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Investigation of Messenger RNA Modifications in Nanopore Sequencing Data by Machine Learning Methods
Investigation of Messenger RNA Modifications in Nanopore Sequencing Data by Machine Learni...
Investigation of Messenger RNA Modifications in Nanopore Sequencing Data by Machine Learning Methods

Detailed Information

자료유형  
 학위논문 서양
최종처리일시  
20250211151115
ISBN  
9798382781860
DDC  
574
저자명  
Huang, Sihao.
서명/저자  
Investigation of Messenger RNA Modifications in Nanopore Sequencing Data by Machine Learning Methods
발행사항  
[Sl] : The University of Chicago, 2024
발행사항  
Ann Arbor : ProQuest Dissertations & Theses, 2024
형태사항  
162 p
주기사항  
Source: Dissertations Abstracts International, Volume: 85-12, Section: B.
주기사항  
Advisor: Pan, Tao.
학위논문주기  
Thesis (Ph.D.)--The University of Chicago, 2024.
초록/해제  
요약To date, over 170 types of modifications have been identified in RNA, in which around 10 types are discovered in mRNA. RNA modifications play important roles in transcription, mRNA stability, decay, splicing, translation, regulate the expression of genes and affect metabolisms. Thus, it's important to understand the abundance and distribution of RNA modifications in transcriptome, to better understand how these modifications affect the metabolisms and how these modifications are regulated to execute proper functions. Next generation sequencing methods provide a group of strategies to map the transcriptome wide distributions of RNA modifications and has resulted in meaningful biological discoveries. However, only DNA molecules could be directly run by NGS methods and thus all RNA modifications are detected by indirect approaches, depending on mutations, indels, reverse transcription stops, or immunoprecipitation enrichment brought about by the modified sites. In the past decade, the development of Nanopore sequencing enables the direct sequencing of RNA molecules, as well as RNA modifications. In this dissertation, I developed machine learning based pipelines NanoPsu and NanoSPA for mRNA modification identification from nanopore direct RNA sequencing data. NanoPsu identifies pseudouridine modifications from human transcriptome and the correlation of interferon induced gene expression and pseudouridylation is revealed. NanoSPA enables simultaneous mapping of mRNA m6 A and pseudouridine in human transcriptome and reveals the anti-coordination of the two modifications. Both m6 A and pseudouridine are discovered to have positive effect on translation and the effect of pseudouridine is stronger than m6 A. Besides, I and others in the Pan Lab also attempted to develop a pipeline to predict pseudouridine based on single reads and revealed the stoichiometry of pseudouridine and the linkages between multiple modification sites. The study develops pipelines to facilitate the modification identification from nanopore direct RNA sequencing data and reveals the potential roles of the modifications in viral infection response and translation. The methods could be applied to other species and samples for more biological discoveries. The pipelines are designed for convenient usage of public users and could be easily expanded to more RNA modifications in the future.
일반주제명  
Molecular biology
일반주제명  
Bioinformatics
일반주제명  
Biochemistry
일반주제명  
Genetics
일반주제명  
Biophysics
키워드  
Machine learning
키워드  
Nanopore sequencing
키워드  
Pseudouridine
키워드  
RNA modification
키워드  
Transcriptomics
기타저자  
The University of Chicago Biochemistry and Molecular Biophysics
기본자료저록  
Dissertations Abstracts International. 85-12B.
전자적 위치 및 접속  
로그인 후 원문을 볼 수 있습니다.

MARC

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■1001  ▼aHuang,  Sihao.▼0(orcid)0000-0001-8575-8555
■24510▼aInvestigation  of  Messenger  RNA  Modifications  in  Nanopore  Sequencing  Data  by  Machine  Learning  Methods
■260    ▼a[Sl]▼bThe  University  of  Chicago▼c2024
■260  1▼aAnn  Arbor▼bProQuest  Dissertations  &  Theses▼c2024
■300    ▼a162  p
■500    ▼aSource:  Dissertations  Abstracts  International,  Volume:  85-12,  Section:  B.
■500    ▼aAdvisor:  Pan,  Tao.
■5021  ▼aThesis  (Ph.D.)--The  University  of  Chicago,  2024.
■520    ▼aTo  date,  over  170  types  of  modifications  have  been  identified  in  RNA,  in  which  around  10  types  are  discovered  in  mRNA.  RNA  modifications  play  important  roles  in  transcription,  mRNA  stability,  decay,  splicing,  translation,  regulate  the  expression  of  genes  and  affect  metabolisms.  Thus,  it's  important  to  understand  the  abundance  and  distribution  of  RNA  modifications  in  transcriptome,  to  better  understand  how  these  modifications  affect  the  metabolisms  and  how  these  modifications  are  regulated  to  execute  proper  functions.  Next  generation  sequencing  methods  provide  a  group  of  strategies  to  map  the  transcriptome  wide  distributions  of  RNA  modifications  and  has  resulted  in  meaningful  biological  discoveries.  However,  only  DNA  molecules  could  be  directly  run  by  NGS  methods  and  thus  all  RNA  modifications  are  detected  by  indirect  approaches,  depending  on  mutations,  indels,  reverse  transcription  stops,  or  immunoprecipitation  enrichment  brought  about  by  the  modified  sites.  In  the  past  decade,  the  development  of  Nanopore  sequencing  enables  the  direct  sequencing  of  RNA  molecules,  as  well  as  RNA  modifications.  In  this  dissertation,  I  developed  machine  learning  based  pipelines  NanoPsu  and  NanoSPA  for  mRNA  modification  identification  from  nanopore  direct  RNA  sequencing  data.  NanoPsu  identifies  pseudouridine  modifications  from  human  transcriptome  and  the  correlation  of  interferon  induced  gene  expression  and  pseudouridylation  is  revealed.  NanoSPA  enables  simultaneous  mapping  of  mRNA  m6  A  and  pseudouridine  in  human  transcriptome  and  reveals  the  anti-coordination  of  the  two  modifications.  Both  m6  A  and  pseudouridine  are  discovered  to  have  positive  effect  on  translation  and  the  effect  of  pseudouridine  is  stronger  than  m6  A.  Besides,  I  and  others  in  the  Pan  Lab  also  attempted  to  develop  a  pipeline  to  predict  pseudouridine  based  on  single  reads  and  revealed  the  stoichiometry  of  pseudouridine  and  the  linkages  between  multiple  modification  sites.  The  study  develops pipelines  to  facilitate  the  modification  identification  from  nanopore  direct  RNA  sequencing  data  and  reveals  the  potential  roles  of  the  modifications  in  viral  infection  response  and  translation.  The  methods  could  be  applied  to  other  species  and  samples  for  more  biological  discoveries.  The  pipelines  are  designed  for  convenient  usage  of  public  users  and  could  be  easily  expanded  to  more  RNA  modifications  in  the  future.
■590    ▼aSchool  code:  0330.
■650  4▼aMolecular  biology
■650  4▼aBioinformatics
■650  4▼aBiochemistry
■650  4▼aGenetics
■650  4▼aBiophysics
■653    ▼aMachine  learning
■653    ▼aNanopore  sequencing
■653    ▼aPseudouridine
■653    ▼aRNA  modification
■653    ▼aTranscriptomics
■690    ▼a0307
■690    ▼a0715
■690    ▼a0786
■690    ▼a0487
■690    ▼a0369
■71020▼aThe  University  of  Chicago▼bBiochemistry  and  Molecular  Biophysics.
■7730  ▼tDissertations  Abstracts  International▼g85-12B.
■790    ▼a0330
■791    ▼aPh.D.
■792    ▼a2024
■793    ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17160779▼nKERIS▼z이  자료의  원문은  한국교육학술정보원에서  제공합니다.

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