Configuration

Variant Explorer is fully configurable editing the 2 configuration files present in the app folder.

1. App_configuration.json: configure app options for plotting and some expected columns
2. Filters_settings.json: configure filters and presets

However, some columns are always expected in the input data:

• rec_id: unique ID of the specific line
• var_id: unique ID of the variant
• consequence: consequence of the variant
• var_type: variant type (like SNV, INDEL, etc)
• chrom,pos,ref,alt: genomic coordinates, ref and alt alleles
• gene: affected gene
• GT_sampleID: genotype for each sample
• GQ_sampleID: GQ for each sample

App_configuration

The app configuration is a standard json file organized as follows

{
"var_groups": {
    "consequence_groups": {
    "group1": ["consequence1","consequence2", "..."]
    },
    "var_type_groups": {
    "group1": ["var_type1","var_type2", "..."]
    }
},
"segregation_cols": {
    "het_affected": "het_aff",
    "het_unaffected": "het_unaff",
    "hom_affected": "hom_aff",
    "hom_unaffected": "hom_unaff",
    "comphet_affected": "comphet_aff",
    "dnm_affected": "sup_dnm"
},
"plot_axes": {
    "genes_axes_options": {
    "label1": "col_name1",
    "label2": "col_name2"
    },
    "variants_axes_options": {
    "label1": "col_name1",
    "label2": "col_name2"
    },
    "variants_bar_options": {
    "label1": "col_name1",
    "label2": "col_name2"
    }
},
"fill_na": {
    "fill_na_vars" : {
    "col_name1": "replace value1",
    "col_name2": "replace value2"
    },
    "fill_na_genes" : {
    "col_name1": "replace value1",
    "col_name2": "replace value2"
    }
}
}

Configuration sections:

“var_groups”:

“consequence_groups”:

a series of lists defining variants groups based on variant consequence "lof_vars": ["frameshift", "exonic_sv","stop lost","stop gain","start loss","splice_acceptor_variant","splice_donor_variant"]

“var_type_groups”:

a series of lists defining variants groups based on variant type "sv_vars": ["DEL","DUP","INV","DEL:ME"]

“segregation_cols”:

definition of the columns containing counts of affected/unaffected carriers for each genotype

{
"het_affected": "het_aff",
"het_unaffected": "het_unaff",
"hom_affected": "hom_aff",
"hom_unaffected": "hom_unaff",
"comphet_affected": "comphet_aff",
"dnm_affected": "sup_dnm"
}

“plot_axes”:

This section define the columns used to generate overview and filters plots for genes and variants

“genes_axes_options”:

Columns used in the genes filters scatter-plots, in the formate label: column_name. The labels are shown in a drop-down box to configure the corresponding plot Example:

{
"GADO Zscore": "gado_zscore",
"Exomiser Pheno score": "exomiser_gene_pheno_score",
"gnomAD pLI": "pLI_gnomad",
"GDI phred": "GDI_phred",
"RVIS intolerance": "RVIS",
"EDS reg space score": "EDS"
}

“variants_axes_options”:

Columns used in the variants filters scatter-plots, in the formate label: column_name. The labels are shown in a drop-down box to configure the corresponding plot Example:

{
"Maximum population AF": "max_pop_af",
"CADD phred": "CADD_PhredScore",
"DANN score": "DANN_score",
"ReMM score": "ReMM_score",
"SpliceAI score": "SpliceAI_SNP_SpliceAI_max",
"REVEL score": "REVEL_score",
"MCAP score": "MCAP_score",
"LinSight score": "LinSight"
}

“variants_bar_options”:

Columns used in the variants filters bar plots, in the formate label: column_name. The labels are shown in a drop-down box to configure the corresponding plot Example:

{
"Region type": "reg_type",
"Variant consequence": "consequence",
"Variant type": "var_type",
"PanelApp": "PanelApp",
"Chromosome": "chr"
}

“fill_na”:

This section define how to fill NA values for gene and variants scores. For each column it is possible to assign a specific value to replace NAs

“fill_na_vars”:

NA replacement values for variants table, in the format col_name: replace_value Example

{
"max_pop_af": 0,
"cohort_af": 0,
"DANN_score": 99,
"CADD_PhredScore": 99,
"PhyloP100": -99
}

“fill_na_genes”:

NA replacement values for genes table, in the format col_name: replace_value Example

{
"GDI_phred": -99,
"RVIS": -99,
"pLI_gnomad": 99,
"EDS": 99
}

Filters configuration

The app configuration is a standard json file organized as follows

"GENES": {
    "DEFINITIONS": {
        "numeric_fields": {
            "col_name1": ["label1", ">=", "default_value"],
            "col_name2": ["label2", "<", "default_value"]
        }
    },
    "GROUPS": {
        "global": {
            "associated_values": ["col_name1", "col_name2"]
        }
    },
    "PRESETS": {
        "global": {
            "default": "preset1",
            "configuration": {
                "preset1": {
                    "logic": "OR",
                    "values" : {
                        "column1": value1,
                        "column2": value1
                    }
                },
                "preset2": {
                    "logic": "OR",
                    "values" : {
                        "column1": value2,
                        "column2": value2
                    }
                }
            }
        }
    }
},
"VARIANTS": {
    "DEFINITIONS": {
        "numeric_fields": {
            "col_name1": ["label1", ">=", "default_value"],
            "col_name2": ["label2", "<", "default_value"]
        },
        "factors_fields": {
            "col_name1": ["label1", "%in%", "default_value"],
            "col_name2": ["label2", "grep", "default_value"]
        },
        "binary_fields": {
            "col_name1": ["label1", "include", "default_true/false"],
            "col_name2": ["label2", "exclude", "default_true/false"]
        }
    },
    "FACTORSMAP": {
        "col_name1": {
            "label1": "factor1",
            "label2": "factor2",
        },
        "reg_type": {
            "Closest gene":  "closest_gene",
            "From database": "reg_db"
        }
    },
    "GROUPS": {
        "global": {
            "associated_values": ["col_name1","col_name2"]
        },
        "group1": {
            "definition": ["consequence", ["value1","value2"]],
            "associated_values": ["col_name1","col_name2"]
        }
    },
    "PRESETS": {
    "global": {
        "default": "strict",
        "configuration": {
            "strict": {
                "logic": "AND",
                "values": {
                    "column1": value1,
                    "column2": value1
                }
            },
            "balanced": {
                "logic": "AND",
                "values": {
                    "column1": value2,
                    "column2": value2
                }
            }
        }
    },
    "group1": {
        "default": "balanced",
        "configuration": {
            "strict": {
                "logic": "AND",
                "values": {
                    "column1": value1,
                    "column2": value1
                }
            },
            "balanced": {
                "logic": "AND",
                "values": {
                    "column1": value2,
                    "column2": value2
                }
            }
        }
    }
},
"TOOLTIPS": {
    "col_name1": "tooltip_text_1",
    "col_name2": "tooltip_text_2"
}