Dissertation/ Thesis

Large scale single cell methods and pan-cancer analysis

Bibliographic Details
Title: Large scale single cell methods and pan-cancer analysis
Authors: Fang, Xiunan, 方秀南
Contributors: Ho, JWK
Publisher Information: The University of Hong Kong (Pokfulam, Hong Kong)
Publication Year: 2024
Collection: University of Hong Kong: HKU Scholars Hub
Subject Terms: Nucleotide sequence - Data processing, Cancer - Data processing
Description: The widespread adoption of single cell omic technologies has enabled generation of large cell atlases that often consists of more than hundreds of thousands of cells. The large data size and heterogeneity pose significant computational and scientific challenges. With limited computational resources, new scalable algorithms and software are required to properly analyze these atlas-scale single cell data sets. In this thesis, we present a collection of new algorithms, bioinformatics tools, and applications related to large-scale analysis of single cell omic data. • A scalable clustering method called FlowGrid that can significantly reduce run time when analyzing very large single cell omic data. • A web-based immersive visualization tool called StarmapVis that enables effective exploration of single cell and spatial omic data. • A high-throughput and sensitive single-nucleus total RNA sequencing technique called HHseq is developed for the detection of total RNA from frozen clinical samples such as tumors. Using HHseq, we collected more than 730,000 single nuclei from 32 patients with various tumor types. An innovative analysis platform has been established to specifically encompass the entire process from upstream to downstream. • The pan-cancer analysis focuses on dissecting the transcriptional changes happened in malignant cells. The functions of key cell types and regulatory genes are analyzed. Specifically, pan-cancer malignant cell sub-cluster are detected, ciliated-like malignant groups show important functions in cancer proliferating and signaling. Furthermore, the investigation reveals mutual mutations in small nuclear RNAs (RNU4-1, RNU6-31P) among malignant cells, highlighting their potential splicing effects on cancer markers implicated in tumorigenesis mechanisms. Overall, the thesis highlights the importance of large-scale single-cell analysis in understanding complex biological systems such as cancer. The insights gained from this research can have important implications for developing suitable ...
Document Type: doctoral or postdoctoral thesis
Language: English
Relation: HKU Theses Online (HKUTO); 991044829506303414; https://hub.hku.hk/handle/10722/344190
Availability: https://hub.hku.hk/handle/10722/344190
Rights: The author retains all proprietary rights, (such as patent rights) and the right to use in future works. ; This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
Accession Number: edsbas.A2945F2C
Database: BASE
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  – Url: https://hub.hku.hk/handle/10722/344190#
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PubType: Dissertation/ Thesis
PubTypeId: dissertation
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IllustrationInfo
Items – Name: Title
  Label: Title
  Group: Ti
  Data: Large scale single cell methods and pan-cancer analysis
– Name: Author
  Label: Authors
  Group: Au
  Data: <searchLink fieldCode="AR" term="%22Fang%2C+Xiunan%22">Fang, Xiunan</searchLink><br /><searchLink fieldCode="AR" term="%22方秀南%22">方秀南</searchLink>
– Name: Author
  Label: Contributors
  Group: Au
  Data: Ho, JWK
– Name: Publisher
  Label: Publisher Information
  Group: PubInfo
  Data: The University of Hong Kong (Pokfulam, Hong Kong)
– Name: DatePubCY
  Label: Publication Year
  Group: Date
  Data: 2024
– Name: Subset
  Label: Collection
  Group: HoldingsInfo
  Data: University of Hong Kong: HKU Scholars Hub
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  Data: <searchLink fieldCode="DE" term="%22Nucleotide+sequence+-+Data+processing%22">Nucleotide sequence - Data processing</searchLink><br /><searchLink fieldCode="DE" term="%22Cancer+-+Data+processing%22">Cancer - Data processing</searchLink>
– Name: Abstract
  Label: Description
  Group: Ab
  Data: The widespread adoption of single cell omic technologies has enabled generation of large cell atlases that often consists of more than hundreds of thousands of cells. The large data size and heterogeneity pose significant computational and scientific challenges. With limited computational resources, new scalable algorithms and software are required to properly analyze these atlas-scale single cell data sets. In this thesis, we present a collection of new algorithms, bioinformatics tools, and applications related to large-scale analysis of single cell omic data. • A scalable clustering method called FlowGrid that can significantly reduce run time when analyzing very large single cell omic data. • A web-based immersive visualization tool called StarmapVis that enables effective exploration of single cell and spatial omic data. • A high-throughput and sensitive single-nucleus total RNA sequencing technique called HHseq is developed for the detection of total RNA from frozen clinical samples such as tumors. Using HHseq, we collected more than 730,000 single nuclei from 32 patients with various tumor types. An innovative analysis platform has been established to specifically encompass the entire process from upstream to downstream. • The pan-cancer analysis focuses on dissecting the transcriptional changes happened in malignant cells. The functions of key cell types and regulatory genes are analyzed. Specifically, pan-cancer malignant cell sub-cluster are detected, ciliated-like malignant groups show important functions in cancer proliferating and signaling. Furthermore, the investigation reveals mutual mutations in small nuclear RNAs (RNU4-1, RNU6-31P) among malignant cells, highlighting their potential splicing effects on cancer markers implicated in tumorigenesis mechanisms. Overall, the thesis highlights the importance of large-scale single-cell analysis in understanding complex biological systems such as cancer. The insights gained from this research can have important implications for developing suitable ...
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  Data: doctoral or postdoctoral thesis
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  Data: https://hub.hku.hk/handle/10722/344190
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  Data: The author retains all proprietary rights, (such as patent rights) and the right to use in future works. ; This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
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  Data: edsbas.A2945F2C
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  BibEntity:
    Languages:
      – Text: English
    Subjects:
      – SubjectFull: Nucleotide sequence - Data processing
        Type: general
      – SubjectFull: Cancer - Data processing
        Type: general
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      – TitleFull: Large scale single cell methods and pan-cancer analysis
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            NameFull: Fang, Xiunan
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            NameFull: 方秀南
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            NameFull: Ho, JWK
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          Dates:
            – D: 01
              M: 01
              Type: published
              Y: 2024
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