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Interactive Alternative Splicing Analysis of Human Stem Cells Using psichomics.

Nuno Saraiva-Agostinho1, Nuno Luís Barbosa-Morais2

  • 1Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal. nunoagostinho@medicina.ulisboa.pt.

Methods in Molecular Biology (Clifton, N.J.)
|January 22, 2020
PubMed
Summary

Alternative splicing (AS) changes are crucial for stem cell differentiation. The psichomics R package aids in analyzing these alterations and identifying regulatory factors during stem cell to fibroblast transitions.

Keywords:
Differential gene expression analysisDifferential splicing analysisIntegrative analysesRNA-seqStemnesspsichomics

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Area of Science:

  • Molecular Biology
  • Genomics
  • Bioinformatics

Background:

  • Alternative splicing (AS) generates transcript diversity, impacting cellular processes like stem cell differentiation.
  • Splicing factors linked to epithelial-to-mesenchymal transition are also associated with pluripotency.
  • Next-generation sequencing (RNA-seq) has enabled genome-wide AS studies using transcriptomic data.

Purpose of the Study:

  • To introduce the psichomics R package for AS quantification and integrative analysis of transcriptomic data.
  • To investigate AS changes during human stem cell differentiation into fibroblasts.
  • To identify RNA-binding protein regulators associated with observed AS alterations.

Main Methods:

  • Utilized the psichomics R package for AS quantification and differential analysis.
  • Applied dimensionality reduction, median- and variance-based analyses for AS and gene expression.
  • Performed correlation analyses on large human tissue transcriptomic cohorts to identify regulatory proteins.

Main Results:

  • Identified significant AS alterations between human stem cells and fibroblasts.
  • Detected changes in the expression of candidate RNA-binding protein regulators.
  • Confirmed both novel and previously reported AS events linked to stem cell differentiation.

Conclusions:

  • The psichomics R package facilitates efficient AS analysis in large datasets.
  • Specific AS alterations and regulatory factor changes are associated with stem cell differentiation into fibroblasts.
  • This study provides insights into the molecular mechanisms governing stem cell fate decisions.