Full metadata
Title
Discovering subclones and their driver genes in tumors sequenced at standard depths
Description
Understanding intratumor heterogeneity and their driver genes is critical to
designing personalized treatments and improving clinical outcomes of cancers. Such
investigations require accurate delineation of the subclonal composition of a tumor, which
to date can only be reliably inferred from deep-sequencing data (>300x depth). The
resulting algorithm from the work presented here, incorporates an adaptive error model
into statistical decomposition of mixed populations, which corrects the mean-variance
dependency of sequencing data at the subclonal level and enables accurate subclonal
discovery in tumors sequenced at standard depths (30-50x). Tested on extensive computer
simulations and real-world data, this new method, named model-based adaptive grouping
of subclones (MAGOS), consistently outperforms existing methods on minimum
sequencing depth, decomposition accuracy and computation efficiency. MAGOS supports
subclone analysis using single nucleotide variants and copy number variants from one or
more samples of an individual tumor. GUST algorithm, on the other hand is a novel method
in detecting the cancer type specific driver genes. Combination of MAGOS and GUST
results can provide insights into cancer progression. Applications of MAGOS and GUST
to whole-exome sequencing data of 33 different cancer types’ samples discovered a
significant association between subclonal diversity and their drivers and patient overall
survival.
designing personalized treatments and improving clinical outcomes of cancers. Such
investigations require accurate delineation of the subclonal composition of a tumor, which
to date can only be reliably inferred from deep-sequencing data (>300x depth). The
resulting algorithm from the work presented here, incorporates an adaptive error model
into statistical decomposition of mixed populations, which corrects the mean-variance
dependency of sequencing data at the subclonal level and enables accurate subclonal
discovery in tumors sequenced at standard depths (30-50x). Tested on extensive computer
simulations and real-world data, this new method, named model-based adaptive grouping
of subclones (MAGOS), consistently outperforms existing methods on minimum
sequencing depth, decomposition accuracy and computation efficiency. MAGOS supports
subclone analysis using single nucleotide variants and copy number variants from one or
more samples of an individual tumor. GUST algorithm, on the other hand is a novel method
in detecting the cancer type specific driver genes. Combination of MAGOS and GUST
results can provide insights into cancer progression. Applications of MAGOS and GUST
to whole-exome sequencing data of 33 different cancer types’ samples discovered a
significant association between subclonal diversity and their drivers and patient overall
survival.
Date Created
2019
Contributors
- Ahmadinejad, Navid (Author)
- Liu, Li (Thesis advisor)
- Maley, Carlo (Committee member)
- Dinu, Valentin (Committee member)
- Arizona State University (Publisher)
Topical Subject
Resource Type
Extent
xii, 130 pages : color illustrations
Language
eng
Copyright Statement
In Copyright
Primary Member of
Peer-reviewed
No
Open Access
No
Handle
https://hdl.handle.net/2286/R.I.55668
Statement of Responsibility
by Navid Ahmadinejad
Description Source
Viewed on May 7, 2021
Level of coding
full
Note
thesis
Partial requirement for: Ph.D., Arizona State University, 2019
bibliography
Includes bibliographical references
Field of study: Bioinformatics
System Created
- 2020-01-14 09:20:03
System Modified
- 2021-08-26 09:47:01
- 3 years 2 months ago
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