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Harnessing Genomic Surveillance to Characterize the Molecular Epidemiology and Uncover Antiviral Resistance Mechanisms of SARS-CoV-2
Harnessing Genomic Surveillance to Characterize the Molecular Epidemiology and Uncover Ant...
Harnessing Genomic Surveillance to Characterize the Molecular Epidemiology and Uncover Antiviral Resistance Mechanisms of SARS-CoV-2

상세정보

자료유형  
 학위논문 서양
최종처리일시  
20250211151415
ISBN  
9798382761275
DDC  
574
저자명  
Ling Hu, Ted.
서명/저자  
Harnessing Genomic Surveillance to Characterize the Molecular Epidemiology and Uncover Antiviral Resistance Mechanisms of SARS-CoV-2
발행사항  
[Sl] : Northwestern University, 2024
발행사항  
Ann Arbor : ProQuest Dissertations & Theses, 2024
형태사항  
302 p
주기사항  
Source: Dissertations Abstracts International, Volume: 85-11, Section: B.
주기사항  
Advisor: Hultquist, Judd F.
학위논문주기  
Thesis (Ph.D.)--Northwestern University, 2024.
초록/해제  
요약SARS-CoV-2, the causative agent of COVID-19, has had a devastating impact, resulting in over 7 million deaths worldwide. Like most viruses, SARS-CoV-2 has continued to evolve in order to adapt to selective pressures such as therapeutics and vaccines. These mutations have resulted in variants that demonstrate enhanced transmissibility, immune escape, or antiviral resistance. Genomic surveillance provides a framework in which to track the emergence of these mutations. We begin by outlining the genomic surveillance pipeline and address challenges and potential solutions associated with stage. Integrating these solutions, we conducted genomic surveillance to assess the association between SARS-CoV-2 clade and patient outcome over a two-year period. By the inclusion of population-level confounders, which includes sampling bias, we highlight the importance of integrating non-virological factors when examining patient risk. Furthermore, using the same approach, we examined the impact of remdesivir on SARS-CoV-2 diversity and evolution in vivo. Using sequences collected from patients before and after remdesivir administration, we identified several positions that showed preferential diversification after remdesivir treatment, several of which were associated with enhanced viral fitness. Taken together, our studies highlight the significant impact of SARS-CoV-2 mutations on disease dynamics as well as therapeutic interventions and emphasizes the necessity of using an integrative modeling approach to assess the impact of viral mutations. These findings underscore the ongoing evolution of the virus and the critical role of genomic surveillance in informing public health interventions and treatment strategies.
일반주제명  
Bioinformatics
일반주제명  
Biology
일반주제명  
Public health
일반주제명  
Epidemiology
일반주제명  
Genetics
키워드  
Antiviral resistance
키워드  
Genomic surveillance
키워드  
Remdesivir
키워드  
Immune escape
기타저자  
Northwestern University Driskill Graduate Training Program in Life Sciences
기본자료저록  
Dissertations Abstracts International. 85-11B.
전자적 위치 및 접속  
로그인 후 원문을 볼 수 있습니다.

MARC

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■24510▼aHarnessing  Genomic  Surveillance  to  Characterize  the  Molecular  Epidemiology  and  Uncover  Antiviral  Resistance  Mechanisms  of  SARS-CoV-2
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■260  1▼aAnn  Arbor▼bProQuest  Dissertations  &  Theses▼c2024
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■500    ▼aSource:  Dissertations  Abstracts  International,  Volume:  85-11,  Section:  B.
■500    ▼aAdvisor:  Hultquist,  Judd  F.
■5021  ▼aThesis  (Ph.D.)--Northwestern  University,  2024.
■520    ▼aSARS-CoV-2,  the  causative  agent  of  COVID-19,  has  had  a  devastating  impact,  resulting  in  over  7  million  deaths  worldwide.  Like  most  viruses,  SARS-CoV-2  has  continued  to  evolve  in  order  to  adapt  to  selective  pressures  such  as  therapeutics  and  vaccines.  These  mutations  have  resulted  in  variants  that  demonstrate  enhanced  transmissibility,  immune  escape,  or  antiviral  resistance.  Genomic  surveillance  provides  a  framework  in  which  to  track  the  emergence  of  these  mutations.  We  begin  by  outlining  the  genomic  surveillance  pipeline  and  address  challenges  and  potential  solutions  associated  with  stage.  Integrating  these  solutions,  we  conducted  genomic  surveillance  to  assess  the  association  between  SARS-CoV-2  clade  and  patient  outcome  over  a  two-year  period.  By  the  inclusion  of  population-level  confounders,  which  includes  sampling  bias,  we  highlight  the  importance  of  integrating  non-virological  factors  when  examining  patient  risk.  Furthermore,  using  the  same  approach,  we  examined  the  impact  of  remdesivir  on  SARS-CoV-2  diversity  and  evolution  in  vivo.  Using  sequences  collected  from  patients  before  and  after  remdesivir  administration,  we  identified  several  positions  that  showed  preferential  diversification  after  remdesivir  treatment,  several  of  which  were  associated  with  enhanced  viral  fitness.  Taken  together,  our  studies  highlight  the  significant  impact  of  SARS-CoV-2  mutations  on  disease  dynamics  as  well  as  therapeutic  interventions  and  emphasizes  the  necessity  of  using  an  integrative  modeling  approach  to  assess  the  impact  of  viral  mutations.  These  findings  underscore  the  ongoing  evolution  of  the  virus  and  the  critical  role  of  genomic  surveillance  in  informing  public  health  interventions  and  treatment  strategies.
■590    ▼aSchool  code:  0163.
■650  4▼aBioinformatics
■650  4▼aBiology
■650  4▼aPublic  health
■650  4▼aEpidemiology
■650  4▼aGenetics
■653    ▼aAntiviral  resistance
■653    ▼aGenomic  surveillance
■653    ▼aRemdesivir
■653    ▼aImmune  escape
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■71020▼aNorthwestern  University▼bDriskill  Graduate  Training  Program  in  Life  Sciences.
■7730  ▼tDissertations  Abstracts  International▼g85-11B.
■790    ▼a0163
■791    ▼aPh.D.
■792    ▼a2024
■793    ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17161577▼nKERIS▼z이  자료의  원문은  한국교육학술정보원에서  제공합니다.

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