RESUMO
Coronavirus Disease 2019 (COVID-19), although most commonly demonstrates respiratory symptoms, but there is a growing set of evidence reporting its correlation with the digestive tract and faeces. Interestingly, recent studies have shown the association of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection with gastrointestinal symptoms in infected patients but any sign of respiratory issues. Moreover, some studies have also shown that the presence of live SARS-CoV-2 virus in the faeces of patients with COVID-19. Therefore, the pathophysiology of digestive symptoms associated with COVID-19 has raised a critical need for comprehensive investigative efforts. To address this issue we have developed a bioinformatics pipeline involving a system biological framework to identify the effects of SARS-CoV-2 messenger RNA expression on deciphering its association with digestive symptoms in COVID-19 positive patients. Using two RNA-seq datasets derived from COVID-19 positive patients with celiac (CEL), Crohn's (CRO) and ulcerative colitis (ULC) as digestive disorders, we have found a significant overlap between the sets of differentially expressed genes from SARS-CoV-2 exposed tissue and digestive tract disordered tissues, reporting 7, 22 and 13 such overlapping genes, respectively. Moreover, gene set enrichment analysis, comprehensive analyses of protein-protein interaction network, gene regulatory network, protein-chemical agent interaction network revealed some critical association between SARS-CoV-2 infection and the presence of digestive disorders. The infectome, diseasome and comorbidity analyses also discover the influences of the identified signature genes in other risk factors of SARS-CoV-2 infection to human health. We hope the findings from this pathogenetic analysis may reveal important insights in deciphering the complex interplay between COVID-19 and digestive disorders and underpins its significance in therapeutic development strategy to combat against COVID-19 pandemic.
Assuntos
Tratamento Farmacológico da COVID-19 , Trato Gastrointestinal/virologia , SARS-CoV-2/efeitos dos fármacos , COVID-19/virologia , Comorbidade , Biologia Computacional , Trato Gastrointestinal/patologia , Redes Reguladoras de Genes/genética , Humanos , Pandemias , Mapas de Interação de Proteínas/genética , SARS-CoV-2/patogenicidade , Biologia de SistemasRESUMO
Reproducibility of scientific results is a key element of science and credibility. The lack of reproducibility across many scientific fields has emerged as an important concern. In this piece, we assess mathematical model reproducibility and propose a scorecard for improving reproducibility in this field.
Assuntos
Biologia de Sistemas/métodos , Curadoria de Dados , Humanos , Modelos Teóricos , Reprodutibilidade dos TestesRESUMO
An outbreak, caused by an RNA virus, SARS-CoV-2 named COVID-19 has become pandemic with a magnitude which is daunting to all public health institutions in the absence of specific antiviral treatment. Surface glycoprotein and nucleocapsid phosphoprotein are two important proteins of this virus facilitating its entry into host cell and genome replication. Small interfering RNA (siRNA) is a prospective tool of the RNA interference (RNAi) pathway for the control of human viral infections by suppressing viral gene expression through hybridization and neutralization of target complementary mRNA. So, in this study, the power of RNA interference technology was harnessed to develop siRNA molecules against specific target genes namely, nucleocapsid phosphoprotein gene and surface glycoprotein gene. Conserved sequence from 139 SARS-CoV-2 strains from around the globe was collected to construct 78 siRNA that can inactivate nucleocapsid phosphoprotein and surface glycoprotein genes. Finally, based on GC content, free energy of folding, free energy of binding, melting temperature, efficacy prediction and molecular docking analysis, 8 siRNA molecules were selected which are proposed to exert the best action. These predicted siRNAs should effectively silence the genes of SARS-CoV-2 during siRNA mediated treatment assisting in the response against SARS-CoV-2.
Assuntos
COVID-19/terapia , Química Computacional , Proteínas do Nucleocapsídeo de Coronavírus/genética , Desenho de Fármacos , Terapia Genética/métodos , Simulação de Acoplamento Molecular , Interferência de RNA , RNA Mensageiro/antagonistas & inibidores , RNA Interferente Pequeno/química , RNA Viral/antagonistas & inibidores , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/genética , Proteínas Argonautas/química , Proteínas Argonautas/genética , Composição de Bases , COVID-19/virologia , Evolução Molecular , Regulação Viral da Expressão Gênica/efeitos dos fármacos , Humanos , Pandemias , Fosfoproteínas/genética , Filogenia , Dobramento de RNA , RNA Guia de Cinetoplastídeos/química , RNA Guia de Cinetoplastídeos/genética , RNA Mensageiro/genética , RNA Interferente Pequeno/farmacologia , RNA Interferente Pequeno/uso terapêutico , RNA Viral/genética , SARS-CoV-2/efeitos dos fármacos , Alinhamento de Sequência , Termodinâmica , Tratamento Farmacológico da COVID-19RESUMO
Esophageal carcinoma (ESCA) has a 5-year survival rate of fewer than 20%. The study aimed to identify new predictive biomarkers for ESCA through transcriptomics meta-analysis to address the problems of ineffective cancer therapy, lack of efficient diagnostic tools, and costly screening and contribute to developing more efficient cancer screening and treatments by identifying new marker genes. Nine GEO datasets of three kinds of esophageal carcinoma were analyzed, and 20 differentially expressed genes were detected in carcinogenic pathways. Network analysis revealed four hub genes, namely RAR Related Orphan Receptor A (RORA), lysine acetyltransferase 2B (KAT2B), Cell Division Cycle 25B (CDC25B), and Epithelial Cell Transforming 2 (ECT2). Overexpression of RORA, KAT2B, and ECT2 was identified with a bad prognosis. These hub genes modulate immune cell infiltration. These hub genes modulate immune cell infiltration. Although this research needs lab confirmation, we found interesting biomarkers in ESCA that may aid in diagnosis and treatment.