Workflow for the Implementation of Precision Genomics in Healthcare

Abstract

To enable the implementation of precise genomics in a local healthcare system, we devised a pipeline for filtering and reporting of relevant genetic information to healthy individuals based on exome or genome data. In our analytical pipeline, the first tier of filtering is variant-centric, and it is based on the selection of annotated pathogenic, protective, risk factor, and drug response variants, and their one-by-one detailed evaluation. This is followed by a second-tier gene-centric deconstruction and filtering of virtual gene lists associated with diseases, and VUS-centric filtering according to ACMG pathogenicity criteria and pre-defined deleteriousness criteria. By applying this filtering protocol, we were able to provide valuable insights regarding the carrier status, pharmacogenetic profile, actionable cardiovascular and cancer predispositions, and potentially pathogenic variants of unknown significance to our patients. Our experience demonstrates that genomic profiling can be implemented into routine healthcare and provide information of medical significance.

Keywords: clinical practice; exome; genome; implementation; personalized medicine; precision genomics.

FIGURE 1

Operational and analytical workflows applied in this study. (A) Operational workflow starting with patient recruitment, pre-test genetic counseling, genome, or exome sequencing and bioinformatic analyses, representative sample of reports, and post-test genetic counseling. All adapted images used in this figure have a CC license. (B) Description of the analytical workflow for variant filtration.