Translating the power of high-throughput sequencing technologies from the research sphere into the clinic is a current major focus for many health-care providers and researchers, and the power of these technologies is being harnessed to address an increasingly diverse range of problems. Excitingly, real benefits for patients are starting to emerge. The scale and efficiency of sequencing that can now be achieved is providing unprecedented progress in areas from infectious disease and cancer, to common and rare genetic disorders and pre-natal testing.

High-profile successes in the application of next-generation sequencing in the clinic include using sequencing to follow the spread of infections, and uncovering the genetic basis of inherited diseases, such as the molecular mechanisms underlying renal developmental disorders and ciliopathies. In addition, sequencing is informing clinical diagnostics and could be used to classify cancer sub-types for appropriate therapies.

We are at an exciting time in genomics when, after years of studies amassing a wealth of information on the genetic susceptibility to disease, decisive steps can be taken towards translating these findings to clinical care. At this critical turning point, this collection highlights the breadth of applications of next-generation sequencing technologies in the clinic and the importance of the insights that are being gained through these methods to improve health.

All content for this collection has been chosen by the editors of Nature Reviews Genetics, and the collection has been made freely available for 6 months thanks to support from Life Technologies, a brand of Thermo Fisher Scientific.

Image credit: Lonely_/iStock/Thinkstock



NEWS & ANALYSIS

Next-generation sequencing: does the next generation still have a right to an open future?

Annelien L. Bredenoord, Martine C. de Vries & Johannes J. M. van Delden

doi:10.1038/nrg3459

Nature Reviews Genetics 14, 306 (2013)

Sherlock Genomes — viral investigator

Sarah E. Smith & Rachael S. Wash

doi:10.1038/nrmicro2979

Nature Reviews Microbiology 11, 150 (2013)

Genomic polish for shoe-leather epidemiology

Steven Y. C. Tong

doi:10.1038/nrmicro2935

Nature Reviews Microbiology 11, 8 (2013)

Bringing RNA-seq closer to the clinic

Kendall Van Keuren-Jensen, Jonathan J Keats & David W Craig

doi:10.1038/nbt.3017

Nature Biotechnology 32, 884-885 (2014)

Next-generation sequencing in the clinic

Jason Y Park, Larry J Kricka & Paolo Fortina

doi:10.1038/nbt.2743

Nature Biotechnology 31, 990-992 (2013)

Genomic testing reaches into the womb

Malorye Allison

doi:10.1038/nbt.2627

Nature Biotechnology 31, 595-601 (2013)

Genetics: Utility of next-generation sequencing in ataxias

Eng-King Tan

doi:10.1038/nrneurol.2013.212

Nature Reviews Neurology 9, 614-615 (2013)

PROGRESS

High-throughput bacterial genome sequencing: an embarrassment of choice, a world of opportunity

Nicholas J. Loman, Chrystala Constantinidou, Jacqueline Z. M. Chan, Mihail Halachev, Martin Sergeant, Charles W. Penn, Esther R. Robinson & Mark J. Pallen

doi:10.1038/nrmicro2850

Nature Reviews Microbiology 10, 599-606 (2012)

In this Progress article, Pallen, Loman and colleagues present a snapshot of the high-throughput sequencing platforms available to microbiologists today, together with the relevant analytical tools, and evaluate their strengths and weaknesses in obtaining bacterial genome sequences.

REVIEWS

Next-generation sequencing for research and diagnostics in kidney disease

Kirsten Y. Renkema, Marijn F. Stokman, Rachel H. Giles & Nine V. A. M. Knoers

doi:10.1038/nrneph.2014.95

Nature Reviews Nephrology 10, 433-444 (2014)

The introduction of next-generation sequencing has provided revolutionary opportunities for comprehensive genetic testing in research and diagnostics. Here, the authors discuss approaches used for novel gene identification, the potential of these techniques to improve the management of patients with inherited kidney diseases—focusing on nephronophthisis and congenital anomalies of the kidney and urinary tract—and the remaining challenges for implementation of next-generation sequencing in clinical practice.

Exploration of liver cancer genomes

Tatsuhiro Shibata & Hiroyuki Aburatani

doi:10.1038/nrgastro.2014.6

Nature Reviews Gastroenterology & Hepatology 11, 340-349 (2014)

Advances in sequencing technologies have enabled the examination of liver cancer genomes at high resolution. The authors of this Review discuss somatic mutations, structural alterations, HBV integration, RNA editing and retrotransposon changes associated with liver cancer. Potential therapeutic targets are also highlighted.

Molecular genetic testing and the future of clinical genomics

Sara Huston Katsanis & Nicholas Katsanis

doi:10.1038/nrg3493

Nature Reviews Genetics 14, 415-426 (2013)

The authors review current technologies for clinical genetic testing. Moves are being made towards whole-genome and whole-exome sequencing in the clinic, although other technologies will continue to be of value.

Cancer genome-sequencing study design

Jill C. Mwenifumbo & Marco A. Marra

doi:10.1038/nrg3445

Nature Reviews Genetics 14, 321-332 (2013)

This Review discusses the considerations for designing cancer genome-sequencing studies to fulfil different study aims, such as detecting recurrent mutations or assessing clonal evolution. For example, the cohort type and depth of sequencing can influence the downstream analysis.

The expanding scope of DNA sequencing

Jay Shendure & Erez Lieberman Aiden

doi:10.1038/nbt.2421

Nature Biotechnology 30, 1084-1094 (2012)

The authors consider applications that have been made possible by recent advances in DNA sequencing technology and provide guidance for experimental design and the development of new sequencing applications. They identify building blocks that are common to many sequencing-based experimental strategies and consider how best to incorporate sequencing technologies into a variety of experimental approaches.

Pharmacogenomics in clinical practice and drug development

Andrew R Harper & Eric J Topol

doi:10.1038/nbt.2424

Nature Biotechnology 30, 1117-1124 (2012)

In this Review, the authors argue that genomic guidance should be embedded in all drug development and treatment programs. Furthermore, they posit that genomics should guide research into all commonly used medications in clinical practice to improve efficacy, avoid serious adverse effects and promote cost effectiveness.

Transforming clinical microbiology with bacterial genome sequencing

Xavier Didelot, Rory Bowden, Daniel J. Wilson, Tim E. A. Peto & Derrick W. Crook

doi:10.1038/nrg3226

Nature Reviews Genetics 13, 601-612 (2012)

This Review sets out the emerging potential of next-generation sequencing in the context of clinical microbiology. Using bacterial genome sequencing as an example, the authors discuss the options and challenges for species identification, testing for virulence and drug resistance and monitoring outbreaks.

Whole-genome and whole-exome sequencing in neurological diseases

Jia-Nee Foo, Jian-Jun Liu & Eng-King Tan

doi:10.1038/nrneurol.2012.148

Nature Reviews Neurology 8, 508-517 (2012)

Next-generation sequencing approaches are becoming increasingly affordable for use in the clinical setting, and have the potential to provide valuable insights into the genetic underpinnings of complex neurological diseases. In this Review, Foo et al. discuss how whole-genome and whole-exome sequencing data can be deciphered, and consider how such data might be used for diagnosis and risk prediction in the neurology clinic.

PERSPECTIVES

Bacterial genome sequencing in the clinic: bioinformatic challenges and solutions

W. Florian Fricke & David A. Rasko

doi:10.1038/nrg3624

Nature Reviews Genetics 15, 49-55 (2014)

Bacterial whole-genome sequencing is showing promise in clinical applications. Here, the authors present their opinions on what the main bioinformatic challenges are in transferring bacterial whole-genome sequencing to medical diagnostics.

Implementing personalized cancer genomics in clinical trials

Richard Simon & Sameek Roychowdhury

doi:10.1038/nrd3979

Nature Reviews Drug Discovery 12, 358-369 (2013)

Rapid advances in next-generation sequencing (NGS) are facilitating deeper insights into the molecular classifications of cancer and the mechanisms of resistance development, thereby paving the way for a new era of personalized medicine. In this Perspective, Simon and Roychowdhury explore how genomic information can be used in the design of clinical trials for molecularly targeted anticancer drugs as well as for the development of new biomarkers.

Disease-targeted sequencing: a cornerstone in the clinic

Heidi L. Rehm

doi:10.1038/nrg3463

Nature Reviews Genetics 14, 295-300 (2013)

Clinical sequencing tests that focus on genes linked to specific diseases or phenotypes are increasingly widely being used. This article discusses how disease-targeting tests retain several advantages despite moves towards the clinical application of whole-genome or exome sequencing.

Next-generation sequencing in the clinic: are we ready?

Leslie G. Biesecker, Wylie Burke, Isaac Kohane, Sharon E. Plon & Ron Zimmern

doi:10.1038/nrg3357

Nature Reviews Genetics 13, 818-824 (2012)

We asked five experts their opinions on issues that arise from new clinical tests that are based on next-generation sequencing. Crucial gaps in infrastructure need to be addressed for the results of these tests to be optimally handled.

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