The publisher's final edited version of this article is available at Expert Opin Drug Discov See other articles in PMC that cite the published article. Furthermore, drug mechanism of action and biomarkers to predict drug efficacy and safety need to be identified for effective design of clinical trials, decreasing attrition rates, regulatory agency approval process and drug repositioning.
By expanding the power of genetics and pharmacogenetics studies, next generation nucleic acid sequencing technologies have started to play an important role in all stages of drug discovery.
Areas covered This article reviews the first and second generation sequencing technologies SGSTs and challenges they pose to biomedicine.
The Big Data Era has Arrived
The article then focuses on the emerging third generation sequencing technologies TGSTstheir technological foundations and potential contributions to drug discovery.
Expert Opinion Despite the scientific and commercial success of SGSTs, the goal of rapid, comprehensive and unbiased sequencing of nucleic acids has not been achieved. TGSTs promise to increase sequencing throughput and read lengths, decrease costs, run times and error rates, single-cell messenger rna sequencing reveals rare biases inherent in SGSTs, and offer capabilities beyond nucleic acid sequencing.
Such changes will have positive impact in all sequencing applications to drug discovery. Keywords: Drug discovery, Epigenetics, Genetics, Next generation sequencing, Pharmacogenetics, Third generation sequencing 1.
Despite these recent successes, the sequencing of the human genome did not bring the much anticipated revolution and productivity rise in drug discovery. Challenges in drug discovery extend well beyond discovery and validation of targets.
Here we report the first identification of a bacterial symbiont in the testate amoeba Cochliopodium.
Drug mechanism of action and biomarkers to predict drug efficacy and safety need to be identified for the purposes of effective design of clinical trials, decreasing attrition rates, regulatory agency approval process and drug repositioning to other disease conditions [ 23 ].
Today, drug companies face diminishing research and development productivity, increasingly strict regulatory requirements, key patent expirations and payers requiring decreased costs [ 3 ].
The pressures due to these challenges are rapidly increasing and already at a point which prompted several prominent thought-leaders to question the survival of the drug industry [ 4 ]. To maintain profitability, drug companies need to decrease attrition rates, reduce time and costs of clinical trials, form a healthy drug pipeline and develop processes to maximize success and efficiency in each phase of the drug discovery process, from the early target-to-hit phase to product launch and postmarketing surveillance.
Due to the enabling nature of technology in drug discovery, benefiting from the latest technological advances is necessary to maximize drug development efficiency. During the last decade, microarray technologies have become integrated into the drug development process primarily due to their ability to monitor global gene expression levels and to enable investigations of the causative genetic states through genome-wide association studies GWAS [ 5 ].
Origins of systems approaches in drug discovery owe much of their progress to the comprehensive profiles generated with microarray-based technologies [ 6 ]. This review will briefly summarize the current state of SGSTs, and focus on third generation sequencing technologies TGSTs and benefits they may bring to drug discovery process over existing technologies.
- Genotypisierung Publikationen Autoren: Goethe,E.
- The publisher's final edited version of this article is available at Trends Mol Med See other articles in PMC that cite the published article.
- Der Schlüssel zum Verständnis der Funktion eines Organs ist die Kenntnis der unterschiedlichen Zelltypen, die ihrerseits verschiedene Funktionen ausüben, und ihrer Entwicklungswege, beginnend bei sogenannten Stammzellen.
- Die Variabilität der Genexpression kann vielfältige Ursachen haben.
- Publikationen | Forschung | Helmholtz-Zentrum für Infektionsforschung
These SGSTs generate hundreds of thousands to billions of 25— nucleotide-long reads within days in a low-cost manner compared to Sanger sequencing. Recent reviews describe the technological foundations and working principles of these technologies [ 1314 ].
In this review, we summarize the physiological background from genes via transcriptome to proteins and metabolites and discuss the variety of dimensions in which a biological entity may be studied.