TY - JOUR
T1 - Clinical massively parallel sequencing
AU - Gao, Ge
AU - Smith, David I.
N1 - Funding Information:
The authors thank Illumina, Oxford Nanopore, Pacific Bioscience, and BGI for providing images for the illustration of different sequencing technologies.
Publisher Copyright:
© 2019 American Association for Clinical Chemistry
PY - 2020
Y1 - 2020
N2 - BACKGROUND: The newest advances in DNA sequencing are based on technologies that perform massively parallel sequencing (MPS). Since 2006, the output from MPS platforms has increased from 20 Mb to >7 Tb. First-generation MPS platforms amplify individual DNA molecules to multiple copies and then interrogate the sequence of those molecules. Second-generation MPS analyzes single unamplified molecules to generate much longer sequence reads but with less output than first-generation MPS and lower first-pass accuracy. With MPS technologies, it is now possible to analyze genomes, exomes, a defined subset of genes, transcriptomes, and even methylation across the genome. These technologies have and will continue to completely transform the clinical practice. CONTENT: The major first- and second-generation MPS platforms and how they are used in clinical practice are discussed. SUMMARY: The ability to sequence terabases of DNA per run on an MPS platform will dramatically change how DNA sequencing is used in clinical practice. Currently, MPS of targeted gene panels is the most common use of this technology clinically, but as the cost for genome sequencing inches downward to $100, this may soon become the method of choice (with the caveat that, at least in the near term, clinical-grade genome sequencing with interpretation may cost much more than $100). Other uses of this technology include sequencing of a mixture of bacterial and viral species (metagenomics), as well as the characterization of methylation across the genome.
AB - BACKGROUND: The newest advances in DNA sequencing are based on technologies that perform massively parallel sequencing (MPS). Since 2006, the output from MPS platforms has increased from 20 Mb to >7 Tb. First-generation MPS platforms amplify individual DNA molecules to multiple copies and then interrogate the sequence of those molecules. Second-generation MPS analyzes single unamplified molecules to generate much longer sequence reads but with less output than first-generation MPS and lower first-pass accuracy. With MPS technologies, it is now possible to analyze genomes, exomes, a defined subset of genes, transcriptomes, and even methylation across the genome. These technologies have and will continue to completely transform the clinical practice. CONTENT: The major first- and second-generation MPS platforms and how they are used in clinical practice are discussed. SUMMARY: The ability to sequence terabases of DNA per run on an MPS platform will dramatically change how DNA sequencing is used in clinical practice. Currently, MPS of targeted gene panels is the most common use of this technology clinically, but as the cost for genome sequencing inches downward to $100, this may soon become the method of choice (with the caveat that, at least in the near term, clinical-grade genome sequencing with interpretation may cost much more than $100). Other uses of this technology include sequencing of a mixture of bacterial and viral species (metagenomics), as well as the characterization of methylation across the genome.
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U2 - 10.1373/clinchem.2019.303305
DO - 10.1373/clinchem.2019.303305
M3 - Article
C2 - 31811004
AN - SCOPUS:85077655107
SN - 0009-9147
VL - 66
SP - 77
EP - 88
JO - Clinical chemistry
JF - Clinical chemistry
IS - 1
ER -