variant discovery

学习资料
gatk-tutorials

不同类型的基因组变异

• Homozygous(纯合) deletion
• Hemizygous(半合) deletion
• heterozygote(杂合)
• Gain(insertion) 有更多区域代表这个DNA

structural variance can be can include copy number variation. we're looking at read depth as the signal that we want to make that call. so for example in this sample this piece of the reference doesn't exist in your sample in this particular sample. and so because of that we don't see any read coverage over that region at all. and you can also have a hemizygous deletion where we're seeing half the coverage. we would expect and you can have a gain a copy number alteration

GATK Available Programs

Base Calling

Tools that process sequencing machine data, e.g. Illumina base calls, and detect sequencing level attributes, e.g. adapters

Copy Number Variant Discovery

Tools that analyze read coverage to detect copy number variants.

Coverage Analysis

Tools that count coverage, e.g. depth per allele

Diagnostics and Quality Control

Tools that collect sequencing quality related and comparative metrics

Example Tools

Example tools that show developers how to implement new tools

Flow Based Tools

Tools designed specifically to operate on flow based data

Genotyping Arrays Manipulation

Tools that manipulate data generated by Genotyping arrays

Intervals Manipulation

Tools that process genomic intervals in various formats

Metagenomics

Tools that perform metagenomic analysis, e.g. microbial community composition and pathogen detection

Methylation-Specific Tools

Tools that perform methylation calling, processing bisulfite sequenced, methylation-aware aligned BAM

Other

Miscellaneous tools, e.g. those that aid in data streaming

Read Data Manipulation

Tools that manipulate read data in SAM, BAM or CRAM format

Reference

Tools that analyze and manipulate FASTA format references

Short Variant Discovery

Tools that perform variant calling and genotyping for short variants (SNPs, SNVs and Indels)

Structural Variant Discovery

Tools that detect structural variants

Variant Evaluation and Refinement

Tools that evaluate and refine variant calls, e.g. with annotations not offered by the engine

Variant Filtering

Tools that filter variants by annotating the FILTER column

Variant Manipulation

Tools that manipulate variant call format (VCF) data

germline / somatic mutation

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4502642/

we share most of our genome with other humans. The site, most of the sites that are variant in any individual sample, are common variation that are by allelic.so the key feature of these variation is that you want to be able to compare them across many different samples.

拓展

• GATK
• snakemake samtools and bcftools

Calling genomic variants

• 1000 Genomes Project

TMBleR

nextflow流程

• nf-core/sarek
• nf-core/raredisease

SNP calling与Genotype calling不同，SNP calling只是确定基因组的位点存在变异，并不涉及对应位点的基因型，Genotype calling在SNP calling的基础上进一步确定变异位点的基因型，包括是纯合还是杂合。

Human genomic variation

3 billion sites in the human genome
Humans share 99.5% DNA with any other human
We share commonly variant sites and most of these are biallelic