Joesch-Cohen Lena M, Glusman Gustavo
Institute for Systems Biology, Seattle, WA, USA.
Adv Genomics Genet. 2017;7:1-9. doi: 10.2147/AGG.S128824. Epub 2017 Feb 23.
Lymphoblastoid cell lines (LCLs) represent a convenient research tool for expanding the amount of biologic material available from an individual. LCLs are commonly used as reference materials, most notably from the Genome in a Bottle Consortium. However, the question remains how faithfully LCL-derived genome assemblies represent the germline genome of the donor individual as compared to the genome assemblies derived from peripheral blood mononuclear cells. We present an in-depth comparison of a large collection of LCL- and peripheral blood mononuclear cell-derived genomes in terms of distributions of coverage and copy number alterations. We found significant differences in the depth of coverage and copy number calls, which may be driven by differential replication timing. Importantly, these copy number changes preferentially affect regions closer to genes and with higher GC content. This suggests that genomic studies based on LCLs may display locus-specific biases, and that conclusions based on analysis of depth of coverage and copy number variation may require further scrutiny.
淋巴母细胞系（LCLs）是一种便捷的研究工具，可用于扩充个体可用生物材料的数量。LCLs通常用作参考材料，尤其是来自“瓶中基因组联盟”。然而，与源自外周血单核细胞的基因组组装相比，LCLs衍生的基因组组装在多大程度上忠实地代表供体个体的种系基因组仍是个问题。我们对大量LCLs和外周血单核细胞衍生的基因组在覆盖度分布和拷贝数变异方面进行了深入比较。我们发现覆盖深度和拷贝数调用存在显著差异，这可能是由不同的复制时间驱动的。重要的是，这些拷贝数变化优先影响更靠近基因且GC含量更高的区域。这表明基于LCLs的基因组研究可能存在位点特异性偏差，基于覆盖深度和拷贝数变异分析得出的结论可能需要进一步审视。
