Joint analysis of single‐cell and bulk tissue sequencing data to infer intratumor heterogeneity

Wei Sun, Chong Jin, Jonathan A. Gelfond, Ming‐Hui Chen and Joseph G. Ibrahim

Biometrics, 2020, vol. 76, issue 3, 983-994

Abstract: Many computational methods have been developed to discern intratumor heterogeneity (ITH) using DNA sequence data from bulk tumor samples. These methods share an assumption that two mutations arise from the same subclone if they have similar mutant allele‐frequencies (MAFs), and thus it is difficult or impossible to distinguish two subclones with similar MAFs. Single‐cell DNA sequencing (scDNA‐seq) data can be very informative for ITH inference. However, due to the difficulty of DNA amplification, scDNA‐seq data are often very noisy. A promising new study design is to collect both bulk and single‐cell DNA‐seq data and jointly analyze them to mitigate the limitations of each data type. To address the analytic challenges of this new study design, we propose a computational method named BaSiC (Bulk tumor and Single Cell), to discern ITH by jointly analyzing DNA‐seq data from bulk tumor and single cells. We demonstrate that BaSiC has comparable or better performance than the methods using either data type. We further evaluate BaSiC using bulk tumor and single‐cell DNA‐seq data from a breast cancer patient and several leukemia patients.

Date: 2020
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://doi.org/10.1111/biom.13198

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:bla:biomet:v:76:y:2020:i:3:p:983-994

Ordering information: This journal article can be ordered from
http://www.blackwell ... bs.asp?ref=0006-341X

Access Statistics for this article

More articles in Biometrics from The International Biometric Society
Bibliographic data for series maintained by Wiley Content Delivery ().