Sequencing XMET genes to promote genotype-guided risk assessment and precision medicine.

Computational Biology Gene Expression Regulation, Developmental Genome, Human Genotype High-Throughput Nucleotide Sequencing / methods Humans Membrane Transport Proteins / metabolism Precision Medicine Promoter Regions, Genetic Risk Assessment Sequence Analysis, DNA / methods Xenobiotics / metabolism
next generation sequencing pharmacogenomics precision medicine toxicogenomics xenobiotic metabolizing enzymes and transporters

Journal

Science China. Life sciences
ISSN: 1869-1889
Titre abrégé: Sci China Life Sci
Pays: China
ID NLM: 101529880

Informations de publication

Date de publication:
Jul 2019
Historique:
received: 05 11 2018
accepted: 06 12 2018
pubmed: 23 5 2019
medline: 25 4 2020
entrez: 23 5 2019
Statut: ppublish

Résumé

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 inter-individual 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.

Identifiants

DOI: 10.1007/s11427-018-9479-5 PMID: 31114935 PMC: PMC6612563
pubmed: 31114935
doi: 10.1007/s11427-018-9479-5
pii: 10.1007/s11427-018-9479-5
pmc: PMC6612563
mid: NIHMS1031940
doi:

Substances chimiques

Membrane Transport Proteins 0
Xenobiotics 0

Types de publication

Journal Article Review

Langues

eng

Sous-ensembles de citation

IM

Pagination

895-904

Subventions

Organisme : Intramural FDA HHS
ID : FD999999
Pays : United States

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Auteurs

Yaqiong Jin (Y)

Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, China.

Geng Chen (G)

Center for Bioinformatics and Computational Biology, and the Institute of Biomedical Sciences, Shanghai Key Laboratory of Regulatory Biology, the Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China.

Wenming Xiao (W)

National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR, 72079, USA.

Huixiao Hong (H)

National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR, 72079, USA.

Joshua Xu (J)

National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR, 72079, USA.

Yongli Guo (Y)

Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, China.

Wenzhong Xiao (W)

Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA.

Tieliu Shi (T)

Center for Bioinformatics and Computational Biology, and the Institute of Biomedical Sciences, Shanghai Key Laboratory of Regulatory Biology, the Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China.

Leming Shi (L)

State Key Laboratory of Genetic Engineering, School of Life Sciences and Cancer Center; Collaborative Innovation Center for Genetics and Development, Fudan University, Shanghai, 200433, China.

Weida Tong (W)

National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR, 72079, USA.

Baitang Ning (B)

National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR, 72079, USA. baitang.ning@fda.hhs.gov.

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