Abstract
Genomic instability has profound effects on cellular phenotypes. Studies have shown that pluripotent cells with abnormal karyotypes may grow faster, differentiate less and become more resistance to apoptosis. Previously, we showed that microarray gene expression profiles can be utilized for the analysis of chromosomal aberrations by comparing gene expression levels between normal and aneuploid samples. Here we adopted this method for RNA-Seq data and present eSNP-Karyotyping for the detection of chromosomal aberrations, based on measuring the ratio of expression between the two alleles. We demonstrate its ability to detect chromosomal gains and losses in pluripotent cells and their derivatives, as well as meiotic recombination patterns. This method is advantageous since it does not require matched diploid samples for comparison, is less sensitive to global expression changes caused by the aberration and utilizes already available gene expression profiles to determine chromosomal aberrations.
Highlights
Genomic instability has profound effects on cellular phenotypes
We initially adopted this methodology for global gene expression analysis obtained from RNA-Seq data, and developed a new strategy to analyse genomic integrity based on the expression of transcripts with allele bias
We generated a table of the merged expression values and divided each gene expression level by the median expression levels across all samples, as previously described for microarray intensity values[6,10]
Summary
Genomic instability has profound effects on cellular phenotypes. Studies have shown that pluripotent cells with abnormal karyotypes may grow faster, differentiate less and become more resistance to apoptosis. H uman pluripotent stem cells (hPSC) acquire chromosomal abnormalities during their derivation and their propagation in culture[1] These aberrations might affect cellular behaviours such as the cell cycle, apoptosis resistance, tumorigenicity and differentiation capabilities due to changes in expression levels of various genes[1,2,3,4,5]. We presented a methodology, named e-Karyotyping, for studying genomic instability by analysis of global gene expression using microarray data sets[6,7,10] This method is based on comparison of gene expression levels along chromosomes by comparing the sample of interest and a matched diploid sample, to look for regional differences in gene expression. This method enables a reliable and fast analysis of genomic integrity, without the need for comparison to a matched diploid sample
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