{"id":{"repo_id":"mit","oai_identifier":"oai:dspace.mit.edu:1721.1/143310"},"canonical_url":"https://search.dev.ndltd.org/etd/mit/oai:dspace.mit.edu:1721.1/143310","repository":{"repo_id":"mit","name":"MIT","base_url":"https://dspace.mit.edu/oai/request"},"display":{"title":"Non-Parametric Analyses of the Regulatory Roles of LINE-1 Retrotransposons during Motor Neuron Differentiation","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_html":"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_has_math":false,"creators":["Park, Hyunjin"],"institution":"Massachusetts Institute of Technology","degree_name":"Master","degree_level":null,"degree_discipline":null,"degree_department":"Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science","school":null,"contributors":[],"advisors":["Gifford, David K."],"committee_chairs":[],"committee_members":[],"year":2022,"date_issued":"2022-02","date_published":"2022-02","updated_at":"2026-07-22T22:21:16Z","subjects":[],"languages":[],"rights":["In Copyright - Educational Use Permitted","Copyright MIT"],"rights_urls":["http://rightsstatements.org/page/InC-EDU/1.0/"],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/1721.1/143310","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Gifford, David K."]},{"key":"dc:contributor.department","label":"Department","values":["Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science"]},{"key":"dc:creator","label":"Author","values":["Park, Hyunjin"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2022-06-15T13:11:33Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2022-06-15T13:11:33Z"]},{"key":"dc:date.issued","label":"Date","values":["2022-02"]},{"key":"dc:publisher","label":"Institution","values":["Massachusetts Institute of Technology"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Master","Master of Science in Electrical Engineering and Computer Science"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:rights","label":"Dc Rights","values":["In Copyright - Educational Use Permitted","Copyright MIT"]},{"key":"dc:rights.uri","label":"Rights URI","values":["http://rightsstatements.org/page/InC-EDU/1.0/"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://hdl.handle.net/1721.1/143310"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["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."]},{"key":"dc:description.degree","label":"Dc Description Degree","values":["S.M."]},{"key":"dc:title","label":"Title","values":["Non-Parametric Analyses of the Regulatory Roles of LINE-1 Retrotransposons during Motor Neuron Differentiation"]}]}],"canonical_facts":{"dc:contributor.advisor":["Gifford, David K."],"dc:contributor.department":["Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science"],"dc:creator":["Park, Hyunjin"],"dc:date.accessioned":["2022-06-15T13:11:33Z"],"dc:date.available":["2022-06-15T13:11:33Z"],"dc:date.issued":["2022-02"],"dc:description.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."],"dc:description.degree":["S.M."],"dc:identifier.uri":["https://hdl.handle.net/1721.1/143310"],"dc:publisher":["Massachusetts Institute of Technology"],"dc:rights":["In Copyright - Educational Use Permitted","Copyright MIT"],"dc:rights.uri":["http://rightsstatements.org/page/InC-EDU/1.0/"],"dc:title":["Non-Parametric Analyses of the Regulatory Roles of LINE-1 Retrotransposons during Motor Neuron Differentiation"],"dc:type":["Thesis"],"thesis:degree_name":["Master","Master of Science in Electrical Engineering and Computer Science"]},"updated_at":"2026-07-22T22:21:16Z"}