Multi-family analysis with Venn variant report builder¶
Sequence Miner is a research tool for integrated analysis of genotype and phenotype data on patients. Clinical and other phenotype data can be imported into Sequence Miner through the metadata query language NOR (Non-Ordered Relational). Data fields can be sorted and filtered, allowing the user to quickly classify patients into categories (e.g., affected and unaffected). The NOR-defined subsets can then be used in Sequence Miner as input list(s) for genomic analysis applications called report builders that apply the GOR (Genomically Ordered Relational) query language.
Inheritance report builders can be used to perform single or multi-family analysis. These tools allow users to identify rare disease variants that can be inherited in a Mendelian fashion. Single-family analysis with trios or quads can be performed in the Clinical Sequence Analyzer (CSA) and the Mendelian analysis report builder, while multi-family analysis can be performed by using the Multi-family Mendelian analysis, De novo/CHZ for trios, and Venn variant analysis report builders.
The CSA and Mendelian analysis report builder in Sequence Miner analyze variants in a single index case in the context of Mendelian inheritance. Results generated from CSA or the Mendelian analysis report builder can be compared using the Venn variant analysis report builder.
Venn variant analysis can compare the reports of up to five families to identify shared variants among cases or variants that are unique to a family. A Venn diagram is generated to facilitate the analysis.
The workflow for Venn variant analysis with reports generated in CSA or the Mendelian analysis report builder is shown below:
Multi-family analysis with Venn variant analysis workflow¶
Generating Mendelian analysis reports¶
Opening Sequence Miner from CSA¶
Sequence Miner can be accessed after Mendelian analysis has been performed in CSA. To review the entire workflow of Mendelian analysis in CSA, refer to the CSA startup guide.
Results from CSA can be viewed in Sequence Miner at any point of the analysis by clicking Open query in Sequence Miner.
Once Sequence Miner has been opened from CSA, the defining query is shown at the top of the window and the number of rows are listed at the bottom. Depending on the type of analysis, this number represents the number of variants, genes, or pathways generated by the analysis.
Venn variant analysis requires four columns in the input reports: CHROM, POS, Reference, and Call. Therefore, only CSA reports under Variant view can be used as an input. In addition, the CSA report must be open in the Default view perspective in order to select it as an input in the Venn variant analysis report builder.
Generating a Mendelian analysis report in Sequence Miner¶
The workflow to generate a Mendelian analysis report is described in the Mendelian Analysis User Guide.
Running the Venn variant analysis report builder¶
After generating a Mendelian analysis report, start the Venn variant analysis by opening the Venn variant analysis report builder and entering the input parameters.
In the Sequence Miner Report Builders tab, select the Venn variant analysis report builder. You can select Variants in the Category filter to filter only Variant Reports, and then click on the Venn variant analysis report builder in the menu grid.
Select as inputs the GOR reports generated from CSA or the Mendelian analysis report builder for each family of interest. Venn variant analysis can be performed with the results of up to five families. The reports must be open in the browser in order to select them as inputs.
Next, select the type of analysis to perform. Venn variant analysis can identify variants, genes, or pathways that are shared among cases or that are unique to an index case.
After defining the parameters, initiate the analysis by clicking Create Report.
Interpreting the results¶
The Venn variant analysis report includes a Venn column for each report or family. The Venn column reports results in a Boolean manner, which means that the column contains the values “1” or “0” if a given variant is present or absent in the index case respectively. Filter on the Venn column headers to identify the number variants, genes, or pathways (depending on the type of analysis) that are present or absent in an index case.
To visualize the results and facilitate the analysis, click the Show Venn filter icon in the top right-hand toolbar. This generates a Venn diagram.
The number and percentage of variants, genes, or pathways shared among cases or that are unique to a family can be easily identified in the Venn diagram. For example, to identify the number of variants shared among cases, select the intersection area and click Apply. This generates a new table that displays only the shared variants.
Drill in reports¶
Variants of interest can be further annotated with drill-in reports.
To view available drill-in report annotations, highlight the rows containing the variants of interest, and then right-click and select Drill in Reports to open a drop-down list of annotations.
Select an annotation. For example, for information about variant-associated diseases, select var Clinical disease gene annotations.
Once a drill-in report has been selected, a new window opens with the defining query at the top and the table output at the bottom. The new output includes the annotation columns at the end of the table. Filter on the column to select a specific condition of interest.
