Why is genome sequencing important




















Genomic surveillance allows researchers to examine the genome sequence of the viral strains infecting the population. As the virus multiplies inside human cells, it needs to copy its genome to make more viral particles, a process called replication. Copying errors are sometimes introduced in this process because the enzyme that copies the RNA is error-prone. These copying errors introduce mutations or changes to the genomic sequence.

The changes alter the viral genes, leading to a change in the viral proteins encoded by them. Thus, though mutations arise in the normal course of viral replication, they can then get selected for their beneficial properties to the virus. Continuous monitoring of viral genome variations is very useful in tracing the path of the spread of the disease.

Such information can be very useful in containment measures and strategies. Metagenomic sequencing is most appropriate for diagnostic sequencing of unknown or poorly characterized viruses, PCR amplicon sequencing works well for short viral genomes and low diversity in primer binding sites, and target enrichment works for all pathogen sizes but is particularly advantageous for large viruses and for viruses that have diverse but well-characterized genomes. Two obvious areas of innovation currently exist: methods that can effectively deplete host DNA without affecting viral DNA, and the further development of long-read technologies to achieve the flexibility and competitive pricing of short-read technologies.

New technologies are required to unite the strengths of these different methods and enable healthcare providers to invest in a single technology that is suitable for all viral WGS applications. Gardner, R. The complete nucleotide sequence of an infectious clone of cauliflower mosaic virus by M13mp7 shotgun sequencing. Nucleic Acids Res. Lander, E. Initial sequencing and analysis of the human genome. Nature , — CAS Google Scholar. Fleischmann, R. Whole-genome random sequencing and assembly of Haemophilus influenzae Rd.

Science , — Fraser, C. The minimal gene complement of Mycoplasma genitalium. Hayden, E. Google Scholar. Turnbaugh, P.

The human microbiome project. Grigoriev, I. MycoCosm portal: gearing up for fungal genomes. Worthey, E. Making a definitive diagnosis: successful clinical application of whole exome sequencing in a child with intractable inflammatory bowel disease. Bryant, J. Whole-genome sequencing to identify transmission of Mycobacterium abscessus between patients with cystic fibrosis: a retrospective cohort study.

Lancet , — Lamelas, A. Emergence of a new epidemic Neisseria meningitidis serogroup A clone in the African meningitis belt: high-resolution picture of genomic changes that mediate immune evasion. Zaraket, H. Houldcroft, C. Detection of low frequency multi-drug resistance and novel putative maribavir resistance in immunocompromised pediatric patients with cytomegalovirus.

Witney, A. Clinical application of whole-genome sequencing to inform treatment for multidrug-resistant tuberculosis cases. Simen, B. Low-abundance drug-resistant viral variants in chronically HIV-infected, antiretroviral treatment-naive patients significantly impact treatment outcomes. Smith, G. Origins and evolutionary genomics of the swine-origin H1N1 influenza A epidemic. Gire, S. Genomic surveillance elucidates Ebola virus origin and transmission during the outbreak.

Koser, C. Routine use of microbial whole-genome sequencing in diagnostic and public health microbiology. PLoS Pathog. Cartwright, E. Microbial sequences benefit health now. Nature , Paredes, R. Clinical management of HIV-1 resistance. Antiviral Res. Van Laethem, K. HIV-1 genotypic drug resistance testing: digging deep, reaching wide?

Durant, J. Clevenbergh, P. The Viradapt Study: week 48 follow-up. Khudyakov, Y. Molecular surveillance of hepatitis C.

Kim, J. Molecular diagnosis and treatment of drug-resistant hepatitis B virus. World J. McGinnis, J. Next generation sequencing for whole genome analysis and surveillance of influenza A viruses.

Pawlotsky, J. Hepatitis C virus resistance to direct-acting antiviral drugs in interferon-free regimens. Gastroenterology , 70—86 Thomson, E. Comparison of next generation sequencing technologies for the comprehensive assessment of full-length hepatitis C viral genomes. Brunnemann, A. Drug resistance of clinical varicella-zoster virus strains confirmed by recombinant thymidine kinase expression and by targeted resistance mutagenesis of a cloned wild-type isolate. Agents Chemother. Karamitros, T.

De novo assembly of human herpes virus type 1 HHV-1 genome, mining of non-canonical structures and detection of novel drug-resistance mutations using short- and long-read next generation sequencing technologies. Piret, J. Antiviral drug resistance in herpesviruses other than cytomegalovirus. Melendez, D. Letermovir and inhibitors of the terminase complex: a promising new class of investigational antiviral drugs against human cytomegalovirus.

Drug Resist. Lassalle, F. Islands of linkage in an ocean of pervasive recombination reveals two-speed evolution of human cytomegalovirus genomes. Virus Evol. Lanier, E. Analysis of mutations in the gene encoding cytomegalovirus DNA polymerase in a phase 2 clinical trial of brincidofovir prophylaxis. Kaverin, N. Epitope mapping of the hemagglutinin molecule of a highly pathogenic H5N1 influenza virus by using monoclonal antibodies.

Franco, S. Detection of a sexually transmitted hepatitis C virus protease inhibitor-resistance variant in a human immunodeficiency virus-infected homosexual man. Gastroenterology , — Fujisaki, S. Outbreak of infections by hepatitis B virus genotype A and transmission of genetic drug resistance in patients coinfected with HIV-1 in Japan. Pierucci, P. Novel autologous T-cell therapy for drug-resistant cytomegalovirus disease after lung transplantation.

Heart Lung Transplant. Agoti, C. Local evolutionary patterns of human respiratory syncytial virus derived from whole-genome sequencing. Quick, J. Real-time, portable genome sequencing for Ebola surveillance. Aanensen, D. Whole-genome sequencing for routine pathogen surveillance in public health: a population snapshot of invasive Staphylococcus aureus in Europe. Faria, N. Zika virus in the Americas: early epidemiological and genetic findings. Mbisa, J. Evidence of self-sustaining drug resistant HIV-1 lineages among untreated patients in the United Kingdom.

Bartha, I. A genome-to-genome analysis of associations between human genetic variation, HIV-1 sequence diversity, and viral control. Power, R.

Genome-wide association study of HIV whole genome sequences validated using drug resistance. Cuevas, J. Extremely high mutation rate of HIV-1 in vivo. PLoS Biol. Vandenhende, M. Prevalence and evolution of low frequency HIV drug resistance mutations detected by ultra deep sequencing in patients experiencing first line antiretroviral therapy failure. Zhou, B. Composition and interactions of hepatitis B virus quasispecies defined the virological response during telbivudine therapy.

Itakura, J. Resistance-associated NS5A variants of hepatitis C virus are susceptible to interferon-based therapy. Rogers, M. Intrahost dynamics of antiviral resistance in influenza A virus reflect complex patterns of segment linkage, reassortment, and natural selection. Swenson, L. Next-generation sequencing to assess HIV tropism. Hutter, G. Kordelas, L. Coaquette, A. Mixed cytomegalovirus glycoprotein B genotypes in immunocompromised patients.

Solmone, M. Use of massively parallel ultradeep pyrosequencing to characterize the genetic diversity of hepatitis B virus in drug-resistant and drug-naive patients and to detect minor variants in reverse transcriptase and hepatitis B S antigen. Chou, S. Improved detection of emerging drug-resistant mutant cytomegalovirus subpopulations by deep sequencing. Fonager, J. Identification of minority resistance mutations in the HIV-1 integrase coding region using next generation sequencing.

Kyeyune, F. Low-frequency drug resistance in HIV-infected Ugandans on antiretroviral treatment is associated with regimen failure. Liu, P. Direct sequencing and characterization of a clinical isolate of Epstein—Barr virus from nasopharyngeal carcinoma tissue by using next-generation sequencing technology. Loman, N. Twenty years of bacterial genome sequencing. Venter, J.

Environmental genome shotgun sequencing of the Sargasso Sea. Science , 66—74 Mulcahy-O'Grady, H. The challenge and potential of metagenomics in the clinic. Hoffmann, B. A variegated squirrel bornavirus associated with fatal human encephalitis. Perlejewski, K. Next-generation sequencing NGS in the identification of encephalitis-causing viruses: unexpected detection of human herpesvirus 1 while searching for RNA pathogens.

Methods , 1—6 Duncan, C. Transl Med. Morfopoulou, S. Human coronavirus OC43 associated with fatal encephalitis. Naccache, S. Diagnosis of neuroinvasive astrovirus infection in an immunocompromised adult with encephalitis by unbiased next-generation sequencing.

Huang, W. Whole-genome sequence analysis reveals the enterovirus D68 isolates during the United States outbreak mainly belong to a novel clade. This provides information about what is driving the spread of the virus both locally and nationally.

This work can be made more precise if virus genomes are combined with information about where, how and when people travel locally and internationally.

Virus genome sequences can also identify unique genetic changes shared by all those infected in a single virus transmission chain. This can be used to distinguish whether two clusters of cases in the same area have arisen because one started infection in the other, or because there were two distinct and independent chains of transmission with separate, earlier origins. Virus genomes can therefore add to the information provided by patient contact tracing, which is important for tracking outbreaks in communities, hospitals and other care settings.

Many genetic changes that occur in the genome of the virus will have no significant effect on the course of infection or disease, or the impact of control measures. However, a few of the changes might be important. These need to be identified and tracked through time. In viruses such as influenza, we know that genetic changes can alter how the immune system recognises viruses, resistance to antiviral drugs, and the severity of disease. These discoveries have yet to be made for the new coronavirus.

Rapid, large-scale virus genome sequencing is a new stream of information that can contribute to the tracking of epidemics and the development of new methods of control. Their work will help shed light on how the virus evolves as it spreads and how well containment efforts are working. Share on Twitter.

Share on Facebook. Pin it on Pinterest. More social media options Share on LinkedIn. Share on Reddit. Share on Tumblr. Related Content. You might also like. Discover JHU jhu. All rights reserved.



0コメント

  • 1000 / 1000