Emergence of single-molecule sequencing and potential for molecular diagnostic applications

Abstract

The effective demonstration of single-molecule sequencing at scale over the last several years offers the exciting opportunity for a new era in the field of molecular diagnostics. As we aim to personalize and deliver cost-effective healthcare, we must consider the need to fully integrate genomics into decision-making. We must be able to accurately and cost effectively obtain a complete genome sequence for disease diagnosis, interrogate a molecular signature from blood for therapeutic monitoring, obtain a tumor mutation profile for optimizing therapeutic choice – each molecular diagnostic measurement utilized to better inform patient care. Would a physician or molecular pathology laboratory want to utilize a PCR process in which millions of DNA copies of a patient’s nucleic acid are created when an alternative approach allowing direct measurement of the nucleic acids is possible? I would suggest not! In this article we will focus on the emergence of single-molecule sequencing, the single-molecule sequencing methodologies in the marketplace or under development today, as well as the importance of these methods for molecular characterization and diagnosis of disease with the ultimate application for molecular diagnostics.

Keywords::

• DNA
• microbial and viral screening
• nanopore
• noninvasive fetal screening
• quantitation
• real-time DNA sequencing
• RNA
• sequencing by synthesis
• single-molecule sequencing
• tumor genome

Acknowledgements

Special thanks to Patrick Terry for providing insight into the many principles and challenges of genomics and molecular diagnostics and all my colleagues at Helicos for their expertise and passion to achieve the vision described herein.

Financial & competing interests disclosure

Patrice M Milos is an employee of Helicos BioSciences Corporation, Cambridge, MA, USA. The author has 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.