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A resource for cell line authentication, annotation and quality control

Nature volume 520, pages 307311 (16 April 2015) | Download Citation

Abstract

Cell line misidentification, contamination and poor annotation affect scientific reproducibility. Here we outline simple measures to detect or avoid cross-contamination, present a framework for cell line annotation linked to short tandem repeat and single nucleotide polymorphism profiles, and provide a catalogue of synonymous cell lines. This resource will enable our community to eradicate the use of misidentified lines and generate credible cell-based data.

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References

  1. 1.

    American Type Culture Collection Standards Development Organization Workgroup ASN-0002. Cell line misidentification: the beginning of the end. Nature Rev. Cancer 10 441–448 (2010)

  2. 2.

    Editorial. Identity crisis. Nature 457, 935–936 (2009)

  3. 3.

    et al. Match criteria for human cell line authentication: where do we draw the line? Int. J. Cancer 132 2510–2519 (2013)

  4. 4.

    & STR DNA typing of human cell lines: detection of intra- and interspecies cross-contamination. Methods Mol. Biol. 946 27–38 (2013)

  5. 5.

    Editorial. Announcement: Reducing our irreproducibility. Nature 496, 398 (2013).

  6. 6.

    , & Fixing problems with cell lines. Science 346, 1452–1453 (2014)

  7. 7.

    Persistent use of “false” cell lines. Int. J. Cancer 122 1–4 (2008)

  8. 8.

    ICLAC. Naming a Cell Line (2014)

  9. 9.

    , , & A bioinformatics analysis of the cell line nomenclature. Bioinformatics 24 2760–2766 (2008)

  10. 10.

    & Biomedical language processing: what's beyond PubMed? Mol. Cell 21 589–594 (2006)

  11. 11.

    et al. COSMIC: mining complete cancer genomes in the Catalogue of Somatic Mutations in Cancer. Nucleic Acids Res. 39 D945–D950 (2011)

  12. 12.

    et al. The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity. Nature 483 603–607 (2012)

  13. 13.

    et al. Cell Line Data Base: structure and recent improvements towards molecular authentication of human cell lines. Nucleic Acids Res. 37 D925–D932 (2009)

  14. 14.

    , & Cell line cross-contamination: how aware are mammalian cell culturists of the problem and how to monitor it? In Vitro Cell. Dev. Biol. Anim. 40 211–215 (2004)

  15. 15.

    et al. Recommendation of short tandem repeat profiling for authenticating human cell lines, stem cells, and tissues. In Vitro Cell. Dev. Biol. Anim. 46 727–732 (2010)

  16. 16.

    et al. Cancer cell line identification by short tandem repeat profiling: power and limitations. FASEB J. 19 434–436 (2005)

  17. 17.

    , & Reliability of DNA-based sex tests. Nature Genet. 18 103 (1998)

  18. 18.

    et al. Cell line individualization by STR multiplex system in the cell bank found cross-contamination between ECV304 and EJ-1/T24. Tiss. Cult. Res. Commun. 18, 329–338 (1999)

  19. 19.

    et al. Short tandem repeat profiling provides an international reference standard for human cell lines. Proc. Natl Acad. Sci. USA 98 8012–8017 (2001)

  20. 20.

    et al. High-throughput SNP-based authentication of human cell lines. Int. J. Cancer 132 308–314 (2013)

  21. 21.

    , & Tissue identity testing of cancer by short tandem repeat polymorphism: pitfalls of interpretation in the presence of microsatellite instability. Hum. Pathol. 45 549–555 (2014)

  22. 22.

    et al. SNP array profiling of mouse cell lines identifies their strains of origin and reveals cross-contamination and widespread aneuploidy. BMC Genomics 15 847 (2014)

  23. 23.

    et al. Check your cultures! A list of cross-contaminated or misidentified cell lines. Int. J. Cancer 127 1–8 (2010)

  24. 24.

    et al. Species identification in cell culture: a two-pronged molecular approach. In Vitro Cell. Dev. Biol. Anim. 43 344–351 (2007)

  25. 25.

    & Changing medium and passaging cell lines. Nature Protocols 2 2276–2284 (2007)

  26. 26.

    et al. Intratumor heterogeneity in localized lung adenocarcinomas delineated by multiregion sequencing. Science. 346, 256–259 (2014)

  27. 27.

    Cell-line authentication: end the scandal of false cell lines. Nature 492 186 (2012)

  28. 28.

    Eradication of cross-contaminated cell lines: a call for action. Cell Biol. Toxicol. 23 367–372 (2007)

  29. 29.

    Wellcome Trust Sanger Institute. The Cell Lines Project (2015)

  30. 30.

    Centers for Disease Control and Prevention. International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM). (2011)

  31. 31.

    ICLAC. Database of Cross-contaminated or Misidentified Cell Lines (version 7 2, released 10 October 2014).

  32. 32.

    et al. High-throughput single nucleotide polymorphism genotyping using nanofluidic Dynamic Arrays. BMC Genomics 10 561 (2009)

  33. 33.

    et al. Species identification and confirmation of human and animal cell lines: a PCR-based method. Biotechniques 32 432–434,–436, 438–440 (2002)

  34. 34.

    , , & A simple method using beta-globin polymerase chain reaction for the species identification of animal cell lines–a progress report. In Vitro Cell. Dev. Biol. Anim. 39 468–475 (2003)

  35. 35.

    , , & Biological identifications through DNA barcodes. Proc. R. Soc. Lond. B 270 313–321 (2003)

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Acknowledgements

We thank S. Ghosh for bioinformatics support, E. Hall and Y. Reid (ATCC) for their intellectual input and expertise in genetic testing. M. Kline for supplying STR profiles. J. Settleman and D. Stokoe for discussions.

Author information

Author notes

    • Mamie Yu
    •  & Suresh K. Selvaraj

    These authors contributed equally to this work.

Affiliations

  1. Department of Discovery Oncology, Genentech Inc., South San Francisco, California 94080, USA

    • Mamie Yu
    • , Suresh K. Selvaraj
    • , May M. Y. Liang-Chu
    • , Genee Lee
    •  & Richard M. Neve
  2. Department of Bioinformatics and Computational Biology, Genentech Inc., South San Francisco, California 94080, USA

    • Sahar Aghajani
    • , Matthew Busse
    • , Jean Yuan
    • , Christiaan Klijn
    • , Richard Bourgon
    •  & Joshua S. Kaminker
  3. Department of Pathology, Genentech Inc., South San Francisco, California 94080, USA

    • Franklin Peale

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Contributions

This collection of authenticated cell line data will be made available through NCBI’s BioProject and BioSample databases, accessible through accession number PRJNA271020, for continued community development and refinement. R.M.N. conceived and supervised the study; M.Y., S.K.S., M.M.Y.L.-C. and G.L. were responsible for cell line banking, experimentation and data collection; S.A., M.B., J.Y., C.K., R.B. and J.S.K. performed data curation and wrote the code for SNP and STR analyses; R.M.N., M.Y., S.K.S., M.M.Y.L.-C., M.B. and F.P. performed manual curation of cell line nomenclature and associated data. All authors discussed the results and commented on the manuscript.

Competing interests

The majority of authors are employees of Genentech Inc. and/or hold stock in Roche.

Corresponding author

Correspondence to Richard M. Neve.

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DOI

https://doi.org/10.1038/nature14397

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