Genome sequencing in the clinic: the past, present, and future of genomic medicine

Abstract

Genomic sequencing has undergone massive expansion in the past 10 yr, from a rarely used research tool into an approach that has broad applications in a clinical setting. From rare disease to cancer, genomics is transforming our knowledge of biology. The transition from targeted gene sequencing, to whole exome sequencing, to whole genome sequencing has only been made possible due to rapid advancements in technologies and informatics that have plummeted the cost per base of DNA sequencing and analysis. The tools of genomics have resolved the etiology of disease for previously undiagnosable conditions, identified cancer driver gene variants, and have impacted the understanding of pathophysiology for many diseases. However, this expansion of use has also highlighted research's current voids in knowledge. The lack of precise animal models for gene-to-function association, lack of tools for analysis of genomic structural changes, skew in populations used for genetic studies, publication biases, and the "Unknown Proteome" all contribute to voids needing filled for genomics to work in a fast-paced clinical setting. The future will hold the tools to fill in these voids, with new data sets and the continual development of new technologies allowing for expansion of genomic medicine, ushering in the days to come for precision medicine. In this review we highlight these and other points in hopes of advancing and guiding precision medicine into the future for optimal success.

Perspectives of US private payers on insurance coverage for pediatric and prenatal exome sequencing: Results of a study from the Program in Prenatal and Pediatric Genomic Sequencing (P3EGS)

“…We plan to pursue this avenue by examining clinical utility from the broader perspective across CSER sites and stakeholders, and working with the Clinical Utility, Health Economics, and Policy (CUHEP) working group formed within the CSER consortium. 37 As the genomic field is likely to transition from exome to genome sequencing, 38 understanding payers' coverage considerations will become increasingly important. Genome sequencing may exacerbate payers' concerns about merit and utility in various diseases, and the risks and harms from VUS.…”

Dimensionality and Structure in Cancer Genomics: A Statistical Learning Perspective

“…For the study of cancer, a disease of the genome, the ability to rapidly and cheaply sequence normal and tumour-derived DNA has transformed basic research, birthing the field of cancer genomics. This is beginning to impact frontline clinical oncology [3]. Whole genome sequencing is not yet standard of care for the generic cancer patient, but access to in-depth genetic data is becoming more common.…”

Exome Sequencing and Molecular Diagnosis

“…Considering the steadily falling cost of ES and GS, researchers and physicians hope that affordable sequencing will lead to more personalized medical care in ways that will benefit children, families, and society (5). But does clinical genomics actually help patients and their families?…”