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Statistical Challenges in Sequencing Data: Addressing Uncertainty in Analysis
Statistical Challenges in Sequencing Data: Addressing Uncertainty in Analysis
Detailed Information
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20260202102950
- ISBN
- 9798315703273
- DDC
- 574
- 저자명
- Wu, Euphy Y.
- 서명/저자
- Statistical Challenges in Sequencing Data: Addressing Uncertainty in Analysis
- 발행사항
- [Sl] : The University of North Carolina at Chapel Hill, 2024
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2024
- 형태사항
- 142 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 86-11, Section: B.
- 주기사항
- Advisor: Love, Michael I.;Rashid, Naim U.
- 학위논문주기
- Thesis (Ph.D.)--The University of North Carolina at Chapel Hill, 2024.
- 초록/해제
- 요약The advancement of high-throughput sequencing technologies has revolutionized biological research. However, these technologies also introduce new statistical uncertainties. In this work, we present novel statistical methods that account for statistical uncertainties and best practice to mitigate bias in analyzing sequencing data.In project 1, we focus on detecting allelic imbalance on the isoform level, caused by non-coding variants in the regulatory regions. This analysis requires accounting for inferential uncertainty, caused by multi-mapping of RNA-sequencing reads. Our proposed method, SEESAW, uses Salmon and Swish to offer analysis at various levels of resolution, while accounting for inferential uncertainty. In project 2, we address the challenge of detecting cell composition changes using paired single-cell RNA-sequencing (scRNA-seq) data in cancer research. We proposed a novel approach scSTMseq, a topic modeling-based framework designed to infer cell clusters and estimate clustering uncertainty while integrating cell-level covariates, such as time. We coupled this framework with Multivariate analysis of variance for repeated measures to infer cell composition changes.In project 3, we explored the CRISPR inference/activation screens to study the regulatory roles of non-coding elements. Unlike standard scRNA-seq, scaling-based normalization introduces selection bias due to correlations between perturbation states and the sequencing depth, which complicates the case-control classification. We demonstrated this bias and proposed Poisson regression as a better alternative for normalization in the CRISPR-i/a studies.
- 일반주제명
- Biostatistics
- 일반주제명
- Genetics
- 일반주제명
- Applied mathematics
- 일반주제명
- Bioinformatics
- 키워드
- RNA sequencing
- 키워드
- Topic modeling
- 기타저자
- The University of North Carolina at Chapel Hill Biostatistics
- 기본자료저록
- Dissertations Abstracts International. 86-11B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■00520260202102950
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■007cr#unu||||||||
■020 ▼a9798315703273
■035 ▼a(MiAaPQ)AAI31765103
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a574
■1001 ▼aWu, Euphy Y.
■24510▼aStatistical Challenges in Sequencing Data: Addressing Uncertainty in Analysis
■260 ▼a[Sl]▼bThe University of North Carolina at Chapel Hill▼c2024
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2024
■300 ▼a142 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 86-11, Section: B.
■500 ▼aAdvisor: Love, Michael I.;Rashid, Naim U.
■5021 ▼aThesis (Ph.D.)--The University of North Carolina at Chapel Hill, 2024.
■520 ▼aThe advancement of high-throughput sequencing technologies has revolutionized biological research. However, these technologies also introduce new statistical uncertainties. In this work, we present novel statistical methods that account for statistical uncertainties and best practice to mitigate bias in analyzing sequencing data.In project 1, we focus on detecting allelic imbalance on the isoform level, caused by non-coding variants in the regulatory regions. This analysis requires accounting for inferential uncertainty, caused by multi-mapping of RNA-sequencing reads. Our proposed method, SEESAW, uses Salmon and Swish to offer analysis at various levels of resolution, while accounting for inferential uncertainty. In project 2, we address the challenge of detecting cell composition changes using paired single-cell RNA-sequencing (scRNA-seq) data in cancer research. We proposed a novel approach scSTMseq, a topic modeling-based framework designed to infer cell clusters and estimate clustering uncertainty while integrating cell-level covariates, such as time. We coupled this framework with Multivariate analysis of variance for repeated measures to infer cell composition changes.In project 3, we explored the CRISPR inference/activation screens to study the regulatory roles of non-coding elements. Unlike standard scRNA-seq, scaling-based normalization introduces selection bias due to correlations between perturbation states and the sequencing depth, which complicates the case-control classification. We demonstrated this bias and proposed Poisson regression as a better alternative for normalization in the CRISPR-i/a studies.
■590 ▼aSchool code: 0153.
■650 4▼aBiostatistics
■650 4▼aGenetics
■650 4▼aApplied mathematics
■650 4▼aBioinformatics
■653 ▼aRNA sequencing
■653 ▼aTopic modeling
■653 ▼aPoisson regression
■690 ▼a0308
■690 ▼a0369
■690 ▼a0715
■690 ▼a0364
■71020▼aThe University of North Carolina at Chapel Hill▼bBiostatistics.
■7730 ▼tDissertations Abstracts International▼g86-11B.
■790 ▼a0153
■791 ▼aPh.D.
■792 ▼a2024
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17356554▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
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