Identifying SARS-CoV-2 Lineage Mutation Hallmarks and Correlating Them With Clinical Outcomes in Egypt: A Pilot Study.

The SARS-CoV-2 pandemic has led to over 4.9 million deaths as of October 2021. One of the main challenges of creating vaccines, treatment, or diagnostic tools for the virus is its mutations and emerging variants. A couple of variants were declared as more virulent and infectious than others. Some approaches were used as nomenclature for SARS-CoV-2 variants and lineages. One of the most used is the Pangolin nomenclature. In our study, we enrolled 35 confirmed SARS-CoV-2 patients and sequenced the viral RNA in their samples. We also aimed to highlight the hallmark mutations in the most frequent lineage. We identified a seven-mutation signature for the SARS-CoV-2 C36 lineage, detected in 56 countries and an emerging lineage in Egypt. In addition, we identified one mutation which was highly negatively correlated with the lineage. On the other hand, we found no significant correlation between our clinical outcomes and the C36 lineage. In conclusion, the C36 lineage is an emerging SARS-CoV-2 variant that needs more investigation regarding its clinical outcomes compared to other strains. Our study paves the way for easier diagnosis of variants of concern using mutation signatures.

ABHD4-Regulating RNA Panel: Novel Biomarkers in Acute Coronary Syndrome Diagnosis.

BACKGROUND: Acute coronary syndrome (ACS) is a major cause of death all over the world. STEMI represents a type of myocardial infarction with acute ST elevation. We aimed to assess the predictive power of potential RNA panel expression in acute coronary syndrome. METHOD: We used in silico data analysis to retrieve RNAs related to glycerophospholipid metabolism dysregulation and specific to ACS that results in the selection of Alpha/Beta hydrolase fold domain4 (ABHD4) mRNA and its epigenetic regulators (Foxf1 adjacent noncoding developmental regulatory RNA (FENDRR) lncRNA, miRNA-221, and miRNA-197). We assessed the expression of the serum RNA panel in 68 patients with ACS, 21 patients with chest pain due to non-cardiac causes, and 21 healthy volunteers by quantitative real-time polymerase chain reaction. RESULTS: The study data showed significant down regulation in the expression of the serum levels of FENDRR lncRNA and miRNA-221-3p by 120-fold and 22-fold in Unstable angina (UA) in comparison with healthy volunteers, and by 8.6-fold and 2-fold in ST segment elevation myocardial infarction (STEMI) patients versus UA; concomitant upregulation in the expression of ABHD4 mRNA and miRNA-197-5p by 444-fold and 10-fold in UA compared with healthy volunteers, and by 1.54-fold and 4.5-fold in STEMI versus unstable angina. Performance characteristics analysis showed that the ABHD4-regulating RNA panel were potential biomarkers for prediction of ACS. Moreover, there was a significant association between the 2 miRNAs and ABHD4 mRNA and the regulating FENDRR lncRNA. CONCLUSION: Collectively, ABHD4 mRNA regulating RNA panel based on putative interactions seems to be novel non-invasive biomarkers that could detect ACS early and stratify severity of the condition that could improve health outcome.

lncRNA- RP11-156p1.3, novel diagnostic and therapeutic targeting via CRISPR/Cas9 editing in hepatocellular carcinoma.

We aim to characterize the expression of RNA panel in HCC. We assessed the expression of HCC-associated mRNA, miRNA and lncRNA network by real time PCR in sera and tissue samples. In a proof-of-principle approach, CRISPR cas9 mediated knock out for lncRNA- RP11-156p1.3 was performed in HEPG2 cell line to validate the role of the chosen RNA in HCC pathogenesis. The differential expression of RFTN1 mRNA, lncRNA- RP11-156p1.3 and miRNA-4764-5p was statistically different among the studied groups. After CRISPR cas9 mediated knockout of lncRNA- RP11-156p1.3 in HEPG2 cells, there was significant decrease in cell count and viability with reversal of the expression of the chosen RNAs. The chosen RNAs play a significant role in HCC pathogenesis and may be potential diagnostic and therapeutic targets.