Next Generation Sequencing (NGS) technology is currently revolutionizing many fields of basic and medical research in the life sciences and genetic diagnosis in virtually every relevant context. As prices and turnaround times continue to decrease, NGS may soon replace many other genetic methods. The characterization of genetic variation in relation to drug disposition and drug response is, so to say, the essence of pharmacogenetics/genomics, and thus NGS will undoubtedly play an increasing role as a tool for discovery, analysis and diagnosis in this discipline as well. Currently a mishmash of methods based on PCR, mass spectrometry, Sanger sequencing and others are in use with often unknown conformity. NGS in its most common form is a multiplex technology that yields
billions of relatively short reads that are mapped and assembled to a reference genome, allowing discovery of new variants from SNPs and small InDels to large structural variation as well as reliable determination of known variants for diagnosis. Single-molecule sequencing on the other hand permits extremely long reads and determination of haplotypes that compromise several genes. RNA
sequencing (RNAseq) as another NGS application has opened the way to comprehensive and quantitative transcriptomics. NGS is flexible and scalable allowing not only unbiased global sequencing of the whole genome (WGS) but also focus on coding (exonic) sequences (WES) and almost any kind of customization. However, there are also limitations. Technological limitations exist, for example, with respect to the coverage and accuracy within certain genomic areas, or the mapping of short reads to genes with complex architecture like those that comprise pseudogenes (particularly important in pharmacogenetics/ genomics). Even more challenging will be the necessity to predict and assign functional consequences for the myriads of variants that will be detected in each study or in each patient. For clinical applications challenges are to provide fast, accurate and comprehensive genetic diagnosis and to pinpoint ways to use such high density data for defining and optimizing treatment options.
In this Research Topic, we want to explore the full potential of NGS in pharmacogenomics.
Contributions that relate to these or similar topics are welcome:
- whole genome sequencing (WGS) and whole exome sequencing (WES) in research and diagnosis
- NGS technologies in disease diagnostics in relation to treatment options and outcome
- customization and panel approaches for pharmacogenetics
- large structural variants and CNVs from NGS data
- single molecule sequencing and haplotyping
- mobile settings, e.g. for field research
- platform comparisons
- RNAseq applications in pharmacogenomics
- NGS to characterize somatic variation, particularly in cancer
- data management, storage and exploitation
- development of algorithms for genotype inference
- prediction and analysis of functional consequences
- translational approaches with bench to bedside benefits for patients
- analysis of epistatic interactions
- clinical implementation
- ethical, legal, and regulatory aspects related to NGS in pharmacogenetics/genomics
Next Generation Sequencing (NGS) technology is currently revolutionizing many fields of basic and medical research in the life sciences and genetic diagnosis in virtually every relevant context. As prices and turnaround times continue to decrease, NGS may soon replace many other genetic methods. The characterization of genetic variation in relation to drug disposition and drug response is, so to say, the essence of pharmacogenetics/genomics, and thus NGS will undoubtedly play an increasing role as a tool for discovery, analysis and diagnosis in this discipline as well. Currently a mishmash of methods based on PCR, mass spectrometry, Sanger sequencing and others are in use with often unknown conformity. NGS in its most common form is a multiplex technology that yields
billions of relatively short reads that are mapped and assembled to a reference genome, allowing discovery of new variants from SNPs and small InDels to large structural variation as well as reliable determination of known variants for diagnosis. Single-molecule sequencing on the other hand permits extremely long reads and determination of haplotypes that compromise several genes. RNA
sequencing (RNAseq) as another NGS application has opened the way to comprehensive and quantitative transcriptomics. NGS is flexible and scalable allowing not only unbiased global sequencing of the whole genome (WGS) but also focus on coding (exonic) sequences (WES) and almost any kind of customization. However, there are also limitations. Technological limitations exist, for example, with respect to the coverage and accuracy within certain genomic areas, or the mapping of short reads to genes with complex architecture like those that comprise pseudogenes (particularly important in pharmacogenetics/ genomics). Even more challenging will be the necessity to predict and assign functional consequences for the myriads of variants that will be detected in each study or in each patient. For clinical applications challenges are to provide fast, accurate and comprehensive genetic diagnosis and to pinpoint ways to use such high density data for defining and optimizing treatment options.
In this Research Topic, we want to explore the full potential of NGS in pharmacogenomics.
Contributions that relate to these or similar topics are welcome:
- whole genome sequencing (WGS) and whole exome sequencing (WES) in research and diagnosis
- NGS technologies in disease diagnostics in relation to treatment options and outcome
- customization and panel approaches for pharmacogenetics
- large structural variants and CNVs from NGS data
- single molecule sequencing and haplotyping
- mobile settings, e.g. for field research
- platform comparisons
- RNAseq applications in pharmacogenomics
- NGS to characterize somatic variation, particularly in cancer
- data management, storage and exploitation
- development of algorithms for genotype inference
- prediction and analysis of functional consequences
- translational approaches with bench to bedside benefits for patients
- analysis of epistatic interactions
- clinical implementation
- ethical, legal, and regulatory aspects related to NGS in pharmacogenetics/genomics
