study describes an analysis of the acidic ionization constant distribution of a library of 7820 compounds with reported activity against epigenetic targets. Furthermore, the epigenomics database's acid/base profile was compared to the reference libraries of food chemicals, natural products, and approved drugs. It was found that the acid/base profile of histone lysine demethylase ligands is more similar to previously approved drugs, and histone acetyltransferase ligands have acidic and basic functional groups largely found in food chemicals and natural products; this support the potential of these libraries for finding new epigenetic inhibitors.     

Molecular Mechanisms of Cutaneous Inflammatory Disorder: Atopic Dermatitis

Atopic dermatitis (AD) is a multifactorial inflammatory skin disease resulting from interactions between genetic susceptibility and environmental factors. The pathogenesis of AD is poorly understood, and the treatment of recalcitrant AD is still challenging. There is accumulating evidence for new gene polymorphisms related to the epidermal barrier function and innate and adaptive immunity in patients with AD. Newly-found T cells and dendritic cell subsets, cytokines, chemokines and signaling pathways have extended our understanding of the molecular pathomechanism underlying AD. Genetic changes caused by environmental factors have been shown to contribute to the pathogenesis of AD. We herein present a review of the genetics, epigenetics, barrier dysfunction and immunological abnormalities in AD with a focus on updated molecular biology.     

Genomics and Epigenomics in the Molecular Biology of Melanoma—A Prerequisite for Biomarkers Studies

Melanoma is a common and aggressive tumor originating from melanocytes. The increasing incidence of cutaneous melanoma in recent last decades highlights the need for predictive biomarkers studies. Melanoma development is a complex process, involving the interplay of genetic, epigenetic, and environmental factors. Genetic aberrations include BRAF, NRAS, NF1, MAP2K1/MAP2K2, KIT, GNAQ, GNA11, CDKN2A, TERT mutations, and translocations of kinases. Epigenetic alterations involve microRNAs, non-coding RNAs, histones modifications, and abnormal DNA methylations. Genetic aberrations and epigenetic marks are important as biomarkers for the diagnosis, prognosis, and prediction of disease recurrence, and for therapeutic targets. This review summarizes our current knowledge of the genomic and epigenetic changes in melanoma and discusses the latest scientific information.