Figure 2.

The human pipeline of clinical exome and genome sequencing. The term pipeline is applied by bioinformaticians for a set of defined steps that lead from raw next-generation sequencing reads to variant call files (.vcf ± subsequent interpretation) as a central component of next-generation sequencing–based diagnostic tests (blue frame). To implement clinical exome and genome sequencing, we provide the current state of our pipeline from request to report and clinical management. The principle pathway is indicated by the following numbers in orange circles: (1) institutional review, (2) cost estimation, (3) preauthorization, (4) accessioning, (5) billing, (6) clinical exome and genome sequencing, (7) report and report consultation, and (8) patient financial counseling. Given that the personnel, their interactions, and professional qualifications play a central role in the clinical environment, we applied the term human pipeline and provide professional degrees and years of experience after training of the least experienced team member serving in each role. Detailed workflow diagrams can be found in Supplemental Figures S3–S8. AD, administrative personnel with various degrees; BS, Bachelor of Science; CPT, Current Procedural Terminology; DCC logo, deductible, copay, co-insurance; EBM, evidence-based medicine; GC, genetic counselor with board certification; HD, high-school diploma with on-the-job training; HIS, hospital information system; IT, information technology; LIS, laboratory information system; LMN, Letter of Medical Necessity; MD, medical school degree plus board examination; MS, Master of Science; PBE, practice-based evidence; PhD, doctor of philosophy in bioinformatics; Umbrella (logo), insurance covered part of the payment.