This course will introduce biologists and bioinformaticians into the field of Structural Variant (SV) detection and comparison.  Structural Variants are 50bp or larger genomic alterations that impact multiple diseases and phenotypes. We will cover a broad range of software and analysis workflows that extend over the spectrum from short to long read approaches using assembly or mapping based methods to identify these types of variants.  We will further provide insights on how to filter and assess these SV and obtain a trio/population level VCF file by comparing SV.  Lastly we will provide suggestions to assess their functional impact and how to prioritize / rank and QC  these variants further.

The course is structured in modules over three days. Each day will include an introductory lecture with class discussion of key concepts. The remainder of each day will consist of practical hands-on sessions. These sessions will involve a combination of both mirroring exercises with the instructor to demonstrate a skill as well as applying these skills on your own to complete individual exercises. After and during each exercise, interpretation of results will be discussed as a group.

The course is aimed at researchers interested in learning how to compare genomes and what can be learned from genomic similarities as well as variations. It will include information useful for both beginners and more advanced users. We will start by introducing general concepts of comparative genomics. On this basis, we will then continue to describe all major analysis steps from the raw sequencing data via the identification of variations to an assessment of their impact on the phenotype.
 
Attendees should have a background in biology. There will be a mix of lectures and hands-on practical exercises using command line Linux. We will therefore dedicate one session to introduce basic and advanced Linux concepts for processing data on Amazon cloud (AWS). Attendees should also have some familiarity with genomic data and formats such as that arising from NGS sequencing experiments.

By the end of the course, participants will be able to:

 - Identify Structural Variants using mapping or assembly approach
 - Identify Structural Variants from long and short read data.
 - Compare and filtering Structural Variants.
 - Annotate of Structural Variants (gene overlap, Population frequency)
 - Generate a trio / population VCF file for Structural Variants
 - Identify mosaic / somatic Structural Variants

We will use data from a human genome sequences project for the example analyses
We encourage the participants to bring, analyze (if possible) and discuss their own data

Monday: 2-8 pm Berlin time.

Lecture 1
 General introduction
 File formats: FastQ, SAM, BAM, VCF
 Introduction in de novo assembly strategies, best practices and quality control
 Introduction in reference mapping, best practices and quality control
      -Short reads
      -Long reads

Lab 1
 Setting up the computers/AWS instances
 Differences between short and long reads
 First steps in genome assembly
     -Short and long reads
 First steps in genome mapping
     -Short and long reads

Tuesday: 2-8 pm Berlin time.

Lecture 2
 Variant calling
     - Short reads and pitfalls
     - Long reads

Lab 2
 First steps in variant calling on genome assemblies
     - Short reads
     - Long reads
 First steps in variant calling on reference genome mapping
        -Short reads
        -Long reads

Wednesday: 2-8 pm Berlin time.

Lecture 3
In-depth variant calling for long reads
Variant calling annotation

Lab 3
In-depth long read variant calling for long reads
   -Population/trios
   -Low-frequency / mosaic Variant calling
   -Somatic variant calling
Summary

Should you have any further questions, please send an email to info@physalia-courses.org