Teaching material for the course HP-F9 "Bioinformatical Analysis of Large-scale Data in Modern Genomics" (13 April - 22 May 2026)
This repository contains slide decks developed as practical course material for second semester Master's students enrolled in the Major Cancer Biology program at the German Cancer Research Center (DKFZ), Heidelberg. The course is a one-week practical introduction to genomics, covering bioinformatic analysis of large-scale data in the context of modern genomics research.
| # | Slide Deck |
|---|---|
| 1 | Overview |
| 2 | Bioinformatics History |
| 3 | Sequencing Technologies |
| 4 | Unix Fundamentals |
| 5 | Introduction to FASTA & FASTQ |
| 6 | Unix Utilities |
| # | Slide Deck |
|---|---|
| 7 | Reference Genome |
| 8 | Quality Control: FastQC & fastp |
| 9 | Sequence Alignment |
| 10 | SAM Format & samtools |
| # | Slide Deck |
|---|---|
| 11 | Genetic Variation, History & Heredity |
| 12 | Variant Calling |
| 13 | bcftools |
| 14 | Variant Annotation |
| # | Slide Deck |
|---|---|
| 16 | Cancer Genomics Basics |
| File | Description |
|---|---|
| 01-R_exercises.Rmd | Introductory R exercises |
| 02-day5_variant_analysis.Rmd | End-to-end variant analysis in R |
02-day5_variant_analysis.Rmd brings together the outputs from Day 3 and Day 4 for a comparative analysis entirely in R (no new command-line tools). It covers:
Part 1 — Germline variant analysis (Day 3 output: variants.tsv)
- Loading and exploring ~88,000 raw germline variant calls on chr22 (HG003 healthy individual)
- Computing Variant Allele Frequency (VAF) from DP4 read counts
- Step-by-step filtering funnel: quality → protein-coding → exonic → rare (gnomAD AF < 1%)
- Consequence type distribution (missense, loss-of-function, intronic, etc.)
- Ti/Tv ratio calculation and substitution spectrum (C→T deamination signature)
- Top genes by germline variant burden
Part 2 — Somatic variant analysis (Day 4 output: somatic.filtered.annotated.tsv)
- Loading Mutect2 tumour-normal paired calls with FILTER labels
- Filtering to PASS + rare variants
- Somatic consequence distribution and Ti/Tv ratio (C→A oxidative damage signature)
- Normal AF vs Tumour AF scatter plot to distinguish true somatic from germline leakage
- Tumour VAF by consequence — clonal vs subclonal mutations
- Top mutated genes in the tumour
Part 3 — Germline vs Somatic VAF comparison
- Stacked histogram and density overlay of VAF distributions from both datasets
- Key concept: germline shows a bimodal peak (het ≈ 0.5, hom ≈ 1.0); somatic shows a broad low distribution reflecting tumour heterogeneity and clonal evolution
This teaching material is licensed under Creative Commons Attribution 4.0 International (CC BY 4.0).
You are free to share and adapt the material for any purpose, provided appropriate credit is given to the original author(s).