Fig. 1: Flow diagrams of the technological components of a 13.5-hour system for automated diagnosis and virtual acute management guidance of genetic diseases by rWGS.

Innovations described herein are indicated by orange boxes. A The order and duration of laboratory steps and technologies. EHR Electronic Health Record, EDTA EthyleneDiamineTetraAcetic acid, gDNA genomic DeoxyriboNucleic Acid, PCR Polymerase Chain Reaction, QA Quality Assurance, nt Nucleotide, SNV Single Nucleotide Variant, indel insertion-deletion nucleotide variant, SV Structural Variant, CNV Copy Number Variant, GTRx Genome-to-Treatment. B Diagram of the information flow from order placement in the EHR to return of diagnostic results together with specific management guidance for that genetic disease. rWGS Portal: Custom software system for rWGS ordering, accessioning, chain-of-custody, and return of results (v.3.2). LIMS Custom laboratory information management system for rWGS, short tandem repeat profiling, confirmatory testing (Sanger sequencing and Multiplex Ligation-dependent Probe Amplification), and inventory management (L7 informatics). IR Information resource, *: HL7/FHIR or Continuity of Care Documents, †: JSON. ‡: bcl, □: vcf.