Evidence map›Paper›PMID 33095445›Full record

ArticleBiotechnology and bioengineering2021

High-resolution three-dimensional chromatin profiling of the Chinese hamster ovary cell genome.

Stephen Bevan, Stefan Schoenfelder, Robert J Young, Lin Zhang, Simon Andrews, Peter Fraser, Peter M O'Callaghan

Open access · hybridAbstract read
In one paragraph

Article in Biotechnology and bioengineering, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.3field-weighted citation impact, top 42% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 6 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 4 institutions in 2 countries.

Stephen BevanNuclear Dynamics Programme, The Babraham Institute, Babraham Research Campus, Cambridge, UK.
Stefan SchoenfelderNuclear Dynamics Programme, The Babraham Institute, Babraham Research Campus, Cambridge, UK.
Robert J YoungR&D Cell Engineering, Lonza Biologics, Little Chesterford, UK.
Lin ZhangCell Line Development, World Wide Pharmaceutical Sciences, BioTherapeutics Research and Development, Pfizer Inc., Andover, Massachusetts, USA.
Simon AndrewsBioinformatics Facility, The Babraham Institute, Cambridge, UK.
Peter FraserNuclear Dynamics Programme, The Babraham Institute, Babraham Research Campus, Cambridge, UK.
Peter M O'CallaghanR&D Cell Engineering, Lonza Biologics, Little Chesterford, UK.ORCID 0000-0003-4292-620X
Babraham Institute · GBCellCentric (United Kingdom) · GBFlorida State University · USPfizer (United States) · US

Funding

Biotechnology and Biological Sciences Research Council BB/M503241/1Medical Research Council MR/T016787/1
6 · The paper itself

Abstract

Chinese hamster ovary (CHO) cell lines are the pillars of a multibillion-dollar biopharmaceutical industry producing recombinant therapeutic proteins. The effects of local chromatin organization and epigenetic repression within these cell lines result in unpredictable and unstable transgene expression following random integration. Limited knowledge of the CHO genome and its higher order chromatin organization has thus far impeded functional genomics approaches required to tackle these issues. Here, we present an integrative three-dimensional (3D) map of genome organization within the CHOK1SV® 10E9 cell line in conjunction with an improved, less fragmented CHOK1SV 10E9 genome assembly. Using our high-resolution chromatin conformation datasets, we have assigned ≈90% of sequence to a chromosome-scale genome assembly. Our genome-wide 3D map identifies higher order chromatin structures such as topologically associated domains, incorporates our chromatin accessibility data to enhance the identification of active cis-regulatory elements, and importantly links these cis-regulatory elements to target promoters in a 3D promoter interactome. We demonstrate the power of our improved functional annotation by evaluating the 3D landscape of a transgene integration site and two phenotypically different cell lines. Our work opens up further novel genome engineering targets, has the potential to inform vital improvements for industrial biotherapeutic production, and represents a significant advancement for CHO cell line development.

Indexed as

Chromosome MappingGenomePromoter Regions, GeneticTransgenesAnimalsCHO CellsChromatinCricetulusRecombinant ProteinsChromatinRecombinant Proteins3D genome organizationChinese hamster ovary (CHO)genome assemblyHi-Cpromoter interactome

Identifiers

PMID33095445
PMCPMC7894165
OpenAlexW3093687414

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.