RNA-Seq Pipeline Overview
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About This MicroSim
This MicroSim walks through the RNA-seq pipeline as an animated flowchart, from biological sample preparation through computational analysis.
Pipeline Stages
- RNA Extraction — Isolate total RNA from biological samples (cells, tissues)
- Library Preparation — Convert RNA to cDNA, fragment, add adapters for sequencing
- Sequencing — Generate millions of short reads on an Illumina platform
- QC / Trimming — Assess read quality (FastQC), remove adapters and low-quality bases (Trimmomatic)
- Alignment — Map reads to a reference genome or transcriptome (STAR, HISAT2)
- Quantification — Count reads per gene to measure expression levels (featureCounts, Salmon)
- Differential Expression Analysis — Identify genes with significant expression changes between conditions (DESeq2, edgeR)
How to Use
- Step through — Advance through each stage to see what processing occurs
- Read descriptions — Each stage explains the biological purpose, computational tools, and output format
- Follow the data transformation — Watch how RNA molecules become a table of differentially expressed genes
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Lesson Plan
Grade Level
College introductory bioinformatics
Duration
15-20 minutes
Prerequisites
- Understanding of gene expression (mRNA as a measure of gene activity)
- Basic concept of DNA sequencing
- Awareness of experimental design (conditions, replicates)
Activities
- Exploration (5 min): Step through all stages. At each, note the key tool and the output format.
- Wet Lab vs. Dry Lab (5 min): Identify which stages are wet lab (bench work) and which are dry lab (computational). Where is the transition?
- Discussion (5 min): Why do we need biological replicates for differential expression analysis? What happens to statistical power with only one replicate per condition?
- Assessment (5 min): Answer the reflection questions below.
Assessment
- Why is library preparation necessary before sequencing RNA?
- What is the difference between alignment-based quantification (STAR + featureCounts) and pseudo-alignment (Salmon)?
- Why does differential expression analysis require statistical testing rather than simply comparing raw read counts?
- Name two common tools for differential expression analysis and describe what statistical model they use.