Dataset Information

Haplotype-resolved de novo assembly of the Vero cell line genome.

ABSTRACT: The Vero cell line is the most used continuous cell line for viral vaccine manufacturing with more than 40 years of accumulated experience in the vaccine industry. Additionally, the Vero cell line has shown a high affinity for infection by MERS-CoV, SARS-CoV, and recently SARS-CoV-2, emerging as an important discovery and screening tool to support the global research and development efforts in this COVID-19 pandemic. However, the lack of a reference genome for the Vero cell line has limited our understanding of host-virus interactions underlying such affinity of the Vero cell towards key emerging pathogens, and more importantly our ability to redesign high-yield vaccine production processes using Vero genome editing. In this paper, we present an annotated highly contiguous 2.9 Gb assembly of the Vero cell genome. In addition, several viral genome insertions, including Adeno-associated virus serotypes 3, 4, 7, and 8, have been identified, giving valuable insights into quality control considerations for cell-based vaccine production systems. Variant calling revealed that, in addition to interferon, chemokines, and caspases-related genes lost their functions. Surprisingly, the ACE2 gene, which was previously identified as the host cell entry receptor for SARS-CoV and SARS-CoV-2, also lost function in the Vero genome due to structural variations.

SUBMITTER: Sene MA

PROVIDER: S-EPMC8379168 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The HeLa cell line was established in 1951 from cervical cancer cells taken from a patient, Henrietta Lacks. This was the first successful attempt to immortalize human-derived cells in vitro. The robust growth and unrestricted distribution of HeLa cells resulted in its broad adoption--both intentionally and through widespread cross-contamination--and for the past 60 years it has served a role analogous to that of a model organism. The cumulative impact of the HeLa cell line on research is demonstrated by its occurrence in more than 74,000 PubMed abstracts (approximately 0.3%). The genomic architecture of HeLa remains largely unexplored beyond its karyotype, partly because like many cancers, its extensive aneuploidy renders such analyses challenging. We carried out haplotype-resolved whole-genome sequencing of the HeLa CCL-2 strain, examined point- and indel-mutation variations, mapped copy-number variations and loss of heterozygosity regions, and phased variants across full chromosome arms. We also investigated variation and copy-number profiles for HeLa S3 and eight additional strains. We find that HeLa is relatively stable in terms of point variation, with few new mutations accumulating after early passaging. Haplotype resolution facilitated reconstruction of an amplified, highly rearranged region of chromosome 8q24.21 at which integration of the human papilloma virus type 18 (HPV-18) genome occurred and that is likely to be the event that initiated tumorigenesis. We combined these maps with RNA-seq and ENCODE Project data sets to phase the HeLa epigenome. This revealed strong, haplotype-specific activation of the proto-oncogene MYC by the integrated HPV-18 genome approximately 500 kilobases upstream, and enabled global analyses of the relationship between gene dosage and expression. These data provide an extensively phased, high-quality reference genome for past and future experiments relying on HeLa, and demonstrate the value of haplotype resolution for characterizing cancer genomes and epigenomes.

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Haplotype-resolved de novo assembly of the Vero cell line genome.

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