Recent Update of COVID-19 Vaccines.

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) has been recently identified as a novel member of beta coronaviruses (CoVs) and the cause of coronavirus disease 2019 (COVID-19). It has been first discovered in China and soon has spread across continents with an escalating number of mortalities. There is an urgent need for developing a COVID-19 vaccine to control the rapid transmission and the deleterious impact of the virus. The potent vaccine should have a good tolerable and efficacious profile to induce target-specific humoral and cellular immune responses. It should also exhibit no or minimal detrimental effects in children, young adults, and elderly people with or without co-morbidities from different racial backgrounds. Previously published findings of SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV) played vital role in the characterization of surface spike proteins as the tool of entry of the SARS-CoV-2 into host cells. It has become evident that SARS-CoVs have high genetic similarity and this implies antecedent vaccination strategies could be implicated in the production of COVID-19 vaccines. Although several vaccines have been approved and rolled out, only a handful of them have passed the three phases of clinical studies. This review highlights the completed, and ongoing clinical trials of COVID-19 vaccines and efforts are being made globally to avert the pandemic.

Urgent need for consistent standards in functional enrichment analysis.

Gene set enrichment tests (a.k.a. functional enrichment analysis) are among the most frequently used methods in computational biology. Despite this popularity, there are concerns that these methods are being applied incorrectly and the results of some peer-reviewed publications are unreliable. These problems include the use of inappropriate background gene lists, lack of false discovery rate correction and lack of methodological detail. To ascertain the frequency of these issues in the literature, we performed a screen of 186 open-access research articles describing functional enrichment results. We find that 95% of analyses using over-representation tests did not implement an appropriate background gene list or did not describe this in the methods. Failure to perform p-value correction for multiple tests was identified in 43% of analyses. Many studies lacked detail in the methods section about the tools and gene sets used. An extension of this survey showed that these problems are not associated with journal or article level bibliometrics. Using seven independent RNA-seq datasets, we show misuse of enrichment tools alters results substantially. In conclusion, most published functional enrichment studies suffered from one or more major flaws, highlighting the need for stronger standards for enrichment analysis.

Sex-Based Mhrt Methylation Chromatinizes MeCP2 in the Heart.

In the heart, primary microRNA-208b (pri-miR-208b) and Myheart (Mhrt) are long non-coding RNAs (lncRNAs) encoded by the cardiac myosin heavy chain genes. Although preclinical studies have shown that lncRNAs regulate gene expression and are protective for pathological hypertrophy, the mechanism underlying sex-based differences remains poorly understood. In this study, we examined DNA- and RNA-methylation-dependent regulation of pri-miR-208b and Mhrt. Expression of pri-miR-208b is elevated in the left ventricle of the female heart. Despite indistinguishable DNA methylation between sexes, the interaction of MeCP2 on chromatin is subject to RNase digestion, highlighting that affinity of the methyl-CG reader is broader than previously thought. A specialized procedure to isolate RNA from soluble cardiac chromatin emphasizes sex-based affinity of an MeCP2 co-repressor complex with Rest and Hdac2. Sex-specific Mhrt methylation chromatinizes MeCP2 at the pri-miR-208b promoter and extends the functional relevance of default transcriptional suppression in the heart.