Chialastri Alex, Flowers Kevin, Cogburn L Amarin, Fink Damien, Dashnau Jennifer L
Century Therapeutics, Technical Development and Manufacturing, Philadelphia, PA, 19104, USA.
BMC Genomics. 2025 Jul 14;26(1):666. doi: 10.1186/s12864-025-11799-0.
Cell line authentication and karyotype assessment are two critical quality control tests that should be performed when using cell lines for biologic research and are expected measurements for cell therapy development. The current paradigm requires two separate measurements to assess these attributes, therefore a single straightforward approach that could assess karyotype and authenticate cell lines is beneficial.
We have developed a new optical genome mapping based approach named OGM-ID which can authenticate cell lines utilizing the same data that has previously been demonstrated as an alternative for traditional karyotyping. OGM-ID utilizes genome wide large (> 500 bp) insertions and deletions to uniquely identify cell lines. OGM-ID can be used to determine interspecies and intraspecies contamination. Benchmarking of OGM-ID was performed using three different family lineages, where replicates were clearly identified, and the relative genetic distance between individuals could be further monitored utilizing the zygosity of variants. Additionally, the donor of wild type and edited iPSCs was correctly determined even after multiple clonal selection events. Current limitations of OGM-ID require control around the version of Bionano Solve used and similar depths of coverage between samples.
OGM-ID is a whole genome technique that produces results comparable to other cell line authentication techniques with the added benefit of obtaining a cell line’s karyotype simultaneously. OGM-ID’s ability to distinguish large insertions or deletions, which are common in genome editing, also gives it a unique ability to distinguish between multiple clonal iPSC-derived allogeneic cell product candidates derived from the same donor.
The online version contains supplementary material available at 10.1186/s12864-025-11799-0.
细胞系鉴定和核型评估是两项关键的质量控制测试，在将细胞系用于生物学研究时应进行这些测试，并且是细胞治疗开发的预期测量项目。当前的模式需要进行两项单独的测量来评估这些属性，因此，一种能够评估核型并鉴定细胞系的简单直接的方法将是有益的。
我们开发了一种基于光学基因组图谱的新方法，名为OGM-ID，它可以利用先前已被证明可替代传统核型分析的数据来鉴定细胞系。OGM-ID利用全基因组范围内的大（>500 bp）插入和缺失来唯一鉴定细胞系。OGM-ID可用于确定种间和种内污染。使用三个不同的家系谱系对OGM-ID进行了基准测试，在该测试中可以清楚地识别重复样本，并且可以利用变异的纯合性进一步监测个体之间的相对遗传距离。此外，即使经过多次克隆选择事件，野生型和编辑后的诱导多能干细胞的供体也能被正确确定。OGM-ID目前的局限性要求在使用的Bionano Solve版本以及样本之间类似的覆盖深度方面进行控制。
OGM-ID是一种全基因组技术，其产生的结果与其他细胞系鉴定技术相当，同时还具有能同时获得细胞系核型的额外优势。OGM-ID区分大插入或缺失（这在基因组编辑中很常见）的能力，也使其具有独特的能力来区分来自同一供体的多个克隆诱导多能干细胞衍生的同种异体细胞产品候选物。
在线版本包含可在10.1186/s12864-025-11799-0获取的补充材料。
