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oai:dspace.mit.edu:1721.1/1433102022-06-16T03:40:47Zcom_1721.1_7582com_1721.1_7581col_1721.1_131023

Gifford, David K. Park, Hyunjin Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science 2022-06-15T13:11:33Z 2022-06-15T13:11:33Z 2022-02 2022-03-04T20:59:54.917Z https://hdl.handle.net/1721.1/143310 Background: Repetitive elements make up a large portion of eukaryotic genomes, constituting two-thirds of human genome. Although their functional importance were recognized as early as 1950s, study of their functions is stagnated despite the advancements in next-generation sequencing due to difficulty in establishing the identities of specific elements involved in a biological process of interest, e.g. transcription factor (TF) binding, from functional data modalities such as ChIP-seq and ChIA-PET. Results: First, I present a non-parametric, k-mer based method that overcomes analysis ambiguities introduced by short read multimapping and the incompleteness of reference genomes in low-complexity regions. I use this method to elucidate inferential evidence for the cell type-specific binding of transcription factors to specific L1 subfamilies from ChIP-seq datasets. Second, I applied a method named Mates of Chimera (MoC) to identify L1-derived extrachromosomal circular DNAs (eccDNAs) from Circulome-seq datasets. I characterized differential eccDNA compositions in ESC and MN cell types and found differential enrichment of transcription factor binding motifs in cell type specific eccDNAs. Third, I present inferential evidence consistent with the hypothesis that some low-complexity regions may participate in chromatin interactions with cis-regulatory sequences in a cell-type specific manner analogous to enhancer-promoter interactions. Conclusion: The thesis elucidates a set of functional hypotheses concerning putative regulatory roles of repetitive elements, L1 elements in particular, that may be extrachromosomal. I base my hypotheses on a wide range of available data modalities including whole-genome sequencing, ChIP-seq, Circulome-seq, and ChIA-PET through non-parametric, k-mer based methods that do not rely on exact read alignment coordinates. S.M. Massachusetts Institute of Technology In Copyright - Educational Use Permitted Copyright MIT http://rightsstatements.org/page/InC-EDU/1.0/ Non-Parametric Analyses of the Regulatory Roles of LINE-1 Retrotransposons during Motor Neuron Differentiation Thesis application/pdf Master Master of Science in Electrical Engineering and Computer Science Publication unknown unknown <Publication xmlns="https://www.openaire.eu/cerif-profile/1.1/" id="4a7db00c-02ca-41d1-907a-1ec804ce38b9"> <Type xmlns="https://www.openaire.eu/cerif-profile/vocab/COAR_Publication_Types">http://purl.org/coar/resource_type/c_1843</Type> <Title>Non-Parametric Analyses of the Regulatory Roles of LINE-1 Retrotransposons during Motor Neuron Differentiation</Title> <PublishedIn> <Publication> </Publication> </PublishedIn> <PublicationDate>2022-02</PublicationDate> <Authors> <Author> <DisplayName>Park, Hyunjin</DisplayName> <Affiliation> <OrgUnit> </OrgUnit> </Affiliation> </Author> </Authors> <Editors> </Editors> <Publishers> <Publisher> <DisplayName>Massachusetts Institute of Technology</DisplayName> <OrgUnit /> </Publisher> </Publishers> <License>http://rightsstatements.org/page/InC-EDU/1.0/</License> <Abstract>Background: Repetitive elements make up a large portion of eukaryotic genomes, constituting two-thirds of human genome. Although their functional importance were recognized as early as 1950s, study of their functions is stagnated despite the advancements in next-generation sequencing due to difficulty in establishing the identities of specific elements involved in a biological process of interest, e.g. transcription factor (TF) binding, from functional data modalities such as ChIP-seq and ChIA-PET. Results: First, I present a non-parametric, k-mer based method that overcomes analysis ambiguities introduced by short read multimapping and the incompleteness of reference genomes in low-complexity regions. I use this method to elucidate inferential evidence for the cell type-specific binding of transcription factors to specific L1 subfamilies from ChIP-seq datasets. Second, I applied a method named Mates of Chimera (MoC) to identify L1-derived extrachromosomal circular DNAs (eccDNAs) from Circulome-seq datasets. I characterized differential eccDNA compositions in ESC and MN cell types and found differential enrichment of transcription factor binding motifs in cell type specific eccDNAs. Third, I present inferential evidence consistent with the hypothesis that some low-complexity regions may participate in chromatin interactions with cis-regulatory sequences in a cell-type specific manner analogous to enhancer-promoter interactions. Conclusion: The thesis elucidates a set of functional hypotheses concerning putative regulatory roles of repetitive elements, L1 elements in particular, that may be extrachromosomal. I base my hypotheses on a wide range of available data modalities including whole-genome sequencing, ChIP-seq, Circulome-seq, and ChIA-PET through non-parametric, k-mer based methods that do not rely on exact read alignment coordinates.</Abstract> <Access xmlns="http://purl.org/coar/access_right" > </Access> </Publication>