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Methods for Optimizing Mechanistic and Predictive Models of Human Disease
Methods for Optimizing Mechanistic and Predictive Models of Human Disease
Methods for Optimizing Mechanistic and Predictive Models of Human Disease

상세정보

자료유형  
 학위논문 서양
최종처리일시  
20250211151949
ISBN  
9798382789910
DDC  
574
저자명  
Mester, Rachel Shoshana.
서명/저자  
Methods for Optimizing Mechanistic and Predictive Models of Human Disease
발행사항  
[Sl] : University of California, Los Angeles, 2024
발행사항  
Ann Arbor : ProQuest Dissertations & Theses, 2024
형태사항  
175 p
주기사항  
Source: Dissertations Abstracts International, Volume: 85-12, Section: A.
주기사항  
Advisor: Pasaniuc, Bogdan.
학위논문주기  
Thesis (Ph.D.)--University of California, Los Angeles, 2024.
초록/해제  
요약A major goal of the biomathematics discipline is to optimize mathematical models for biological processes. This optimization can take on various forms; finding the appropriate model that fits available data, allows for accurate inference, and is computationally feasible is no easy task and requires an understanding of both the biological processes at hand and the mathematics behind each potential model or algorithm. In this dissertation, I seek to understand how mathematical modeling choices affect our ability to understand human disease. I study infectious, cancerous, and polygenic disease from a variety of computational perspectives. First, I apply methods for differential sensitivity analysis in biological models for both cancerous and infectious disease spread. I compare prediction accuracy for existing first-order methods and propose a second-order method with enhanced flexibility both in terms of the model for which it is applied and the programming environment available. Second, I compare statistical approaches for uncovering genetics of complex disease in admixed populations, using likelihood ratio tests to understand how to incorporate local ancestry in genome wide association studies to achieve the highest power. Third, I utilize machine learning methods to reduce diagnostic delay for patients across the University of California Health system. I adapt a logistic regression model to find patients likely to have common variable immune deficiencies from one health system to five health systems. I also adapt this algorithm from the immunology realm to the cardiology realm to predict cardiac amyloidosis. Along the way, I use this context to study automated feature selection, longitudinal feature engineering, and observational bias in electronic health record data.
일반주제명  
Bioinformatics
일반주제명  
Applied mathematics
일반주제명  
Biology
일반주제명  
Information science
키워드  
Electronic health record data
키워드  
Biological processes
키워드  
Mathematical modeling
키워드  
Infectious disease
기타저자  
University of California, Los Angeles Biomathematics 0121
기본자료저록  
Dissertations Abstracts International. 85-12A.
전자적 위치 및 접속  
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MARC

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■040    ▼aMiAaPQ▼cMiAaPQ
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■1001  ▼aMester,  Rachel  Shoshana.
■24510▼aMethods  for  Optimizing  Mechanistic  and  Predictive  Models  of  Human  Disease
■260    ▼a[Sl]▼bUniversity  of  California,  Los  Angeles▼c2024
■260  1▼aAnn  Arbor▼bProQuest  Dissertations  &  Theses▼c2024
■300    ▼a175  p
■500    ▼aSource:  Dissertations  Abstracts  International,  Volume:  85-12,  Section:  A.
■500    ▼aAdvisor:  Pasaniuc,  Bogdan.
■5021  ▼aThesis  (Ph.D.)--University  of  California,  Los  Angeles,  2024.
■520    ▼aA  major  goal  of  the  biomathematics  discipline  is  to  optimize  mathematical  models  for  biological  processes.    This  optimization  can  take  on  various  forms;  finding  the  appropriate  model  that  fits  available  data,  allows  for  accurate  inference,  and  is  computationally  feasible  is  no  easy  task  and  requires  an  understanding  of  both  the  biological  processes  at  hand  and  the  mathematics  behind  each  potential  model  or  algorithm.    In  this  dissertation,  I  seek  to  understand  how  mathematical  modeling  choices  affect  our  ability  to  understand  human  disease.    I  study  infectious,  cancerous,  and  polygenic  disease  from  a  variety  of  computational  perspectives.  First,  I  apply  methods  for  differential  sensitivity  analysis  in  biological  models  for  both  cancerous  and  infectious  disease  spread.    I  compare  prediction  accuracy  for  existing  first-order  methods  and  propose  a  second-order  method  with  enhanced  flexibility  both  in  terms  of  the  model  for  which  it  is  applied  and  the  programming  environment  available.    Second,  I  compare  statistical  approaches  for  uncovering  genetics  of  complex  disease  in  admixed  populations,  using  likelihood  ratio  tests  to  understand  how  to  incorporate  local  ancestry  in  genome  wide  association  studies  to  achieve  the  highest  power.  Third,  I  utilize  machine  learning  methods  to  reduce  diagnostic  delay  for  patients  across  the  University  of  California  Health  system.    I  adapt  a  logistic  regression  model  to  find  patients  likely  to  have  common  variable  immune  deficiencies  from  one  health  system  to  five  health  systems.    I  also  adapt  this  algorithm  from  the  immunology  realm  to  the  cardiology  realm  to  predict  cardiac  amyloidosis.  Along  the  way,  I  use  this  context  to  study  automated  feature  selection,  longitudinal  feature  engineering,  and  observational  bias  in  electronic  health  record  data.
■590    ▼aSchool  code:  0031.
■650  4▼aBioinformatics
■650  4▼aApplied  mathematics
■650  4▼aBiology
■650  4▼aInformation  science
■653    ▼aElectronic  health  record  data
■653    ▼aBiological  processes
■653    ▼aMathematical  modeling
■653    ▼aInfectious  disease
■690    ▼a0715
■690    ▼a0364
■690    ▼a0306
■690    ▼a0723
■71020▼aUniversity  of  California,  Los  Angeles▼bBiomathematics  0121.
■7730  ▼tDissertations  Abstracts  International▼g85-12A.
■790    ▼a0031
■791    ▼aPh.D.
■792    ▼a2024
■793    ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17162234▼nKERIS▼z이  자료의  원문은  한국교육학술정보원에서  제공합니다.

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