Re-analysis of genomic data: An overview of the mechanisms and complexities of clinical adoption

Abstract

Re-analyzing genomic information from a patient suspected of having an underlying genetic condition can improve the diagnostic yield of sequencing tests, potentially providing significant benefits to the patient and to the health care system. Although a significant number of studies have shown the clinical potential of re-analysis, less work has been performed to characterize the mechanisms responsible for driving the increases in diagnostic yield. Complexities surrounding re-analysis have also emerged. The terminology itself represents a challenge because "re-analysis" can refer to a range of different concepts. Other challenges include the increased workload that re-analysis demands of curators, adequate reimbursement pathways for clinical and diagnostic services, and the development of systems to handle large volumes of data. Re-analysis also raises ethical implications for patients and families, most notably when re-classification of a variant alters diagnosis, treatment, and prognosis. This review highlights the possibilities and complexities associated with the re-analysis of existing clinical genomic data. We propose a terminology that builds on the foundation presented in a recent statement from the American College of Medical Genetics and Genomics and describes each re-analysis process. We identify mechanisms for increasing diagnostic yield and provide perspectives on the range of challenges that must be addressed by health care systems and individual patients.

Keywords: Clinical genomics; Curation; Genomics; Re-analysis; Sequence analysis.