Clinical Genomics Uppsala inheritance disease pipeline for WGS made as a snakemake workflow.
The pipeline will be build one step at a time with step 1 and 2 being the most crucial. Where possible, hydra-genetics modules (https://github.com/hydra-genetics) will be used. Part of pipeline will not be in hydra-genetics from the beginning but will be changed into modules when there is time.
Steg 1: SNV and indel analysis
- GATK best practices to get analysis ready bam
- deepVariant (+ GLNexus?) for calling
- kinship and sex-check with peddy (maybe have an easy this many reads tells this story too, can find XXY and homozygote females)
- coverage for gene panels
Steg 2: CNV, and other SV: inversions, deletion and duplications for Moon
- manta
- CNVnator
- When these work and other parts of the pipeline it is possible to continue buildning this part. What is good right now? (Tiddit, CNVkit, delly, others?)
- Combine the results from different callers: SVdb to one vcf-file
- SVdb will help remove false positives?
- Region Of Homozygosity and UniParental Disomy
Steg 3: SMA
- SMNCopyNumberCaller (https://github.com/Illumina/SMNCopyNumberCaller, https://www.nature.com/articles/s41436-020-0754-0?proof=t)
- SMNca (https://onlinelibrary.wiley.com/doi/full/10.1002/humu.24120)
- other ways to handle SMN1 och SMN2?
Steg 4: Repeat expansions
- ExpansionHunter
- if annotation is needed: STRanger
- histogram with size distribution per sample
- REViewer? Illumina
- Fragile X
Steg 5: Mitochondria
- heteroplasmy (sensitivity)
Steg 6: RNA
#Software or thoughts for future
- Telomerecat is a tool for estimating the average telomere length (TL) for a paired end, whole genome sequencing (WGS) sample (Panos kanske är intresserad av svaret)
- Cyrius for good call of CYP2D6
- What data is needed more than vcf? QC and figures.