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Ensemble Methods for Latent Structure Detection From Heterogeneous Genomic and Phenotypic Data
Ensemble Methods for Latent Structure Detection From Heterogeneous Genomic and Phenotypic ...
Ensemble Methods for Latent Structure Detection From Heterogeneous Genomic and Phenotypic Data

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자료유형  
 학위논문 서양
최종처리일시  
20260202104758
ISBN  
9798265408518
DDC  
574
저자명  
Danning, Rebecca.
서명/저자  
Ensemble Methods for Latent Structure Detection From Heterogeneous Genomic and Phenotypic Data
발행사항  
[Sl] : Harvard University, 2025
발행사항  
Ann Arbor : ProQuest Dissertations & Theses, 2025
형태사항  
107 p
주기사항  
Source: Dissertations Abstracts International, Volume: 87-05, Section: B.
주기사항  
Advisor: Lin, Xihong.
학위논문주기  
Thesis (Ph.D.)--Harvard University, 2025.
초록/해제  
요약Disentangling the hidden patterns within genomic and phenotypic data can improve our understanding of complex conditions. Recent methodological developments in statistics and machine learning have improved our ability to detect latent patterns in a variety of application areas; however, these methods are often unsuitable for some of the data types common to health and biomedical data. Likewise, many latent structure methods require prespecification of the dimensions of the latent space, which is typically unknown. In this work, we introduce three ensemble statistical and machine learning methods designed to fill in these gaps.In Chapter 1, we introduce LACE-UP (LAtent Class analysis Ensembled with Umap and Pca), an ensemble machine learning method that outperforms gold-standard and oracle methods for clustering multidimensional binary data. When applied to dietary behavior data from the UK Biobank, LACE-UP uncovers interpretable dietary subtypes that are associated with lipid levels and cardiovascular risk. In Chapter 2, we introduce SEEK-VEC (Spectral Ensembling of topic models with Eigenscore for K-agnostic Vocabulary Embedding and Classification), a spectral ensemble topic modeling method for count data that yields prioritization scores and grouping scores that enable variable classification, pattern detection, and model diagnostics. We show through simulations that SEEK-VEC outperforms standard methods, particularly in weaker signal strength settings. We apply SEEK-VEC to single-cell gene expression data, food preference questionnaire data, and self-reported psychopathology symptom data, and show that the method uncovers meaningful insights across a broad range of contexts. In Chapter 3, we introduce SEEK-VFI (Spectral Ensembling of topic models with Eigenscore for K-agnostic Variable Feature Identification), an extension of SEEK-VEC that ranks genes with respect to their relevance to cell trajectory structure. We show that SEEK-VFI outperforms leading methods for differentiating between trajectory-relevant and uninformative genes, and we apply SEEK-VFI to several single-cell RNA expression datasets and demonstrate its ability to recover the true trajectory structure within the data.This suite of methods, designed for non-continuous data, provide a lens into the latent structure underlying phenotypic and genomic data. These methods do not require the prespecification of the dimensions of the latent space and are robust to noise. Taken together, the promise of these methods and the development of similar methods in the future is a refined understanding of complex phenotypes and their underlying mechanisms, which in turn will improve diagnoses, prognoses, and care.
일반주제명  
Biostatistics
일반주제명  
Genetics
키워드  
Clustering
키워드  
Dimension reduction
키워드  
Ensemble methods
키워드  
Latent variable analysis
키워드  
Topic modeling
키워드  
Trajectory analysis
기타저자  
Harvard University Biostatistics
기본자료저록  
Dissertations Abstracts International. 87-05B.
전자적 위치 및 접속  
로그인 후 원문을 볼 수 있습니다.

MARC

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■1001  ▼aDanning,  Rebecca.
■24510▼aEnsemble  Methods  for  Latent  Structure  Detection  From  Heterogeneous  Genomic  and  Phenotypic  Data
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■500    ▼aSource:  Dissertations  Abstracts  International,  Volume:  87-05,  Section:  B.
■500    ▼aAdvisor:  Lin,  Xihong.
■5021  ▼aThesis  (Ph.D.)--Harvard  University,  2025.
■520    ▼aDisentangling  the  hidden  patterns  within  genomic  and  phenotypic  data  can  improve  our  understanding  of  complex  conditions.  Recent  methodological  developments  in  statistics  and  machine  learning  have  improved  our  ability  to  detect  latent  patterns  in  a  variety  of  application  areas;  however,  these  methods  are  often  unsuitable  for  some  of  the  data  types  common  to  health  and  biomedical  data.  Likewise,  many  latent  structure  methods  require  prespecification  of  the  dimensions  of  the  latent  space,  which  is  typically  unknown.  In  this  work,  we  introduce  three  ensemble  statistical  and  machine  learning  methods  designed  to  fill  in  these  gaps.In  Chapter  1,  we  introduce  LACE-UP  (LAtent  Class  analysis  Ensembled  with  Umap  and  Pca),  an  ensemble  machine  learning  method  that  outperforms  gold-standard  and  oracle  methods  for  clustering  multidimensional  binary  data.  When  applied  to  dietary  behavior  data  from  the  UK  Biobank,  LACE-UP  uncovers  interpretable  dietary  subtypes  that  are  associated  with  lipid  levels  and  cardiovascular  risk.  In  Chapter  2,  we  introduce  SEEK-VEC  (Spectral  Ensembling  of  topic  models  with  Eigenscore  for  K-agnostic  Vocabulary  Embedding  and  Classification),  a  spectral  ensemble  topic  modeling  method  for  count  data  that  yields  prioritization  scores  and  grouping  scores  that  enable  variable  classification,  pattern  detection,  and  model  diagnostics.  We  show  through  simulations  that  SEEK-VEC  outperforms  standard  methods,  particularly  in  weaker  signal  strength  settings.  We  apply  SEEK-VEC  to  single-cell  gene  expression  data,  food  preference  questionnaire  data,  and  self-reported  psychopathology  symptom  data,  and  show  that  the  method  uncovers  meaningful  insights  across  a  broad  range  of  contexts.  In  Chapter  3,  we  introduce  SEEK-VFI  (Spectral  Ensembling  of  topic  models  with  Eigenscore  for  K-agnostic  Variable  Feature  Identification),  an  extension  of  SEEK-VEC  that  ranks  genes  with  respect  to  their  relevance  to  cell  trajectory  structure.  We  show  that  SEEK-VFI  outperforms  leading  methods  for  differentiating  between  trajectory-relevant  and  uninformative  genes,  and  we  apply  SEEK-VFI  to  several  single-cell  RNA  expression  datasets  and  demonstrate  its  ability  to  recover  the  true  trajectory  structure  within  the  data.This  suite  of  methods,  designed  for  non-continuous  data,  provide  a  lens  into  the  latent  structure  underlying  phenotypic  and  genomic  data.  These  methods  do  not  require  the  prespecification  of  the  dimensions  of  the  latent  space  and  are  robust  to  noise.  Taken  together,  the  promise  of  these  methods  and  the  development  of  similar  methods  in  the  future  is  a  refined  understanding  of  complex  phenotypes  and  their  underlying  mechanisms,  which  in  turn  will  improve  diagnoses,  prognoses,  and  care.
■590    ▼aSchool  code:  0084.
■650  4▼aBiostatistics
■650  4▼aGenetics
■653    ▼aClustering
■653    ▼aDimension  reduction
■653    ▼aEnsemble  methods
■653    ▼aLatent  variable  analysis
■653    ▼aTopic  modeling
■653    ▼aTrajectory  analysis
■690    ▼a0308
■690    ▼a0369
■71020▼aHarvard  University▼bBiostatistics.
■7730  ▼tDissertations  Abstracts  International▼g87-05B.
■790    ▼a0084
■791    ▼aPh.D.
■792    ▼a2025
■793    ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17358831▼nKERIS▼z이  자료의  원문은  한국교육학술정보원에서  제공합니다.

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