Reducing the use of animal models in drug development and safety assessment has long been supported by the U.S.Food and Drug Administration(FDA).The report by Royal Society for the Prevention of Cruelty to Animals ind...Reducing the use of animal models in drug development and safety assessment has long been supported by the U.S.Food and Drug Administration(FDA).The report by Royal Society for the Prevention of Cruelty to Animals indicates that in 2020,experiments involved the use of over 100 million animals,with the United States leading the list by utilizing 20 million animals.Beyond ethical considerations associated with animal testing and the costs in terms of time and money,animal models are not always effective in predicting human reactions to drug exposure.While animal testing has been the traditional method for assessing the safety and efficacy of drugs.展开更多
High-throughput next generation sequencing (NGS) is a shotgun approach applied in a parallel fashion by which the genome is fragmented and sequenced through small pieces and then analyzed either by aligning to a known...High-throughput next generation sequencing (NGS) is a shotgun approach applied in a parallel fashion by which the genome is fragmented and sequenced through small pieces and then analyzed either by aligning to a known reference genome or by de novo assembly without reference genome.This technology has led researchers to conduct an explosion of sequencing related projects in multidisciplinary fields of science.However,due to the limitations of sequencing-based chemistry,length of sequencing reads and the complexity of genes,it is difficult to determine the sequences of some portions of the human genome,leaving gaps in genomic data that frustrate further analysis.Particularly,some complex genes are difficult to be accurately sequenced or mapped because they contain high GC-content and/or low complexity regions,and complicated pseudogenes,such as the genes encoding xenobiotic metabolizing enzymes and transporters (XMETs).The genetic variants in XMET genes are critical to predicate interindividual variability in drug efficacy,drug safety and susceptibility to environmental toxicity.We summarized and discussed challenges,wet-lab methods,and bioinformatics algorithms in sequencing "complex" XMET genes,which may provide insightful information in the application of NGS technology for implementation in toxicogenomics and pharmacogenomics.展开更多
文摘Reducing the use of animal models in drug development and safety assessment has long been supported by the U.S.Food and Drug Administration(FDA).The report by Royal Society for the Prevention of Cruelty to Animals indicates that in 2020,experiments involved the use of over 100 million animals,with the United States leading the list by utilizing 20 million animals.Beyond ethical considerations associated with animal testing and the costs in terms of time and money,animal models are not always effective in predicting human reactions to drug exposure.While animal testing has been the traditional method for assessing the safety and efficacy of drugs.
基金supported by the FDA Project(E0765001)the National Key Research and Development Program of China(2016YFC0902100 to Geng Chen)
文摘High-throughput next generation sequencing (NGS) is a shotgun approach applied in a parallel fashion by which the genome is fragmented and sequenced through small pieces and then analyzed either by aligning to a known reference genome or by de novo assembly without reference genome.This technology has led researchers to conduct an explosion of sequencing related projects in multidisciplinary fields of science.However,due to the limitations of sequencing-based chemistry,length of sequencing reads and the complexity of genes,it is difficult to determine the sequences of some portions of the human genome,leaving gaps in genomic data that frustrate further analysis.Particularly,some complex genes are difficult to be accurately sequenced or mapped because they contain high GC-content and/or low complexity regions,and complicated pseudogenes,such as the genes encoding xenobiotic metabolizing enzymes and transporters (XMETs).The genetic variants in XMET genes are critical to predicate interindividual variability in drug efficacy,drug safety and susceptibility to environmental toxicity.We summarized and discussed challenges,wet-lab methods,and bioinformatics algorithms in sequencing "complex" XMET genes,which may provide insightful information in the application of NGS technology for implementation in toxicogenomics and pharmacogenomics.
