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Expert Review of Molecular Diagnostics May 2017The advent of next-generation sequencing (NGS) has introduced an exciting new era in biomedical research. NGS forms the foundation of current genetic testing approaches,... (Review)
Review
The advent of next-generation sequencing (NGS) has introduced an exciting new era in biomedical research. NGS forms the foundation of current genetic testing approaches, including targeted gene panel testing, as well as more comprehensive whole-exome and whole-genome sequencing. Together, these approaches promise to provide critical insights into the understanding of health and disease. However, with NGS testing come many ethical questions and concerns, particularly when testing involves children. These concerns are especially relevant for children with cancer, where the testing of tumor and germline tissues is increasingly being incorporated into clinical care. Areas covered: In this manuscript, we explore the key ethical considerations related to conducting germline NGS testing in pediatric oncology, focusing on the four main principles of beneficence, non-maleficence, autonomy and justice. Expert commentary: The ethical issues surrounding germline NGS testing are complex and result in part from our limited understanding of the medical relevance of many of the results obtained and poor knowledge of the impacts of testing, both beneficial and detrimental, on patients and their families. In this article we discuss the risks and benefits of germline NGS testing and the arguments for and against such testing in children with cancer.
Topics: Adolescent; Child; Child, Preschool; Ethics; Female; Germ-Line Mutation; High-Throughput Nucleotide Sequencing; Humans; Infant; Male; Neoplasms
PubMed: 28399664
DOI: 10.1080/14737159.2017.1316665 -
Nature Reviews. Genetics Apr 2018Developments in next-generation sequencing technologies have driven the clinical application of diagnostic tests that interrogate the whole genome, which offer the... (Review)
Review
Developments in next-generation sequencing technologies have driven the clinical application of diagnostic tests that interrogate the whole genome, which offer the chance to diagnose rare inherited diseases or inform the targeting of therapies. New genomic diagnostic tests compete with traditional approaches to diagnosis, including the genetic testing of single genes and other clinical strategies, for finite health-care budgets. In this context, decision analytic model-based cost-effectiveness analysis is a useful method to help evaluate the costs versus consequences of introducing new health-care interventions. This Perspective presents key methodological, technical, practical and organizational challenges that must be considered by decision-makers responsible for the allocation of health-care resources to obtain robust and timely information about the relative cost-effectiveness of the increasing numbers of emerging genomic tests.
Topics: Cost-Benefit Analysis; Genetic Testing; Genomics; High-Throughput Nucleotide Sequencing; Humans
PubMed: 29353875
DOI: 10.1038/nrg.2017.108 -
Forensic Science International. Genetics Sep 2015It has been almost a decade since the first next generation sequencing (NGS) technologies emerged and quickly changed the way genetic research is conducted. Today, full... (Review)
Review
It has been almost a decade since the first next generation sequencing (NGS) technologies emerged and quickly changed the way genetic research is conducted. Today, full genomes are mapped and published almost weekly and with ever increasing speed and decreasing costs. NGS methods and platforms have matured during the last 10 years, and the quality of the sequences has reached a level where NGS is used in clinical diagnostics of humans. Forensic genetic laboratories have also explored NGS technologies and especially in the last year, there has been a small explosion in the number of scientific articles and presentations at conferences with forensic aspects of NGS. These contributions have demonstrated that NGS offers new possibilities for forensic genetic case work. More information may be obtained from unique samples in a single experiment by analyzing combinations of markers (STRs, SNPs, insertion/deletions, mRNA) that cannot be analyzed simultaneously with the standard PCR-CE methods used today. The true variation in core forensic STR loci has been uncovered, and previously unknown STR alleles have been discovered. The detailed sequence information may aid mixture interpretation and will increase the statistical weight of the evidence. In this review, we will give an introduction to NGS and single-molecule sequencing, and we will discuss the possible applications of NGS in forensic genetics.
Topics: Forensic Genetics; High-Throughput Nucleotide Sequencing; Humans; Microsatellite Repeats; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Sequence Analysis, DNA
PubMed: 25704953
DOI: 10.1016/j.fsigen.2015.02.002 -
Annual Review of Biomedical Data Science Aug 2023The human microbiome is complex, variable from person to person, essential for health, and related to both the risk for disease and the efficacy of our treatments. There... (Review)
Review
The human microbiome is complex, variable from person to person, essential for health, and related to both the risk for disease and the efficacy of our treatments. There are robust techniques to describe microbiota with high-throughput sequencing, and there are hundreds of thousands of already-sequenced specimens in public archives. The promise remains to use the microbiome both as a prognostic factor and as a target for precision medicine. However, when used as an input in biomedical data science modeling, the microbiome presents unique challenges. Here, we review the most common techniques used to describe microbial communities, explore these unique challenges, and discuss the more successful approaches for biomedical data scientists seeking to use the microbiome as an input in their studies.
Topics: Humans; Microbiota; Precision Medicine; High-Throughput Nucleotide Sequencing
PubMed: 37159872
DOI: 10.1146/annurev-biodatasci-020722-043017 -
Current Issues in Molecular Biology 2018Next-generation sequencing technologies are revolutionizing biology by permitting, transcriptome sequencing, whole-genome sequencing and resequencing, and genome-wide... (Review)
Review
Next-generation sequencing technologies are revolutionizing biology by permitting, transcriptome sequencing, whole-genome sequencing and resequencing, and genome-wide single nucleotide polymorphism profiling. Orchid research has benefited from this breakthrough, and a few orchid genomes are now available; new biological questions can be approached and new breeding strategies can be designed. The first part of this review describes the unique features of orchid biology. The second part provides an overview of the current next-generation sequencing platforms, many of which are already used in plant laboratories. The third part summarizes the state of orchid transcriptome and genome sequencing and illustrates current achievements. The genetic sequences currently obtained will not only provide a broad scope for the study of orchid biology, but also serves as a starting point for uncovering the mystery of orchid evolution.
Topics: Biological Evolution; Chromosome Mapping; DNA, Plant; Gene Expression Profiling; Genome, Plant; High-Throughput Nucleotide Sequencing; Orchidaceae; Plant Breeding; Polymorphism, Single Nucleotide; Sequence Analysis, DNA; Transcriptome
PubMed: 28885174
DOI: 10.21775/cimb.027.051 -
Methods in Molecular Biology (Clifton,... 2021Normalization is an important step in the analysis of single-cell RNA-seq data. While no single method outperforms all others in all datasets, the choice of...
Normalization is an important step in the analysis of single-cell RNA-seq data. While no single method outperforms all others in all datasets, the choice of normalization can have profound impact on the results. Data-driven metrics can be used to rank normalization methods and select the best performers. Here, we show how to use R/Bioconductor to calculate normalization factors, apply them to compute normalized data, and compare several normalization approaches. Finally, we briefly show how to perform downstream analysis steps on the normalized data.
Topics: Animals; Computational Biology; Gene Expression Profiling; High-Throughput Nucleotide Sequencing; Humans; Quality Control; RNA-Seq; Reference Standards; Sequence Analysis, RNA; Single-Cell Analysis; Software; Transcriptome; Exome Sequencing
PubMed: 33835450
DOI: 10.1007/978-1-0716-1307-8_17 -
British Journal of Cancer Feb 2017In the context of solid tumours, the evolution of cancer therapies to more targeted and nuanced approaches has led to the impetus for personalised medicine. The targets... (Review)
Review
In the context of solid tumours, the evolution of cancer therapies to more targeted and nuanced approaches has led to the impetus for personalised medicine. The targets for these therapies are largely based on the driving genetic mutations of the tumours. To track these multiple driving mutations the use of next generation sequencing (NGS) coupled with a morphomolecular approach to tumours, has the potential to deliver on the promises of personalised medicine. A review of NGS and its application in a universal healthcare (UHC) setting is undertaken as the technology has a wide appeal and utility in diagnostic, clinical trial and research paradigms. Furthermore, we suggest that these can be accommodated with a unified integromic approach. Challenges remain in bringing NGS to routine clinical use and these include validation, handling of the large amounts of information flow and production of a clinically useful report. These challenges are particularly acute in the setting of UHC where tests are not reimbursed and there are finite resources available. It is our opinion that the challenges faced in applying NGS in a UHC setting are surmountable and we outline our approach for its routine application in diagnostic, clinical trial and research paradigms.
Topics: Clinical Trials as Topic; High-Throughput Nucleotide Sequencing; Humans; Insurance, Health; Mutation; Neoplasms; Precision Medicine; Sequence Analysis, DNA
PubMed: 28103613
DOI: 10.1038/bjc.2016.452 -
Briefings in Bioinformatics Jan 2021The study of microbial communities crucially relies on the comparison of metagenomic next-generation sequencing data sets, for which several methods have been designed... (Review)
Review
The study of microbial communities crucially relies on the comparison of metagenomic next-generation sequencing data sets, for which several methods have been designed in recent years. Here, we review three key challenges in the comparison of such data sets: species identification and quantification, the efficient computation of distances between metagenomic samples and the identification of metagenomic features associated with a phenotype such as disease status. We present current solutions for such challenges, considering both reference-based methods relying on a database of reference genomes and reference-free methods working directly on all sequencing reads from the samples.
Topics: Animals; High-Throughput Nucleotide Sequencing; Humans; Metagenomics; Microbiota
PubMed: 32577746
DOI: 10.1093/bib/bbaa121 -
The Journal of Investigative Dermatology May 2017Like any true conceptual revolution, next-generation sequencing (NGS) has not only radically changed research and clinical practice, it has also modified scientific... (Review)
Review
Like any true conceptual revolution, next-generation sequencing (NGS) has not only radically changed research and clinical practice, it has also modified scientific culture. With the possibility to investigate DNA contents of any organism and in any context, including in somatic disorders or in tissues carrying complex microbial populations, it initially seemed as if the genetic underpinning of any biological phenomenon could now be deciphered in an almost streamlined fashion. However, over the past recent years, we have once again come to understand that there is no such a thing as great opportunities without great challenges. The steadily expanding use of NGS and related applications is now facing biologists and physicians with novel technological obstacles, analytical hurdles and increasingly pressing ethical questions.
Topics: High-Throughput Nucleotide Sequencing; Humans; Molecular Biology; Skin; Skin Diseases
PubMed: 28411851
DOI: 10.1016/j.jid.2016.02.818 -
PLoS Computational Biology Feb 2021
Topics: Computational Biology; High-Throughput Nucleotide Sequencing; Humans; Software; Terminology as Topic; Whole Genome Sequencing; Writing
PubMed: 33600404
DOI: 10.1371/journal.pcbi.1008645