Banca de DEFESA: THAIS TEIXEIRA OLIVEIRA
Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.STUDENT : THAIS TEIXEIRA OLIVEIRA
DATE: 30/09/2024
TIME: 14:00
LOCAL: Google Meet (link: https://meet.google.com/qed-sbdc-boh)
TITLE:
COVID-19 Transcriptomics: Identification of Potential Biomarkers and Molecular Mechanisms of Disease Severity.
KEY WORDS:
SARS-CoV-2, RNA-seq, Immune response, Biomarkers, Transcription factors.
PAGES: 135
BIG AREA: Ciências Biológicas
AREA: Genética
SUMMARY:
Transcriptome studies were conducted during the COVID-19 pandemic to investigate possible immune responses to SARS-CoV-2, identify potential treatment targets, and identify disease biomarkers. It is, however, important to note that many of these datasets remain underutilized; some may only contain a few patients. Larger, more comprehensive studies are crucial for drawing more reliable and generalizable conclusions. They can help identify consistent patterns and biomarkers across diverse populations, leading to more effective treatment strategies. Additionally, such studies enhance the statistical power needed to validate findings and ensure their applicability in real-world scenarios. To improve the search for molecular targets and biomarkers, this work evaluated the literature generated during the pandemic around transcriptomics and its main results. The review systematically analyzed 203 published articles that performed transcriptomic experiments in patients infected with SARS-CoV-2 and uninfected controls. These studies highlighted the dysregulation of interferon-stimulated genes (ISGs), cytokines and chemokines, and genes related to neutrophil activation. We also performed an integrated reanalysis of six RNA-seq datasets from public databases. This analysis allowed an increase in the number of patients evaluated, increasing data reliability and genetic variability, including patients from different countries. We analyze datasets from COVID-19 patients to identify potential targets and pathways associated with disease progression and discover biomarkers associated with severity. Three whole blood datasets and one leukocyte dataset from intensive care unit (ICU) patients were analyzed and compared with ICU patients who were negative for COVID-19. In addition, nasal swabs and PBMC data were also analyzed. As a result, it was observed that severe COVID-19 patients exhibited overexpression of genes encoding extracellular exosome proteins, endomembrane system proteins, and neutrophil granules. Furthermore, key targets such as S100A9, LY96, GAPDH, RAB1B, NFKBIA, and CD63 were highlighted, which may play an important role in the cellular response to infection. On the other hand, patients with severe COVID-19 exhibited downregulation of genes encoding components of the T-cell receptor complex and nucleolus proteins, including TP53, IL2RB, and NCL. Finally, master regulator prediction analysis considering the set of up- and downregulated genes showed that SPI1 is a transcription factor associated with upregulated genes and TP53, MYC, and MAX have an essential role in regulating the expression of downregulated genes during COVID-19. To validate testable biomarkers in serum, the highlighted genes were tested in serum from mild and severe COVID-19 patients. Several of these genes were not cited in previous studies, indicating that this study identified important targets that may provide insights into the molecular pathophysiology of SARS- CoV-2 infection. Furthermore, the identification of transcriptional factors that regulate the expression of genes involved in infection and the inflammatory response may be essential for advancing our understanding of the disease and for the search for new therapeutic targets.
COMMITTEE MEMBERS:
Presidente - 1149647 - LUCYMARA FASSARELLA AGNEZ LIMA
Interna - 1199127 - SILVIA REGINA BATISTUZZO DE MEDEIROS
Externo ao Programa - 1715230 - JOSELIO MARIA GALVAO DE ARAUJO - UFRNExterno à Instituição - GLORIA REGINA FRANCO - UFMG
Externo à Instituição - ÂNDREA KELY CAMPOS RIBEIRO DOS SANTOS - UFPA