Personalized Sequencing and the Future of Medicine: Discovery, Diagnosis and Defeat of Disease

F2: Prothrombin; F5: Factor V Leiden; Ph: Philadelphia.
Data taken from [32].

F2: Prothrombin; F5: Factor V Leiden.
Data taken from [32].

Authors and Disclosures

Edward D Esplin^‡,1, Ling Oei^‡,1 & Michael P Snyder*^,1

¹300 Pasteur Drive, Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA

*Author for correspondence
Tel.: +1 650 736 8099 mpsnyder@stanford.edu

^‡Authors contributed equally

Financial & competing interests disclosure
ED Esplin holds the Tashia and John Morgridge Endowed Postdoctoral Fellowship and is supported by the Child Health Research Institute and the Stanford CTSA grant UL1 TR000093. This work was supported by NIH grants (NIH National Center for Advancing Translational Sciences [NCATS] Grant UL1 TR000093 to ED Esplin and NIH National Institute of Diabetes and Digestive and Kidney Diseases [NIDDK] Grant U54 DK102556 to MP Snyder. MP Snyder serves as founder and consultant for Personalis, and is a member of the scientific advisory board of GenapSys and a consultant for Illumina. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.

Sidebar

Executive Summary

Background

• Personalized sequencing has advanced in scale, speed and affordability to become a powerful tool in the study of individuals and their diseases.

Cancer genome sequencing

• The diagnosis and management of various forms of cancer has benefited from two forms of personalized sequencing: tumor DNA and germline. These have enabled the beginning of individualized therapy of cancer.

Sequencing the unknown: rare diseases

• Rare and 'mystery' diseases as targets for personalized sequencing have yielded etiologies for previously undiagnosed diseases, in rare cases capacitating effective treatment.

Sequencing the 'healthy'

• At least one study analyzing the genomic sequence of a clinically healthy individual found a predisposition to diabetes, pharmacological interventions to which the individual would favorably respond, and allowed lifestyle changes to prevent the disease's onset.

• Several obstacles impede the current clinical application of personalized sequencing, one of which is the technological limitations of sequencing accuracy, where much progress is needed to allow transition to clinical medicine.

• Interpretation of the genomic sequence currently remains a significant impediment to clinical applications. While many approaches are under development, new in silico and in vitro strategies are critical to understanding genomic data with acuity sufficient for clinical decision-making.

• Variant(s) of unknown significance uncovered during sequencing will require additional interrogation via RNA expression, proteomic, metabolomic and other functional analyses, to facilitate accurate classification as benign and disease causing.

Sequencing patients: integration into clinical care

• An individual's personalized sequence may eventually become a valuable part of their electronic medical record, to be referenced periodically in the identification and management of disease.

Future perspective

• Personalized sequencing represents a major step toward a revolutionary future of disease treatment, prediction and prevention in the practice of medicine.