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Welcome!

This lesson will introduce you to the basics of gene expression analysis using RNA-Seq (short for RNA sequencing). Due to the considerable progress and constant decreasing costs of RNA-Seq, this technique has became a standard technique in biology.

It is going to be fun and empowering! We will use the shell (covered on the first day of this submodule) and R (covered on the second day of the submodule) to perform our RNA-Seq analyses and visualisations. Before you begin, be sure you are all set up for the lesson. See and complete the [Setup]({{ site.baseurl }}{% link setup.md %}) section.

Main learning objectives

After completing this lesson, you should be able to:

  • Assess the quality of RNA-seq sequencing data (“reads”) using the command-line instructions.
  • Align RNA-seq reads to a reference genome using a splice-aware aligner (e.g. STAR).
  • Generate a count matrix from the RNA-seq data alignment.
  • Perform a QC of your experiment through Principal Component Analysis (PCA) and sample clustering.
  • Execute a differential gene expression analysis using R and the DESeq2 package.
  • Be able to create key plots: volcano plot, heatmap and clustering of differentially expressed genes.
  • Provide a biological interpretation to differentially expressed genes through ORA/GSEA analyses and data integration.

Schedule

Setup
09:00 - 10:00 [Introduction & QC]({{ site.baseurl }}{% link introduction.md %}) What can I learn by doing this RNA-Seq lesson?
What are the tools that I will be using?
How do I perform a quality check of my RNA-seq fastq files with FastQC?
How can I remove RNA-seq reads of low quality?
10:00 - 11:00 [Aligning]({{ site.baseurl }}{% link aligning.md %}) How do I align my reads to a reference genome using STAR and hisat2?
11:00 - 11:45 [Counting]({{ site.baseurl }}{% link counting.md %}) What is a BAM file?
How do I determine the number of reads that map within genes?
1:00 - 2:00 [Differential expression]({{ site.baseurl }}{% link diffexp.md %}) How do I know that my RNA-seq experiment has worked according to my experimental design?
What is a Principal Component Analysis (PCA) and how can I use it?
What are factor levels and why is it important for different expression analysis?
How can I call the genes differentially regulated in response to my experimental design?
What is a volcano plot and how can I create one?
What is a heatmap and how can it be informative for my comparison of interest?
2:00 - 3:00 [Over-representation analysis]({{ site.baseurl }}{% link ora.md %}) Given a list of differentially expressed genes, how do I search for enriched functions?
3:00 - 3:45 [Gene set enrichment]({{ site.baseurl }}{% link gsea.md %}) What is the difference between an over-representation analysis (ORA) and a gene set enrichment analysis (GSEA)?

Credits

This lesson is heavily based on teaching materials from the Harvard Chan Bioinformatics Core (HBC) in-depth NGS data analysis course and RNA-seq lesson from the ScienceParkStudyGroup.