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Advancing Biomedical Exploration: Leveraging Biomedical Knowledge Graphs With Computational Methods
Advancing Biomedical Exploration: Leveraging Biomedical Knowledge Graphs With Computationa...
Advancing Biomedical Exploration: Leveraging Biomedical Knowledge Graphs With Computational Methods

Detailed Information

자료유형  
 학위논문 서양
최종처리일시  
20250211153001
ISBN  
9798346383437
DDC  
600
저자명  
Ma, Chunyu.
서명/저자  
Advancing Biomedical Exploration: Leveraging Biomedical Knowledge Graphs With Computational Methods
발행사항  
[Sl] : The Pennsylvania State University, 2024
발행사항  
Ann Arbor : ProQuest Dissertations & Theses, 2024
형태사항  
196 p
주기사항  
Source: Dissertations Abstracts International, Volume: 86-05, Section: B.
주기사항  
Advisor: Koslicki, David.
학위논문주기  
Thesis (Ph.D.)--The Pennsylvania State University, 2024.
초록/해제  
요약Biomedical systems are highly complex, involving multiple disciplines such as biology, chemistry, clinical medicine, and environmental science. Understanding the inter- or intra- relationships of knowledge in these disciplines is beneficial for addressing a wide range of health-related issues (e.g., drug repurposing, pathogen detection). However, a single type of data or technique within a specific discipline often falls short in uncovering hidden connections across disciplines and fails to capture different views and holistically comprehend the relevant biomedical mechanisms. Although still in the early stage of practical applications, researchers have demonstrated the success of leveraging knowledge graph techniques to integrate unstructured knowledge into a structured semantic graph, allowing to explore more unknown relationships and properties based on the existing biomedical knowledge. In this dissertation, we aim to further advance the applications of knowledge graphs to explore biomedical issues by combining them with the novel machine learning (ML) method, a querying and reasoning system, as well as other computational algorithms.In Chapter 1, we first introduce the fundamental concepts about biomedical knowledge graphs (BKGs), existing BKG applications, a standardized data integration framework (i.e., Biolink model) and a large-scale standardized BKG (i.e., RTX-KG2) as the foundation of data standard and resource for most subsequent chapters. The chapter also discusses the existing problems and challenges of building and applying BKGs and summarizes the existing computational methods for BKG analysis. Some basic knowledge of metagenomics is also included to better understand Chapters 4 and 5.In Chapter 2, we present KGML-xDTD, a novel ML-based framework for enhancing the accuracy and biological interpretability of drug predictions by incorporating biomedical knowledge graphs. KGML-xDTD combines and utilizes the advantages of several machine learning models to capture different information (e.g., node attributes, graph structure) from biomedical knowledge graphs and innovatively uses the biological demonstration paths to guide the agent of reinforcement learning in finding biologically reasonable BKG paths as mechanism explanations. We also demonstrate its effectiveness via two case studies.In Chapter 3, we leverage biomedical knowledge graphs to answer biomedical questions and hypotheses and develop a querying and reasoning system called ARAX to achieve this goal. This system can efficiently and dynamically integrate more than 100 biomedical knowledge sources from around 40 knowledge providers (KPs) to explore biomedical systems and questions. It combines several computational algorithms including Fisher's exact test, Jaccard similarity, Normalized Google Distance, as well as the drug prediction model introduced in Chapter 2, to rank and select relevant knowledge as an ``answer'' for a given query.Chapters 4 and 5 together narrow down the application of knowledge graph techniques from broad biomedical questions to exploring biomedical issues in the field of metagenomics, the study of the genomic content of microbial communities. The work in chapter 4 constructs a metagenomics-focus biomedical knowledge graph -- MetagenomicKG. It integrates microbe-disease relevant knowledge including drugs, microbes (e.g., fungi, bacteria, viruses), genetic materials (e.g., genes, proteins), pathways, diseases. The work in Chapter 5 develops a metagenomics-based statistical tool that acts as a ``glue'' for connecting MetagenomicKG with specific metagenomic samples, which further enhances the dynamic analysis of knowledge graphs.In Chapter 6, we conclude the contribution of all my research work in this dissertation and also discuss the possibility of unifying knowledge graph techniques and large language models (LLM) to further facilitate BKG construction and exploration.
일반주제명  
Pathogens
일반주제명  
Hemophilia
일반주제명  
Funding
일반주제명  
Graph representations
일반주제명  
Taxonomy
일반주제명  
Huntingtons disease
일반주제명  
Bipolar disorder
일반주제명  
Genomes
일반주제명  
Coronaviruses
일반주제명  
Visualization
일반주제명  
Knowledge representation
일반주제명  
COVID-19
일반주제명  
Clinical psychology
일반주제명  
Genetics
일반주제명  
Medicine
기타저자  
The Pennsylvania State University.
기본자료저록  
Dissertations Abstracts International. 86-05B.
전자적 위치 및 접속  
로그인 후 원문을 볼 수 있습니다.

MARC

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■1001  ▼aMa,  Chunyu.
■24510▼aAdvancing  Biomedical  Exploration:  Leveraging  Biomedical  Knowledge  Graphs  With  Computational  Methods
■260    ▼a[Sl]▼bThe  Pennsylvania  State  University▼c2024
■260  1▼aAnn  Arbor▼bProQuest  Dissertations  &  Theses▼c2024
■300    ▼a196  p
■500    ▼aSource:  Dissertations  Abstracts  International,  Volume:  86-05,  Section:  B.
■500    ▼aAdvisor:  Koslicki,  David.
■5021  ▼aThesis  (Ph.D.)--The  Pennsylvania  State  University,  2024.
■520    ▼aBiomedical  systems  are  highly  complex,  involving  multiple  disciplines  such  as  biology,  chemistry,  clinical  medicine,  and  environmental  science.  Understanding  the  inter-  or  intra-  relationships  of  knowledge  in  these  disciplines  is  beneficial  for  addressing  a  wide  range  of  health-related  issues  (e.g.,  drug  repurposing,  pathogen  detection).  However,  a  single  type  of  data  or  technique  within  a  specific  discipline  often  falls  short  in  uncovering  hidden  connections  across  disciplines  and  fails  to  capture  different  views  and  holistically  comprehend  the  relevant  biomedical  mechanisms.  Although  still  in  the  early  stage  of  practical  applications,  researchers  have  demonstrated  the  success  of  leveraging  knowledge  graph  techniques  to  integrate  unstructured  knowledge  into  a  structured  semantic  graph,  allowing  to  explore  more  unknown  relationships  and  properties  based  on  the  existing  biomedical  knowledge.  In  this  dissertation,  we  aim  to  further  advance  the  applications  of  knowledge  graphs  to  explore  biomedical  issues  by  combining  them  with  the  novel  machine  learning  (ML)  method,  a  querying  and  reasoning  system,  as  well  as  other  computational  algorithms.In  Chapter  1,  we  first  introduce  the  fundamental  concepts  about  biomedical  knowledge  graphs  (BKGs),  existing  BKG  applications,  a  standardized  data  integration  framework  (i.e.,  Biolink  model)  and  a  large-scale  standardized  BKG  (i.e.,  RTX-KG2)  as  the  foundation  of  data  standard  and  resource  for  most  subsequent  chapters.  The  chapter  also  discusses  the  existing  problems  and  challenges  of  building  and  applying  BKGs  and  summarizes  the  existing  computational  methods  for  BKG  analysis.  Some  basic  knowledge  of  metagenomics  is  also  included  to  better  understand  Chapters  4  and  5.In  Chapter  2,  we  present  KGML-xDTD,  a  novel  ML-based  framework  for  enhancing  the  accuracy  and  biological  interpretability  of  drug  predictions  by  incorporating  biomedical  knowledge  graphs.  KGML-xDTD  combines  and  utilizes  the  advantages  of  several  machine  learning  models  to  capture  different  information  (e.g.,  node  attributes,  graph  structure)  from  biomedical  knowledge  graphs  and  innovatively  uses  the  biological  demonstration  paths  to  guide  the  agent  of  reinforcement  learning  in  finding  biologically  reasonable  BKG  paths  as  mechanism  explanations.  We  also  demonstrate  its  effectiveness  via  two  case  studies.In  Chapter  3,  we  leverage  biomedical  knowledge  graphs  to  answer  biomedical  questions  and  hypotheses  and  develop  a  querying  and  reasoning  system  called  ARAX  to  achieve  this  goal.  This  system  can  efficiently  and  dynamically  integrate  more  than  100  biomedical  knowledge  sources  from  around  40  knowledge  providers  (KPs)  to  explore  biomedical  systems  and  questions.  It  combines  several  computational  algorithms  including  Fisher's  exact  test,  Jaccard  similarity,  Normalized  Google  Distance,  as  well  as  the  drug  prediction  model  introduced  in  Chapter  2,  to  rank  and  select  relevant  knowledge  as  an  ``answer''  for  a  given  query.Chapters  4  and  5  together  narrow  down  the  application  of  knowledge  graph  techniques  from  broad  biomedical  questions  to  exploring  biomedical  issues  in  the  field  of  metagenomics,  the  study  of  the  genomic  content  of  microbial  communities.  The  work  in  chapter  4  constructs  a  metagenomics-focus  biomedical  knowledge  graph  --  MetagenomicKG.  It  integrates  microbe-disease  relevant  knowledge  including  drugs,  microbes  (e.g.,  fungi,  bacteria,  viruses),  genetic  materials  (e.g.,  genes,  proteins),  pathways,  diseases.  The  work  in  Chapter  5  develops  a  metagenomics-based  statistical  tool  that  acts  as  a  ``glue''  for  connecting  MetagenomicKG  with  specific  metagenomic  samples,  which  further  enhances  the  dynamic  analysis  of  knowledge  graphs.In  Chapter  6,  we  conclude  the  contribution  of  all  my  research  work  in  this  dissertation  and  also  discuss  the  possibility  of  unifying  knowledge  graph  techniques  and  large  language  models  (LLM)  to  further  facilitate  BKG  construction  and  exploration.
■590    ▼aSchool  code:  0176.
■650  4▼aPathogens
■650  4▼aHemophilia
■650  4▼aFunding
■650  4▼aGraph  representations
■650  4▼aTaxonomy
■650  4▼aHuntingtons  disease
■650  4▼aBipolar  disorder
■650  4▼aGenomes
■650  4▼aCoronaviruses
■650  4▼aVisualization
■650  4▼aKnowledge  representation
■650  4▼aCOVID-19
■650  4▼aClinical  psychology
■650  4▼aGenetics
■650  4▼aMedicine
■690    ▼a0622
■690    ▼a0369
■690    ▼a0564
■71020▼aThe  Pennsylvania  State  University.
■7730  ▼tDissertations  Abstracts  International▼g86-05B.
■790    ▼a0176
■791    ▼aPh.D.
■792    ▼a2024
■793    ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17164430▼nKERIS▼z이  자료의  원문은  한국교육학술정보원에서  제공합니다.

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