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Mapping Variation in the Morphological Landscape of Human Cells With Optical Pooled Crispri Screening
Mapping Variation in the Morphological Landscape of Human Cells With Optical Pooled Crispr...
Mapping Variation in the Morphological Landscape of Human Cells With Optical Pooled Crispri Screening

상세정보

자료유형  
 학위논문 서양
최종처리일시  
20250211152116
ISBN  
9798384344797
DDC  
571.6
저자명  
De Los Reyes Labitigan, Ramon Lorenzo.
서명/저자  
Mapping Variation in the Morphological Landscape of Human Cells With Optical Pooled Crispri Screening
발행사항  
[Sl] : Stanford University, 2024
발행사항  
Ann Arbor : ProQuest Dissertations & Theses, 2024
형태사항  
105 p
주기사항  
Source: Dissertations Abstracts International, Volume: 86-03, Section: B.
주기사항  
Includes supplementary digital materials.
주기사항  
Advisor: Spudich, James.
학위논문주기  
Thesis (Ph.D.)--Stanford University, 2024.
초록/해제  
요약The contributions of individual genes to cell-scale morphology and cytoskeletal organization are challenging to define due to the wide intercellular variation of these complex phenotypes. We leveraged the controlled nature of image-based pooled screening to assess the impact of CRISPRi knockdown of 366 genes on cell and nuclear morphology in human U2OS osteosarcoma cells. Screen scale-up was facilitated by a new, efficient barcode readout method that successfully genotyped 85% of cells. Phenotype analysis using a deep learning algorithm, the β-variational autoencoder, produced a feature embedding space distinct from one derived from conventional morphological profiling, but detected similar gene hits while requiring minimal design decisions. We found 45 gene hits and visualized their effect by rationally constrained sampling of cells along the direction of phenotypic shift. By relating these phenotypic shifts to each other, we construct a quantitative and interpretable space of morphological variation in human cells.
일반주제명  
Cells
일반주제명  
CRISPR
일반주제명  
Bone cancer
일반주제명  
Microscopy
일반주제명  
Medical research
일반주제명  
Data processing
일반주제명  
Design
일반주제명  
Genotype & phenotype
일반주제명  
Genes
일반주제명  
Visualization
일반주제명  
Medical schools
일반주제명  
Bioengineering
일반주제명  
Bioinformatics
일반주제명  
Genetics
일반주제명  
Health education
일반주제명  
Medicine
일반주제명  
Oncology
일반주제명  
Education
기타저자  
Stanford University.
기본자료저록  
Dissertations Abstracts International. 86-03B.
전자적 위치 및 접속  
로그인 후 원문을 볼 수 있습니다.

MARC

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■1001  ▼aDe  Los  Reyes  Labitigan,  Ramon  Lorenzo.
■24510▼aMapping  Variation  in  the  Morphological  Landscape  of  Human  Cells  With  Optical  Pooled  Crispri  Screening
■260    ▼a[Sl]▼bStanford  University▼c2024
■260  1▼aAnn  Arbor▼bProQuest  Dissertations  &  Theses▼c2024
■300    ▼a105  p
■500    ▼aSource:  Dissertations  Abstracts  International,  Volume:  86-03,  Section:  B.
■500    ▼aIncludes  supplementary  digital  materials.
■500    ▼aAdvisor:  Spudich,  James.
■5021  ▼aThesis  (Ph.D.)--Stanford  University,  2024.
■520    ▼aThe  contributions  of  individual  genes  to  cell-scale  morphology  and  cytoskeletal  organization  are  challenging  to  define  due  to  the  wide  intercellular  variation  of  these  complex  phenotypes.  We  leveraged  the  controlled  nature  of  image-based  pooled  screening  to  assess  the  impact  of  CRISPRi  knockdown  of  366  genes  on  cell  and  nuclear  morphology  in  human  U2OS  osteosarcoma  cells.  Screen  scale-up  was  facilitated  by  a  new,  efficient  barcode  readout  method  that  successfully  genotyped  85%  of  cells.  Phenotype  analysis  using  a  deep  learning  algorithm,  the  β-variational  autoencoder,  produced  a  feature  embedding  space  distinct  from  one  derived  from  conventional  morphological  profiling,  but  detected  similar  gene  hits  while  requiring  minimal  design  decisions.  We  found  45  gene  hits  and  visualized  their  effect  by  rationally  constrained  sampling  of  cells  along  the  direction  of  phenotypic  shift.  By  relating  these  phenotypic  shifts  to  each  other,  we  construct  a  quantitative  and  interpretable  space  of  morphological  variation  in  human  cells.
■590    ▼aSchool  code:  0212.
■650  4▼aCells
■650  4▼aCRISPR
■650  4▼aBone  cancer
■650  4▼aMicroscopy
■650  4▼aMedical  research
■650  4▼aData  processing
■650  4▼aDesign
■650  4▼aGenotype  &  phenotype
■650  4▼aGenes
■650  4▼aVisualization
■650  4▼aMedical  schools
■650  4▼aBioengineering
■650  4▼aBioinformatics
■650  4▼aGenetics
■650  4▼aHealth  education
■650  4▼aMedicine
■650  4▼aOncology
■650  4▼aEducation
■690    ▼a0389
■690    ▼a0202
■690    ▼a0715
■690    ▼a0369
■690    ▼a0680
■690    ▼a0564
■690    ▼a0992
■690    ▼a0515
■71020▼aStanford  University.
■7730  ▼tDissertations  Abstracts  International▼g86-03B.
■790    ▼a0212
■791    ▼aPh.D.
■792    ▼a2024
■793    ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17162950▼nKERIS▼z이  자료의  원문은  한국교육학술정보원에서  제공합니다.

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