The AnnotSV webserver in 2023: updated visualization and ranking

Abstract

Much of the human genetics variant repertoire is composed of single nucleotide variants (SNV) and small insertion/deletions (indel) but structural variants (SV) remain a major part of our modified DNA. SV detection has often been a complex question to answer either because of the necessity to use different technologies (array CGH, SNP array, Karyotype, Optical Genome Mapping…) to detect each category of SV or to get an appropriate resolution (Whole Genome Sequencing). Thanks to the deluge of pangenomic analysis, Human geneticists are accumulating SV and their interpretation remains time consuming and challenging. The AnnotSV webserver (https://www.lbgi.fr/AnnotSV/) aims at being an efficient tool to (i) annotate and interpret SV potential pathogenicity in the context of human diseases, (ii) recognize potential false positive variants from all the SV identified and (iii) visualize the patient variants repertoire. The most recent developments in the AnnotSV webserver are: (i) updated annotations sources and ranking, (ii) three novel output formats to allow diverse utilization (analysis, pipelines), as well as (iii) two novel user interfaces including an interactive circos view.

Graphical Abstract

Figure 1.

Schematic overview of the AnnotSV webserver workflow. The webserver architecture comprises a two-tiered framework: first an annotation engine with AnnotSV (submitting a query, processing the annotations) and second a visualization and filtering interface with knotAnnotSV and vcf2circos (showing results, generating the visualization and filtering system). The variantconvert module is used for VCF conversion. Part of the workflow with an update compared to the previous version is highlighted using a black dotted rectangle.

Figure 2.

vcf2circos interface overview. The circos represents the chromosome in a circular view allowing a quick overview along the whole genome or selected chromosomes. The interface includes multiple annotations tracks: chromosomes, cytobands, genes and morbid OMIM genes (red), GC content, CNV dedicated regions (from 0 to 5 and more copies) including inversions. The different SV are represented using the following scheme (gnomAD inspired (42)): deletion (DEL in dark red), duplication (DUP in blue), insertion (INS in purple), inversion (INV in orange) and CNV with no specific type (CNV in green). The popup includes various information such as the SV coordinates and length, overlapping transcripts and genes, haploinsufficiency cytoband…