Development of diagnostic methods using cell-free nucleic acids
Abstract/Contents
- Abstract
- Thanks to the rapid development of next generation sequencing (NGS) technology, sequencing of circulating cell-free DNA has been widely used for noninvasive prenatal diagnosis and showed great potential for cancer detection. My thesis work is centered on the application of NGS to analyze cell-free nucleic acids for diagnostic purposes, from the cell-free RNA in the plasma of pregnant women to the cell-free DNA in the cerebrospinal fluid (CSF) of brain cancer patients. In the first part of my thesis, we characterized the composition and dynamic changes of circulating cell-free RNA during pregnancy. Plasma encompasses a broad spectrum of RNA molecules, derived from both human and microorganisms. While the composition of the microbiome in plasma remained relatively stable, the human genes involved in hormonal regulation and immune response were differentially expressed during pregnancy. We also demonstrated that pathogenic infections during pregnancy could be globally monitored through cell-free RNA sequencing (RNA-seq). In the second part of my thesis, we did a proof-of-principle study for the detection of brain tumor mutations in CSF. We measured the concentration and size distribution of cell-free DNA in CSF. We quantified the tumor allele fractions in the CSF and plasma of ten brain tumor patients. Tumor mutations could be detected in the CSF of nine out of the ten patients. Tumor allele fractions were generally higher in CSF compared to plasma, except for patients with systemic metastasis. We longitudinally monitored the treatment response and relapse of two brain cancer patients by sequencing the DNA in CSF.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2016 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Pan, Wenying |
|---|---|
| Associated with | Stanford University, Department of Bioengineering. |
| Primary advisor | Quake, Stephen Ronald |
| Thesis advisor | Quake, Stephen Ronald |
| Thesis advisor | Altman, Russ |
| Thesis advisor | Blumenfeld, Yair |
| Thesis advisor | Stevenson, David |
| Advisor | Altman, Russ |
| Advisor | Blumenfeld, Yair |
| Advisor | Stevenson, David |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Wenying Pan. |
|---|---|
| Note | Submitted to the Department of Bioengineering. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2016. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2016 by Wenying Pan
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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