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Predicting favorable landing pads for targeted integrations in Chinese hamster ovary cell lines by learning stability characteristics from random transgene integrations

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StabilityAnalysis

To identify factors associated with stable or unstable transgene expression, genomic and transcriptomic profiles were observed around the transgene integration sites as reported by Cergentis using the TLA-Seq data.

Genome (WGS):

  1. Small variants - single nucleotide variations and small INDELs
  2. Structural variations - Large insertions, deletions, inversions, duplications and translocations
  3. Low and high variability regions

Transcriptome (RNA-Seq):

  1. Differential expression
  2. Low and high expression peaks

For investigating association of genomic rearrangements at integration level with expression stability, TLA-Seq data was analyzed at early as well as late passage for the producer cell lines.

Based on the key factors observed while comparing stable and unstable cell lines, genome wide landing pads were reported both for the regions to target and for those to avoid during targeted transgene integration.

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Predicting favorable landing pads for targeted integrations in Chinese hamster ovary cell lines by learning stability characteristics from random transgene integrations

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