Computational methods to study human transcript variants in covid-19 infected lung cancer cells

Jiao Sun, Naima Ahmed Fahmi, Heba Nassereddeen, Sze Cheng, Irene Martinez, Deliang Fan, Jeongsik Yong, Wei Zhang

Research output: Contribution to journalArticlepeer-review

Abstract

Microbes and viruses are known to alter host transcriptomes by means of infection. In light of recent challenges posed by the COVID-19 pandemic, a deeper understanding of the disease at the transcriptome level is needed. However, research about transcriptome reprogramming by post-transcriptional regulation is very limited. In this study, computational methods developed by our lab were applied to RNA-seq data to detect transcript variants (i.e., alternative splicing (AS) and alternative polyadenylation (APA) events). The RNA-seq data were obtained from a publicly available source, and they consist of mock-treated and SARS-CoV-2 infected (COVID-19) lung alveolar (A549) cells. Data analysis results show that more AS events are found in SARS-CoV-2 infected cells than in mock-treated cells, whereas fewer APA events are detected in SARS-CoV-2 infected cells. A combination of conventional differential gene expression analysis and transcript variants analysis revealed that most of the genes with transcript variants are not differentially expressed. This indicates that no strong correlation exists between differential gene expression and the AS/APA events in the mock-treated or SARS-CoV-2 infected samples. These genes with transcript variants can be applied as another layer of molecular signatures for COVID-19 studies. In addition, the transcript variants are enriched in important biological pathways that were not detected in the studies that only focused on differential gene expression analysis. Therefore, the pathways may lead to new molecular mechanisms of SARS-CoV-2 pathogenesis.

Original languageEnglish (US)
Article number9684
JournalInternational journal of molecular sciences
Volume22
Issue number18
DOIs
StatePublished - Sep 2021

Bibliographical note

Funding Information:
Funding: The study was supported by the National Science Foundation grant IIS1755761 and FET2003749 and National Institutes of Health 2R01GM113952. Publication costs are funded by the National Science Foundation grant FET2003749.

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • 3-UTR
  • Alternative polyadenylation
  • Alternative splicing
  • COVID-19
  • RNA-seq
  • Transcript variants
  • A549 Cells
  • SARS-CoV-2/genetics
  • Humans
  • Transcriptome/genetics
  • COVID-19/virology
  • Gene Expression Regulation, Viral
  • Genes, Viral

PubMed: MeSH publication types

  • Journal Article

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