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High-throughput tools for functional genomics

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TitleInfo
Title
High-throughput tools for functional genomics
Name (type = personal)
NamePart (type = family)
Guay
NamePart (type = given)
Catherine L.
NamePart (type = date)
1979-
DisplayForm
Catherine L. Guay
Role
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author
Name (type = personal)
NamePart (type = family)
Nam
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Jongmin
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Jongmin Nam
Affiliation
Advisory Committee
Role
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chair
Name (type = corporate)
NamePart
Rutgers University
Role
RoleTerm (authority = RULIB)
degree grantor
Name (type = corporate)
NamePart
Camden Graduate School
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school
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Text
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theses
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DateCreated (qualifier = exact)
2018
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2018-05
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2018
Place
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xx
Language
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eng
Abstract (type = abstract)
Genetic information is stored in DNA sequences, referred to as the genome. Decoding the meaning of these sequences is a critical challenge in biology. The genome contains functional components that modulate information in the genome into cell type specific functions. Of these components, Cis-regulatory modules (CRMs) integrate transcription factor inputs to causally affect gene expression. The genomic locations and sequences of CRMs are useful for resolving interactions within gene regulatory networks, and are therefore useful to address fundamental questions pertaining to development, evolution, cancer, and genetic disease. My work addressed major methodological limitations in CRM analysis. Previously, there was no functional method to identify CRMs at genome-scale. Thus, I developed a Genome-scale Reporter Assay Method for CRMs, or GRAMc, that utilizes random 25bp DNA barcodes (N25s) as reporters to quantitatively and reproducibly identify CRMs across an entire genome. The method was applied in cultured human liver cells and in sea urchin embryos. Due to the limited delivery rate of reporter constructs into embryos, it is often advantageous to test GRAMc libraries containing long (>1kb) genomic inserts. Previously, there was no efficient way to characterize genome-scale reporter libraries containing long inserts. To overcome this limitation, I developed a bi-directional mate-pair library approach to characterize long insert containing libraries of genome-scale magnitude. Although genome-scale identification of CRMs is critical to increase cis-regulatory analysis, in embryos it is also necessary to characterize the spatial activity of CRMs. Available methods to identify the spatial activity of CRMs rely on image analysis. Due to the limited number of optically distinct reporter genes, image-based methods are limited to testing only a few CRMs at a time. To address this challenge, I developed a method for Multiplex and Mosaic Observation of Spatial information encoded In CRMs, or MMOSAIC, that increases throughput of spatial cis-regulatory analysis in embryos by several orders of magnitude over traditional imaging based approaches. Together, these tools for cis-regulatory analysis overcome several major limitations for the study of functional genomics
Subject (authority = RUETD)
Topic
Computational and Integrative Biology
Subject (authority = ETD-LCSH)
Topic
Genetic regulation
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Rutgers University Electronic Theses and Dissertations
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ETD_8939
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electronic resource
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application/pdf
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Note
Supplementary File: Figure 1
Extent
1 online resource (xiv, 130 p. : ill.)
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references
Note (type = statement of responsibility)
by Catherine L. Guay
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TitleInfo
Title
Camden Graduate School Electronic Theses and Dissertations
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rucore10005600001
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Identifier (type = doi)
doi:10.7282/T38G8Q21
Genre (authority = ExL-Esploro)
ETD doctoral
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Rights

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The author owns the copyright to this work.
RightsHolder (type = personal)
Name
FamilyName
Guay
GivenName
Catherine
MiddleName
L.
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2018-04-20 18:35:57
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Name
Catherine Guay
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Affiliation
Rutgers University. Camden Graduate School
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Author Agreement License
Detail
I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
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2018-05-31
DateTime (encoding = w3cdtf); (qualifier = exact); (point = end)
2018-11-30
Type
Embargo
Detail
Access to this PDF has been restricted at the author's request. It will be publicly available after November 30th, 2018.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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