Ali Burak Özkaya1, Caner Geyik2,3. 1. Department of Medical Biochemistry, Faculty of Medicine, İzmir University of Economics, İzmir, Turkey. 2. Department of Medical Biochemistry, Faculty of Medicine, İstinye University, İstanbul, Turkey. 3. ISUMKAM Molecular Cancer Research Center, İstinye University, Istanbul, Turkey.
Abstract
BACKGROUND: Reliability of preclinical research is of critical concern. Prior studies have demonstrated the low reproducibility of research results and recommend implementing higher standards to improve overall quality and robustness of research. One understudied aspect of this quality issue is the harmony between the research hypotheses and the experimental design in published work. METHODS AND FINDINGS: In this study we focused on highly cited cell culture studies and investigated whether commonly asserted cell culture claims such as viability, cytotoxicity, proliferation rate, cell death and apoptosis are backed with sufficient experimental evidence or not. We created an open access database containing 280 claims asserted by 103 different high-impact articles as well as the results of this study. Our findings revealed that only 64% of all claims were sufficiently supported by evidence and there were concerning misinterpretations such as considering the results of tetrazolium salt reduction assays as indicators of cell death or apoptosis. CONCLUSIONS: Our analysis revealed a discordance between experimental findings and the way they were presented and discussed in the manuscripts. To improve quality of pre-clinical research, we require clear nomenclature by which different cell culture claims are distinctively categorized; materials and methods sections to be written more meticulously; and cell culture methods to be selected and utilized more carefully. In this paper we recommend a nomenclature for selected cell culture claims as well as a methodology for collecting evidence to support those claims.
BACKGROUND: Reliability of preclinical research is of critical concern. Prior studies have demonstrated the low reproducibility of research results and recommend implementing higher standards to improve overall quality and robustness of research. One understudied aspect of this quality issue is the harmony between the research hypotheses and the experimental design in published work. METHODS AND FINDINGS: In this study we focused on highly cited cell culture studies and investigated whether commonly asserted cell culture claims such as viability, cytotoxicity, proliferation rate, cell death and apoptosis are backed with sufficient experimental evidence or not. We created an open access database containing 280 claims asserted by 103 different high-impact articles as well as the results of this study. Our findings revealed that only 64% of all claims were sufficiently supported by evidence and there were concerning misinterpretations such as considering the results of tetrazolium salt reduction assays as indicators of cell death or apoptosis. CONCLUSIONS: Our analysis revealed a discordance between experimental findings and the way they were presented and discussed in the manuscripts. To improve quality of pre-clinical research, we require clear nomenclature by which different cell culture claims are distinctively categorized; materials and methods sections to be written more meticulously; and cell culture methods to be selected and utilized more carefully. In this paper we recommend a nomenclature for selected cell culture claims as well as a methodology for collecting evidence to support those claims.
Authors: Ly P Vu; Brian F Pickering; Yuanming Cheng; Sara Zaccara; Diu Nguyen; Gerard Minuesa; Timothy Chou; Arthur Chow; Yogesh Saletore; Matthew MacKay; Jessica Schulman; Christopher Famulare; Minal Patel; Virginia M Klimek; Francine E Garrett-Bakelman; Ari Melnick; Martin Carroll; Christopher E Mason; Samie R Jaffrey; Michael G Kharas Journal: Nat Med Date: 2017-09-18 Impact factor: 53.440