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Integrative Bioinformatics Analyses ...
~
The Chinese University of Hong Kong (Hong Kong).
Integrative Bioinformatics Analyses Using Next-Generation Sequencing : = Super-Enhancer Characterization in Skeletal Muscle Differentiation and Genomic and Methylomic Exploration in Plasma DNA.
紀錄類型:
書目-語言資料,手稿 : Monograph/item
正題名/作者:
Integrative Bioinformatics Analyses Using Next-Generation Sequencing :/
其他題名:
Super-Enhancer Characterization in Skeletal Muscle Differentiation and Genomic and Methylomic Exploration in Plasma DNA.
作者:
Peng, Xianlu.
面頁冊數:
1 online resource (178 pages)
附註:
Source: Dissertation Abstracts International, Volume: 78-05(E), Section: B.
Contained By:
Dissertation Abstracts International78-05B(E).
標題:
Bioinformatics. -
電子資源:
click for full text (PQDT)
ISBN:
9781369426205
Integrative Bioinformatics Analyses Using Next-Generation Sequencing : = Super-Enhancer Characterization in Skeletal Muscle Differentiation and Genomic and Methylomic Exploration in Plasma DNA.
Peng, Xianlu.
Integrative Bioinformatics Analyses Using Next-Generation Sequencing :
Super-Enhancer Characterization in Skeletal Muscle Differentiation and Genomic and Methylomic Exploration in Plasma DNA. - 1 online resource (178 pages)
Source: Dissertation Abstracts International, Volume: 78-05(E), Section: B.
Thesis (Ph.D.)--The Chinese University of Hong Kong (Hong Kong), 2016.
Includes bibliographical references
Next-generation sequencing (NGS), or high-throughput massive parallel sequencing has largely enabled the exploration of various biological and medical questions at single-base resolution and on a genome-wide scale. In this thesis, I mainly discussed the bioinformatics analysis of NGS data in 3 different context, namely skeletal muscle differentiation, plasma DNA of systemic lupus erythematosus (SLE) and plasma DNA of pregnancy. To gain insights into transcriptional and epigenetic regulatory mechanisms in myogenic differentiation, ChIPseq (chromatin immunoprecipitation with massively parallel DNA sequencing) data and RNAseq data were analyzed to identify and characterize super-enhancers (SEs). In SLE plasma DNA analysis, DNA-seq and bisulfite-seq were employed to unveil the genomic and methylomic aberrations. Lastly, an algorithm was developed to accurately quantify fetal DNA fraction based on DNA-seq of maternal plasma DNA at shallow depth, together with microarray-based genotyping.
Electronic reproduction.
Ann Arbor, Mich. :
ProQuest,
2018
Mode of access: World Wide Web
ISBN: 9781369426205Subjects--Topical Terms:
583857
Bioinformatics.
Index Terms--Genre/Form:
554714
Electronic books.
Integrative Bioinformatics Analyses Using Next-Generation Sequencing : = Super-Enhancer Characterization in Skeletal Muscle Differentiation and Genomic and Methylomic Exploration in Plasma DNA.
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Super-Enhancer Characterization in Skeletal Muscle Differentiation and Genomic and Methylomic Exploration in Plasma DNA.
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Source: Dissertation Abstracts International, Volume: 78-05(E), Section: B.
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Adviser: Nelson L. S. Tang.
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Thesis (Ph.D.)--The Chinese University of Hong Kong (Hong Kong), 2016.
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Includes bibliographical references
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Next-generation sequencing (NGS), or high-throughput massive parallel sequencing has largely enabled the exploration of various biological and medical questions at single-base resolution and on a genome-wide scale. In this thesis, I mainly discussed the bioinformatics analysis of NGS data in 3 different context, namely skeletal muscle differentiation, plasma DNA of systemic lupus erythematosus (SLE) and plasma DNA of pregnancy. To gain insights into transcriptional and epigenetic regulatory mechanisms in myogenic differentiation, ChIPseq (chromatin immunoprecipitation with massively parallel DNA sequencing) data and RNAseq data were analyzed to identify and characterize super-enhancers (SEs). In SLE plasma DNA analysis, DNA-seq and bisulfite-seq were employed to unveil the genomic and methylomic aberrations. Lastly, an algorithm was developed to accurately quantify fetal DNA fraction based on DNA-seq of maternal plasma DNA at shallow depth, together with microarray-based genotyping.
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SEs are clusters of closely located enhancers occupied by high-density master transcription factors (TFs), histone modifiers and transcription apparatus, and undergo active transcription per se. In the skeletal muscle, comprehensive study of SEs and SE-associated non-coding RNAs (seRNAs) is unavailable. To fill the gap, first of all, I identified SEs utilizing ChIP-seq datasets of H3K27ac, H3K4me1 and p300 from mouse C2C12 myoblasts and myotubes. Subsequently, by collecting and analyzing multiple TF ChIP-seq datasets, assembly of these TFs in SEs were revealed. Finally, the transcription extent of seRNAs was inspected and de novo transcript assembly was performed to screen for stable candidate seRNAs for experimental validation.
520
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SLE is a prototype autoimmune disease in which detailed biological characterization of circulating DNA is lacking. Through DNA-seq analysis of SLE plasma, aberration in the distribution of DNA molecules along the genome was demonstrated. Further, an obvious elevation in short proportion for the size profiles of plasma DNA molecules in active SLE cases was observed. Apart from this, hypo-methylation was also observed genome-wide unraveled by bisulfite sequencing.
520
$a
Fetal DNA fraction in circulating DNA of maternal plasma is a crucial parameter for noninvasive prenatal testing (NIPT) by massively parallel sequencing of maternal plasma DNA. Though multiple existing methods have been described for determining fetal DNA fraction, there is a vacancy for algorithms based on low-depth sequencing data. To this end, I codeveloped an algorithm, FetalQuant SD, which requires as low as 0.03 fold sequencing coverage of the human genome, as well as maternal genotype information, yet allows robust estimation of fetal DNA fraction for all pregnancies.
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In summary, this study has proved the applicability and feasibility of NGS data in modern research on genomics, epigenetics, and transcriptomics.
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click for full text (PQDT)
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