Genome-wide analysis of single nucleotide variants allows for robust and accurate assessment of clonal derivation in cell lines used to produce biologics.

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State: Public
Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_BE8E8002A0B6
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Genome-wide analysis of single nucleotide variants allows for robust and accurate assessment of clonal derivation in cell lines used to produce biologics.
Journal
Biotechnology and bioengineering
Author(s)
Kuhn A., Le Fourn V., Fisch I., Mermod N.
ISSN
1097-0290 (Electronic)
ISSN-L
0006-3592
Publication state
Published
Issued date
11/08/2020
Peer-reviewed
Oui
Language
english
Notes
Publication types: Journal Article
Publication Status: aheadofprint
Abstract
A clonally derived (or "monoclonal") cell line is a cell population derived from a single progenitor cell. Clonally derived cell lines are required for many biotechnological applications. For instance, recombinant mammalian cells used to produce therapeutic proteins are expected by regulatory authorities to be clonally derived. Assurance of clonal derivation (or "clonality") is usually obtained from the characterization of the procedure used for cell cloning, for instance by assessing the success rate of single-cell sorting but not by assessing the cell line itself. We have developed a method to assess clonal derivation directly from the genetic makeup of cells. The genomic test of clonality is based on whole-genome sequencing and statistical analysis of single nucleotide variants. This approach quantifies the clonal fractions present in nonclonal samples and it provides a measure of the probability that a cell line is derived from a single cell. Upon experimental validation of the test, we show that it is highly accurate and that it can robustly detect minor clonal fractions of as little as 1% of the cell population. Moreover, we find that it is applicable to various cell line development protocols. This approach can simplify development protocols and shorten timelines while ensuring clonal derivation with high confidence.
Keywords
biologic, cell line development, clonal derivation, genomics, high-throughput sequencing, monoclonality
Pubmed
Web of science
Open Access
Yes
Create date
22/01/2021 10:47
Last modification date
23/01/2021 8:10
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