Using this software0. For impatient users
1. Data inputs
2. Create a project
3. Annotate a project
Using user annotation track
4. Filter for quality scores
5. Main user interface
6. SVA genome browser
7. SVA tables
8. Selecting genes or regions
Bio-pathway or GO
Fisher's exact test
10. Exome or targeted capture sequencing
Using SVA Analysis functions - Gene Prioritization
The 'Gene Prioritization' function produces a list of protein coding genes that are 'knocked out' by homozygous variants in case genomes. This analysis prioritizes genes by the number of cases containing homozygous protein truncating or non-synonymous genetic variants, absent in control genomes. By this definition, different variants in the same gene are allowed and contribute equally to the ranking of this gene. In other words, this analysis tries to answer this simple question: do you see enrichment of protein-truncating (optionally, or non-synonymous) variants in any gene in the cases, when compared to control genomes?
Your SVA project must contain at least one case and one control for this function to work. Your SVA project must contain at least two cases for this function to reliably prioritize knocked out genes (with only one case, all homozygous knock out variants are listed but they all have the same liklihood of impacting case phenotype).
To access the gene prioritization function, go to the menu 'Analysis -> Gene prioritization'. The Genome Browser must be initilized to run this function.
This will open a 'Prioritization analysis' window. This window will allow you to customize this function in four different ways, explained below. The 'Prioritization analysis' window looks like this:
Function of genetic variantThis section allows you to select the types of 'knock out' variants you wish to include. The three options are:
Criteria for homozygous variants
This section allows you to adjust the coverage you want to require for a homozygous variant. This will impact the number of variants that show up on your gene prioritization output. If you do not care about coverage (i.e. confidence) of the homozygous variants, you can uncheck 'Minimum coverage for a homozygous variant'. Otherwise the default parameters are set as follows:
A brief explanation of default parameters for homozygous variants:
Genetic modelThis section allows you to select the genotype of the variant (heterozygous or homozygous) that you will allow to be present in your control genomes. The target variations in your cases are unaffected by this setting (still homozygous knock out variants).
After selecting your desired settings in the 'Prioritization analysis' window, click 'Output to. . . ' select the file you wish to save your file to, name your file by entering a name into the 'File Name' field and select 'Save'.
After clicking 'Save', the path to this file will be displayed in the 'Prioritization analysis' window, then select 'Analyze'.
Sample output (.txt file):
© 2011 Dongliang Ge, PhD.