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Efficient Machine Learning Algorithms for Protein Structure Determination With Single-Particle Cryo-Electron Microscopy
Efficient Machine Learning Algorithms for Protein Structure Determination With Single-Part...
Efficient Machine Learning Algorithms for Protein Structure Determination With Single-Particle Cryo-Electron Microscopy

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자료유형  
 학위논문 서양
최종처리일시  
20260202104851
ISBN  
9798288816444
DDC  
572.86
저자명  
Levy, Axel Louis Romain.
서명/저자  
Efficient Machine Learning Algorithms for Protein Structure Determination With Single-Particle Cryo-Electron Microscopy
발행사항  
[Sl] : Stanford University, 2025
발행사항  
Ann Arbor : ProQuest Dissertations & Theses, 2025
형태사항  
181 p
주기사항  
Source: Dissertations Abstracts International, Volume: 87-02, Section: B.
주기사항  
Advisor: Dunne, Mike.
학위논문주기  
Thesis (Ph.D.)--Stanford University, 2025.
초록/해제  
요약Most biological processes responsible for life are carried out by molecular machines called proteins. Knowledge about their three-dimensional structures is key for understanding their functions and for designing new therapeutic compounds, but turning experimental measurements into structural information constitutes a remarkably challenging computational task. In particular, in single-particle cryo-electron microscopy (cryo-EM), an ensemble of three-dimensional (3D) density fields must be derived from a set of noisy and randomly oriented projections. In this thesis, we develop novel algorithms for reconstructing the 3D structures of proteins and other biomolecules from cryo-EM data. Our work focuses on the problem of jointly estimating structures and viewing angles using neural-based approaches. With cryoAI and cryoFIRE, we demonstrate the benefits of amortized inference in terms of computation time for homogeneous and heterogeneous reconstruction on experimental cryo-EM datasets. We also shed light on the limitations of amortized inference in highly noisy regimes and introduce, in cryoDRGN-AI, a two-stage orientation estimation strategy which we validate on challenging experimental datasets. Finally, this thesis describes an extension of cryoDRGN-AI, Hydra, for handling strong compositional heterogeneity.
일반주제명  
Ribonucleic acid--RNA
일반주제명  
Electrical engineering
키워드  
Molecular machines
키워드  
Compositional heterogeneity
키워드  
Single-particle cryo-electron microscopy
기타저자  
Stanford University.
기본자료저록  
Dissertations Abstracts International. 87-02B.
전자적 위치 및 접속  
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■035    ▼a(MiAaPQ)AAI32200964
■035    ▼a(MiAaPQ)Stanfordkq162cq2878
■040    ▼aMiAaPQ▼cMiAaPQ
■0820  ▼a572.86
■1001  ▼aLevy,  Axel  Louis  Romain.
■24510▼aEfficient  Machine  Learning  Algorithms  for  Protein  Structure  Determination  With  Single-Particle  Cryo-Electron  Microscopy
■260    ▼a[Sl]▼bStanford  University▼c2025
■260  1▼aAnn  Arbor▼bProQuest  Dissertations  &  Theses▼c2025
■300    ▼a181  p
■500    ▼aSource:  Dissertations  Abstracts  International,  Volume:  87-02,  Section:  B.
■500    ▼aAdvisor:  Dunne,  Mike.
■5021  ▼aThesis  (Ph.D.)--Stanford  University,  2025.
■520    ▼aMost  biological  processes  responsible  for  life  are  carried  out  by  molecular  machines  called  proteins.  Knowledge  about  their  three-dimensional  structures  is  key  for  understanding  their  functions  and  for  designing  new  therapeutic  compounds,  but  turning  experimental  measurements  into  structural  information  constitutes  a  remarkably  challenging  computational  task.  In  particular,  in  single-particle  cryo-electron  microscopy  (cryo-EM),  an  ensemble  of  three-dimensional  (3D)  density  fields  must  be  derived  from  a  set  of  noisy  and  randomly  oriented  projections.  In  this  thesis,  we  develop  novel  algorithms  for  reconstructing  the  3D  structures  of  proteins  and  other  biomolecules  from  cryo-EM  data.  Our  work  focuses  on  the  problem  of  jointly  estimating  structures  and  viewing  angles  using  neural-based  approaches.  With  cryoAI  and  cryoFIRE,  we  demonstrate  the  benefits  of  amortized  inference  in  terms  of  computation  time  for  homogeneous  and  heterogeneous  reconstruction  on  experimental  cryo-EM  datasets.  We  also  shed  light  on  the  limitations  of  amortized  inference  in  highly  noisy  regimes  and  introduce,  in  cryoDRGN-AI,  a  two-stage  orientation  estimation  strategy  which  we  validate  on  challenging  experimental  datasets.  Finally,  this  thesis  describes  an  extension  of  cryoDRGN-AI,  Hydra,  for  handling  strong  compositional  heterogeneity.
■590    ▼aSchool  code:  0212.
■650  4▼aRibonucleic  acid--RNA
■650  4▼aElectrical  engineering
■653    ▼aMolecular  machines
■653    ▼aCompositional  heterogeneity
■653    ▼aSingle-particle  cryo-electron  microscopy
■690    ▼a0544
■690    ▼a0800
■71020▼aStanford  University.
■7730  ▼tDissertations  Abstracts  International▼g87-02B.
■790    ▼a0212
■791    ▼aPh.D.
■792    ▼a2025
■793    ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17359221▼nKERIS▼z이  자료의  원문은  한국교육학술정보원에서  제공합니다.

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