Gene.iobio: an interactive web tool for versatile, clinically-driven variant interrogation and prioritization

Abstract

With increasing utilization of comprehensive genomic data to guide clinical care, anticipated to become the standard of care in many clinical settings, the practice of diagnostic medicine is undergoing a notable shift. However, the move from single-gene or panel-based genetic testing to exome and genome sequencing has not been matched by the development of tools to enable diagnosticians to interpret increasingly complex or uncertain genomic findings. Here, we present gene.iobio, a real-time, intuitive and interactive web application for clinically-driven variant interrogation and prioritization. We show gene.iobio is a novel and effective approach that significantly improves upon and reimagines existing methods. In a radical departure from existing methods that present variants and genomic data in text and table formats, gene.iobio provides an interactive, intuitive and visually-driven analysis environment. We demonstrate that adoption of gene.iobio in clinical and research settings empowers clinical care providers to interact directly with patient genomic data both for establishing clinical diagnoses and informing patient care, using sophisticated genomic analyses that previously were only accessible via complex command line tools.

Clin.iobio: A Collaborative Diagnostic Workflow to Enable Team-Based Precision Genomics

“…This integration with variant prioritization tools is critical in order to ensure that clin.iobio supports both phenotype-and gene-based approaches, as well as variants in genes not previously associated with the patient's phenotypes. This variant review step is powered by our previously published gene.iobio [12] tool, whereby variants in all provided genes are annotated with a comprehensive set of annotations, including ClinVar [13], gnomAD [14], and REVEL [15] for missense variants. This variant prioritization step also provides OMIM-associated [16] genetic disorders and PubMed publications associated with the selected gene.…”

“…Clin.iobio utilizes and coordinates multiple components and tools within the iobio suite of visual web-based genomics tools. These include tools for reviewing data quality metrics (based on bam.iobio [22] and vcf.iobio), generating lists of genes associated with specific phenotypes and genetic disorders (based on genepanel.iobio [21]), and variant prioritization and interpretation (based on gene.iobio [12]). Combining these code bases, clin.iobio passes the outputs from individual steps to subsequent steps, resulting in a complete start-tofinish diagnostic workflow.…”

seqr : A web‐based analysis and collaboration tool for rare disease genomics

“…Several existing tools have been developed in the academic sector for reviewing variants in defined gene lists (gene.iobio) (Di Sera et al, 2021) or for broader review and prioritization of variants in genomic analysis (Exomiser, GEMINI, PhenoDB, slivar) (Buske et al, 2013; Paila et al, 2013; P. N. Robinson et al, 2014; Sobreira et al, 2015). This is also an area of development in the commercial arena, with many fee‐based platforms available, such as those listed on ClinGen's Genomic Analysis Software Platforms list (https://clinicalgenome.org/tools/genomic-analysis-software-platform-list/).…”