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Cell-Type Deconvolution of Liquid Bi...

McDeed, Arthur Patrick, IV,

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Cell-Type Deconvolution of Liquid Biopsy Samples Using Methylated cfDNA: Methods and Clinical Applications /

Record Type:	Electronic resources : Monograph/item
Title/Author:	Cell-Type Deconvolution of Liquid Biopsy Samples Using Methylated cfDNA: Methods and Clinical Applications // Arthur Patrick McDeed IV.
Author:	McDeed, Arthur Patrick, IV,
Description:	1 electronic resource (170 pages)
Notes:	Source: Dissertations Abstracts International, Volume: 86-12, Section: B.
Contained By:	Dissertations Abstracts International86-12B.
Subject:	Biostatistics. -
Online resource:	https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=31936631
ISBN:	9798315788263

Cell-Type Deconvolution of Liquid Biopsy Samples Using Methylated cfDNA: Methods and Clinical Applications /
McDeed, Arthur Patrick, IV,

Cell-Type Deconvolution of Liquid Biopsy Samples Using Methylated cfDNA: Methods and Clinical Applications /Arthur Patrick McDeed IV. - 1 electronic resource (170 pages)

Source: Dissertations Abstracts International, Volume: 86-12, Section: B.

Liquid biopsy applications are rapidly emerging as a minimally-invasive approach to collect system-wide biomarkers for genomic monitoring of physiologic and disease-related changes. Dying cells release fragmented strands of DNA into the circulation, referred to as cell-free DNA (cfDNA). Decoding the cellular origins of cfDNA over time utilizing cell-type specific methylation patterns can reveal altered cellular contributions reflective of dynamic changes indicative of disease state, tissue-specific damage, and treatment-related adverse events. Advancements in methylome-wide sequencing methodologies have led to the generation of vast amounts of cfDNA methylation data, yet computational methods to analyze these data are lagging behind. Here, we develop and validate an end-to-end pipeline to identify cell-type specific differentially methylated marker regions and then use the regions to inform cell-type deconvolution of liquid biopsy samples. To demonstrate the clinical utility, computational methods are then applied to serial liquid biopsy samples from patients enrolled in the DREAMseq Trial. Novel melanocyte-specific methylation marker regions are identified and then used to estimate the abundance of melanocyte-derived cfDNA. We show the change in melanocyte-derived cfDNA abundance over treatment time course can be used as an early indicator of response to treatment.The clinical applications of the methods developed here are far-ranging. This work offers a step towards realizing the potential of serial liquid biopsy sampling to complement and advance the standards of care in oncology and other fields.

English

ISBN: 9798315788263Subjects--Topical Terms:

1002712
Biostatistics.
Subjects--Index Terms:

Cell-free DNA

Cell-Type Deconvolution of Liquid Biopsy Samples Using Methylated cfDNA: Methods and Clinical Applications /
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520 $a Liquid biopsy applications are rapidly emerging as a minimally-invasive approach to collect system-wide biomarkers for genomic monitoring of physiologic and disease-related changes. Dying cells release fragmented strands of DNA into the circulation, referred to as cell-free DNA (cfDNA). Decoding the cellular origins of cfDNA over time utilizing cell-type specific methylation patterns can reveal altered cellular contributions reflective of dynamic changes indicative of disease state, tissue-specific damage, and treatment-related adverse events. Advancements in methylome-wide sequencing methodologies have led to the generation of vast amounts of cfDNA methylation data, yet computational methods to analyze these data are lagging behind. Here, we develop and validate an end-to-end pipeline to identify cell-type specific differentially methylated marker regions and then use the regions to inform cell-type deconvolution of liquid biopsy samples. To demonstrate the clinical utility, computational methods are then applied to serial liquid biopsy samples from patients enrolled in the DREAMseq Trial. Novel melanocyte-specific methylation marker regions are identified and then used to estimate the abundance of melanocyte-derived cfDNA. We show the change in melanocyte-derived cfDNA abundance over treatment time course can be used as an early indicator of response to treatment.The clinical applications of the methods developed here are far-ranging. This work offers a step towards realizing the potential of serial liquid biopsy sampling to complement and advance the standards of care in oncology and other fields.
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653 $a Cell-free DNA
653 $a Deconvolution
653 $a Liquid biopsy
653 $a Methylation
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720 1 $a Wellstein, Anton $e degree supervisor.
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