Practical Somatic Variant Analysis in Cancer Genomics

A 3-day hands-on online workshop covering the complete somatic variant analysis workflow: from sequencing data quality control to variant annotation and interpretation.

Dates: 27-29 April 2026, 2:00-5:00 PM CEST (Berlin time)

Instructor: Dr. Flavio Lombardo — University Hospital Basel / University of Basel

Course overview

This workshop provides participants with practical skills in cancer genomics analysis, focusing on somatic variant detection and annotation. The course covers the complete workflow from raw sequencing data to the identification of potentially pathogenic mutations in cancer genomes.

Day 1 — Foundations & Data Preparation

• Cancer genomics fundamentals: somatic vs. germline mutations
• Sequencing data quality control and preprocessing
• Read alignment and BAM file analysis
• Introduction to data formats (FASTQ, BAM, VCF)

Day 2 — Somatic Variant Calling with GATK4

• Principles of somatic variant detection
• GATK4 Mutect2 pipeline with matched tumor-normal samples
• Variant filtering strategies
• Copy number variation calling with CNVkit

Day 3 — Variant Annotation & Interpretation

• Functional annotation with Ensembl VEP
• Integration with cancer-relevant databases (ClinVar, REVEL, AlphaMissense)
• Variant Allele Frequency (VAF) analysis
• Variant prioritization and visualization in R

Course data

Exercises use whole-exome sequencing (WES) data from matched tumor-normal cancer cell lines (HCC1395/HCC1395BL) with all reference files pre-staged:

• GRCh38 reference genome (chr6 + chr17)
• Panel of Normals (1000 Genomes)
• gnomAD population frequencies
• ClinVar, REVEL, and AlphaMissense annotation databases

Prerequisites

• Basic familiarity with the command line
• Some programming experience (preferably R)
• A computer with a web browser (the course environment is fully cloud-based)

Running the course website locally

This website is built with Quarto. To render it locally:

1. Install Quarto

Download and install from quarto.org/docs/get-started.

2. Install R dependencies

The Day 3 R analysis pages require:

install.packages(c("readr", "ggplot2", "dplyr", "tidyr", "stringr"))

3. Clone and render

git clone git@github.com:flalom/practical-somatic-variant-analysis.git
cd practical-somatic-variant-analysis
quarto preview

This starts a local preview server at http://localhost:4848/.

Repository structure

├── index.qmd                    # Home page
├── precourse_preparations.qmd   # Prerequisites and setup info
├── course_schedule.qmd          # 3-day schedule
├── first_login.qmd              # Partecipant setup on Day 1
├── day1_foundations.qmd         # Day 1 QC & exercises
├── day2_variant_calling.qmd     # Day 2 Mutect2 & exercises
├── day3_annotation.qmd          # Day 3 VEP annotation exercises
├── day3_R_analysis.qmd          # Day 3 R visualization exercises
├── day3_vaf_analysis.qmd        # Day 3 VAF analysis exercises
├── cnv_example_using_vep.qmd    # Bonus: CNV annotation with VEP
├── slides/                      # Lecture slide decks (Revealjs)
│   ├── 01_course_intro.qmd
│   ├── 02_introduction_cancer_variants.qmd
│   ├── 03_somatic_variant_calling.qmd
│   └── 04_variant_annotation.qmd
├── scripts/                     # Exercise scripts (bash)
├── Docker/                      # Dockerfiles for course environments
│   ├── vscode/                  # VSCode code-server (main environment)
│   └── rstudio/                 # RStudio server (Day 3 R analysis)
├── _quarto.yml                  # Quarto site configuration
└── assets/                      # Images and static files

Attribution

This course builds upon materials originally developed for SIB Swiss Institute of Bioinformatics by Flavio Lombardo and Geert van Geest, with additional inspiration from the Precision Medicine Bioinformatics course by the Griffith Lab.

License

CC BY 4.0 — Flavio Lombardo. Originally developed for SIB Swiss Institute of Bioinformatics.