Journal article
Multi-omic measurements of heterogeneity in HeLa cells across laboratories.
- Liu Y Department of Pharmacology, Yale University School of Medicine, New Haven, CT, USA. yansheng.liu@yale.edu.
- Mi Y Heidelberg University, Faculty of Biosciences, Heidelberg, Germany.
- Mueller T Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland.
- Kreibich S Institute of Microbiology, ETH Zurich, Zurich, Switzerland.
- Williams EG Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland.
- Van Drogen A Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland.
- Borel C Department of Genetic Medicine and Development, University of Geneva Medical School, and University Hospitals of Geneva, Geneva, Switzerland.
- Frank M Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland.
- Germain PL IEO, European Institute of Oncology IRCCS, Milan, Italy.
- Bludau I Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland.
- Mehnert M Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland.
- Seifert M Institute for Medical Informatics and Biometry, Carl Gustav Carus Faculty of Medicine, Technische Universität Dresden, Dresden, Germany.
- Emmenlauer M Biozentrum, University of Basel, Basel, Switzerland.
- Sorg I Biozentrum, University of Basel, Basel, Switzerland.
- Bezrukov F Department of Genetic Medicine and Development, University of Geneva Medical School, and University Hospitals of Geneva, Geneva, Switzerland.
- Bena FS Service of Genetic Medicine, University Hospitals of Geneva, Geneva, Switzerland.
- Zhou H Department of Analytical Chemistry and CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
- Dehio C Biozentrum, University of Basel, Basel, Switzerland.
- Testa G IEO, European Institute of Oncology IRCCS, Milan, Italy.
- Saez-Rodriguez J Joint Research Center for Computational Biomedicine (JRC-COMBINE), Faculty of Medicine, RWTH Aachen University, Aachen, Germany.
- Antonarakis SE Department of Genetic Medicine and Development, University of Geneva Medical School, and University Hospitals of Geneva, Geneva, Switzerland.
- Hardt WD Institute of Microbiology, ETH Zurich, Zurich, Switzerland.
- Aebersold R Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland. aebersold@imsb.biol.ethz.ch.
- 2019-02-20
Published in:
- Nature biotechnology. - 2019
DNA Copy Number Variations
Genome, Human
Genomics
HeLa Cells
Humans
Proteome
Reproducibility of Results
Transcriptome
English
Reproducibility in research can be compromised by both biological and technical variation, but most of the focus is on removing the latter. Here we investigate the effects of biological variation in HeLa cell lines using a systems-wide approach. We determine the degree of molecular and phenotypic variability across 14 stock HeLa samples from 13 international laboratories. We cultured cells in uniform conditions and profiled genome-wide copy numbers, mRNAs, proteins and protein turnover rates in each cell line. We discovered substantial heterogeneity between HeLa variants, especially between lines of the CCL2 and Kyoto varieties, and observed progressive divergence within a specific cell line over 50 successive passages. Genomic variability has a complex, nonlinear effect on transcriptome, proteome and protein turnover profiles, and proteotype patterns explain the varying phenotypic response of different cell lines to Salmonella infection. These findings have implications for the interpretation and reproducibility of research results obtained from human cultured cells.
- Language
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- English
- Open access status
- closed
- Identifiers
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- DOI 10.1038/s41587-019-0037-y
- PMID 30778230
- Persistent URL
- https://folia.unifr.ch/global/documents/58058
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