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The need for high-quality cell lines to tackle the COVID-19 pandemic

In a time where global collaboration is key to fight COVID-19, ambiguity about preclinical test results can lead to costly delays.

Researchers are working around the clock to deepen our understanding of COVID-19 and to develop drugs and vaccines to combat it. They rely on a high-quality toolbox of cell lines being readily available for research and production of antivirals and vaccines. High-quality biological materials act as shared building blocks for solid scientific work to combat a virus that affects all of our lives.

More than 9,000 articles were published on COVID-19 in the last month alone – some of which were published as preprints, which have not yet undergone peer review. Peer-reviewed journals have drastically accelerated their review process. Where the process from submission to publication pre-pandemic took ~119 days, for COVID-19-related work the process now takes ~60 days [1]. Cell quality requirements that editors would normally request from authors are likely to be relaxed in the rush to publication, increasing the risk for irreproducible science and complicating the path to applications. It is a difficult balance. Science Magazine writes that while it is a concern, “It’s still too soon to measure the quality of papers published during the pandemic rush based on citations or retractions […]” [2].


Let’s step back and place this concern in context:


Publishing fever and some statistics regarding the reproducibility crisis


In 2018, about 3,000,000 scholarly articles were published per year across more than 23,100 peer-reviewed journals [3]. However, only 2,700 articles were published in the top-tier Nature journals within the last 12 months. Authorship on this small fraction (<0.1%) of papers makes it more likely that your work will be seen, your next grant will be accepted, or your desired PI position will become a reality.

The pressure to publish in “high-impact” journals is tremendous. And caring for reproducibility may take a backseat in many laboratories. However, the reproducibility of published work is a rising concern for all of us:

  • High-impact journals such as Nature are reporting a rise in article retractions [4].

  • A survey from 2016 (commissioned by Nature) showed that more than 70% of researchers cannot reproduce other scientists’ experiments. More than half are unable to reproduce their own experiments [5].

  • Asked about research reproducibility, 52% of researchers who were surveyed acknowledged a “significant crisis” of reproducibility in science today [5].

To address irreproducible science, journal editors came together with the NIH to agree on a universal set of principles and guidelines for reporting preclinical research [6]. These guidelines have led to new journal requirements, including: 1) creation of reproducible workflows, and 2) consistent reporting on biological materials such as cell lines.

Therefore, new publication standards in Cell Press journals state you must add a "Key Resources Table" with information on all your reagents, including where you obtained your cell lines [7].

For Nature journals, you must not only describe your reagents, but also report if cell lines are known to be misidentified and if your samples were authenticated, including a description of the method used [8].


How incorrect cell lines waste time and funding dollars


Cell line identity errors are common in academia and the pharmaceutical industry. If you receive a cell line from a colleague, you have a one in six (16%) chance that it will be misidentified, whether this is due to mislabelling of a tube or contamination by another cell line [9]. Irreproducible experimental results obtained using incorrect cell lines can harm scientific progress. And dissemination of incorrect cell lines can harm a researcher’s reputation in the biomedical community, as work of their colleagues will be affected too.


There is a 16% chance your cell line is not what you think it is.

Even so, the reproducibility crisis is ongoing:

  • A recent survey (commissioned by ATCC) showed that 87% of scientists sourced cell lines from other laboratories, but only 29% of those scientists tested them to pick up identity problems [10].

  • It is thought that of the $56.4 billion spent on preclinical research each year in the United States, roughly $28.2 billion is wasted by irreproducible research, a shocking 50% of the entire budget [11].

  • Poor biological reagents and reference materials (including cell lines) make up about 36% of the wasted amount, and problems with laboratory protocols make up about 10%. Poor study design, data analysis, and reporting are responsible for the rest [11].

Documenting laboratory protocols like cell maintenance and cell manipulation can seem like a chore, and “small details” are often omitted from articles. STR profiling -- traditionally used for cell line authentication -- takes time and effort to organize because it is usually outsourced to a separate testing provider. However, all these “details” are critically important because they provide vital information that allows others to reproduce a method or experimental result.


We created FIND Cell to help solve the reproducibility crisis by making cell line tracking easy and intuitive for today’s laboratories.


FIND Cell tracks each cell line’s history and provenance. Cell lines are DNA-verified, allowing researchers to exchange cell lines with colleagues and compare experimental results, with confidence.


Genetic testing of cell lines


FIND Cell uses SNP analysis for cell line authentication. Usage of SNP analysis for cell identity confirmation is an up-and-coming alternative to STR profiling, and has several benefits. It’s just as effective, and can be more accurate when working with cell lines that show genetic instability [12]. Furthermore, the widespread availability of cheap and portable DNA sequencers like the MinION by Oxford Nanopore Technologies gives labs the option to use their own sequencing data, instead of outsourcing experimental work.


Using the FIND Cell platform, it is easy to upload DNA sequencing data and request authentication within minutes. Our SNP-based method compares uploaded data to a reference dataset to verify a cell line’s identity [13]. This means FIND Cell can quickly pick up the most common causes of misidentification, including accidental contamination and mislabelling.


FIND Cell helps users with strategizing which cell populations to test for repeat DNA verification over time, and which to monitor for testing at a later stage -- saving time and costs, and avoiding problems on the road to publication.


Biomedical progress is achieved by global collaboration -- irreproducible science halts this.

In the current, high-pressure situation in which we combat the COVID-19 pandemic, no time should be wasted. The provenance of cell lines should be known, and the risk that cell lines are mis-labelled or cross-contaminated should be low.


After nearly a century of cell culture and with a rising reproducibility crisis on our hands - it’s time to reinvent how we track and test our cell lines. Our role at FIND Genomics is to provide an innovative platform to support cutting-edge science.


To request a FIND Cell brochure email: info@findgen.bio





Written by: Amanda Capes-Davis PhD, Tyler Joseph, and Sophie Zaaijer PhD

Illustrations: Kate White



Key references:

  1. Horbach SJPM. Pandemic Publishing: Medical journals drastically speed up their publication process for Covid-19. bioRxiv. 2020. p. 2020.04.18.045963. doi:10.1101/2020.04.18.045963

  2. Editorial. Scientists are drowning in COVID-19 papers. Can new tools keep them afloat? In: Science | AAAS [Internet]. 13 May 2020 [cited 9 Jul 2020]. Available: https://www.sciencemag.org/news/2020/05/scientists-are-drowning-covid-19-papers-can-new-tools-keep-them-afloat

  3. S TM. International Association of Scientific, Technical and Medical Publishers Prins Willem Alexanderhof 5, The Hague, 2595BE, The Netherlands. Available: https://www.stm-assoc.org/2018_10_04_STM_Report_2018.pdf

  4. Editorial. Retraction challenges. Nature. 2014;514: 5. doi:10.1038/514005a

  5. Baker M. 1,500 scientists lift the lid on reproducibility. Nature. 2016;533: 452–454. doi:10.1038/533452a

  6. NIH. Principles and Guidelines for Reporting Preclinical Research. In: National Institutes of Health (NIH) [Internet]. 13 Aug 2015 [cited 9 Jul 2020]. Available: https://www.nih.gov/research-training/rigor-reproducibility/principles-guidelines-reporting-preclinical-research

  7. Editorial. STAR Methods: Cell Press. [cited 9 Jul 2020]. Available: https://www.cell.com/star-methods

  8. Editorial. Nature Reporting Life Sciences Research. Available: https://www.nature.com/documents/nr-reporting-life-sciences-research.pdf

  9. Drexler HG, Dirks WG, MacLeod RAF, Uphoff CC. False and mycoplasma-contaminated leukemia-lymphoma cell lines: time for a reappraisal. Int J Cancer. 2017;140: 1209–1214. doi:10.1002/ijc.30530

  10. ATCC. REPRODUCIBILITY REPORT. Available: https://www.atcc.org/~/media/PDFs/Marketing%20Material/Reproducibility/Reproducibility%20Report.ashx

  11. Freedman LP, Gibson MC, Ethier SP, Soule HR, Neve RM, Reid YA. Reproducibility: changing the policies and culture of cell line authentication. Nat Methods. 2015;12: 493–497. doi:10.1038/nmeth.3403

  12. Yu M, Selvaraj SK, Liang-Chu MMY, Aghajani S, Busse M, Yuan J, et al. A resource for cell line authentication, annotation and quality control. Nature. 2015;520: 307–311. doi:10.1038/nature14397

  13. Zaaijer S, Gordon A, Speyer D, Piccone R, Groen SC, Erlich Y. Rapid re-identification of human samples using portable DNA sequencing. Elife. 2017;6. doi:10.7554/eLife.27798


Key words:

#COVID-19

#celllines

#fastvaccine

#pandemic

#reproducibility



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