Abstract
Factors that impact the reproducibility of experimental data are poorly understood. Five NIH-LINCS centers performed the same set of drug-response measurements and compared results. Technical and biological variables that impact precision and reproducibility and are also sensitive to biological context were the most problematic.
Original language | English (US) |
---|---|
Pages (from-to) | 35-48.e5 |
Journal | Cell Systems |
Volume | 9 |
Issue number | 1 |
DOIs | |
State | Published - Jul 24 2019 |
Keywords
- cancer drugs
- cell line
- dose response
- high[HYPHEN]throughput
- microscopy
- oncology
- pharmacology
- reproducibility
- screening
ASJC Scopus subject areas
- Pathology and Forensic Medicine
- Histology
- Cell Biology
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In: Cell Systems, Vol. 9, No. 1, 24.07.2019, p. 35-48.e5.
Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - A Multi-center Study on the Reproducibility of Drug-Response Assays in Mammalian Cell Lines
AU - LINCS Consortium
AU - Niepel, Mario
AU - Hafner, Marc
AU - Mills, Caitlin E.
AU - Subramanian, Kartik
AU - Williams, Elizabeth H.
AU - Chung, Mirra
AU - Gaudio, Benjamin
AU - Barrette, Anne Marie
AU - Stern, Alan D.
AU - Hu, Bin
AU - Korkola, James E.
AU - Shamu, Caroline E.
AU - Jayaraman, Gomathi
AU - Azeloglu, Evren U.
AU - Iyengar, Ravi
AU - Sobie, Eric A.
AU - Mills, Gordon B.
AU - Liby, Tiera
AU - Jaffe, Jacob D.
AU - Alimova, Maria
AU - Davison, Desiree
AU - Lu, Xiaodong
AU - Golub, Todd R.
AU - Subramanian, Aravind
AU - Shelley, Brandon
AU - Svendsen, Clive N.
AU - Ma'ayan, Avi
AU - Medvedovic, Mario
AU - Gray, Joe W.
AU - Birtwistle, Marc R.
AU - Heiser, Laura M.
AU - Sorger, Peter K.
N1 - Funding Information: We thank K. Ward for help with automation. This work was funded by grants U54HL127365 to P.K.S.; U54HG008098 to R.I., M.R.B., and E.A.S.; R01-GM104184 to M.R.B.; U54HL127624 to M.M. and A.M.; U54-HG008100 to J.W.G., L.M.H., and J.E.K.; U54-HG008097 to J.D.J.; U54NS091046 to C.N.S.; U54HL127366 to T.R.G. and A.D.S.; and T32GM062754 to A.M.B. Funding Information: We thank K. Ward for help with automation. This work was funded by grants U54HL127365 to P.K.S.; U54HG008098 to R.I. M.R.B. and E.A.S.; R01-GM104184 to M.R.B.; U54HL127624 to M.M. and A.M.; U54-HG008100 to J.W.G. L.M.H. and J.E.K.; U54-HG008097 to J.D.J.; U54NS091046 to C.N.S.; U54HL127366 to T.R.G. and A.D.S.; and T32GM062754 to A.M.B. M.N. M.H. C.E.M. K.S. E.H.W. J.E.K. J.W.G. M.R.B. L.M.H. and P.K.S. designed the study and led its execution. M.C. B.G. A.M.B. B.H. and A.D.S. participated in data collection and analysis. All authors edited the manuscript. Peter K. Sorger is a member of the SAB or Board Of Directors of Merrimack Pharmaceutical, Glencoe Software, Applied Biomath and RareCyte Inc and has equity in these companies. Sorger declares that none of these relationships are directly or indirectly related to the content of this manuscript. Caroline Shamu's spouse is a member of the SAB or Board of Directors of Merrimack Pharmaceutical, Glencoe Software, Applied Biomath and RareCyte Inc and she has equity in these companies. Shamu declares that none of these relationships are directly or indirectly related to the content of this manuscript. Joe W. Gray has licensed technologies to Abbott Diagnostics and Danaher and has ownership positions in PDX Pharmaceuticals and Convergent Genomics. Gray serves as an advisor to New Leaf Ventures and KromaTid. Gray currently receives research funding or other support from Thermo Fisher (formerly FEI), Zeiss, Danaher (Cepheid), Micron, PDX Pharmaceuticals, Susan G. Komen Foundation, the Prospect Creek Foundation, the NCI Cancer Systems Biology Program, the NCI Human Tumor Atlas Program and the NIH LINCS program. Mario Niepel is an employee of Ribon Therapeutics. Niepel declares that this relationship is not directly or indirectly related to the content of this manuscript. Marc Hafner is an employee of Genentech, Inc. Hafner declares that this relationship is not directly or indirectly related to the content of this manuscript. Gordon Mills is a consultant for or SAB member of AstraZeneca, Chrysalis, ImmunoMET, Ionis, Mills Institute for Personalized Care (MIPCC), Nuevolution, PDX Pharma, Signalchem Lifesciences, Symphogen, and Tarveda. Gordon Mills has financial relationships with Catena Pharmaceuticals, ImmunoMet, SignalChem, Spindletop Ventures, and Tarveda. Gordon Mills has licensed technology to Myriad Genetics and Nanostring. Gordon Mills currently receives research funding from AztraZeneca, Karus Therapeutics, Nanostring, Pfizer, Tesaro, as well as the following foundations: Adelson Medical Research Foundation, Breast Cancer Research Foundation, Komen Research Foundation, Ovarian Cancer Research Foundation, Prospect Creek Foundation. Todd Golub is a paid consultant to Foundation Medicine, Sherlock Biosciences, and GlaxoSmithKline. Funding Information: Peter K. Sorger is a member of the SAB or Board Of Directors of Merrimack Pharmaceutical, Glencoe Software, Applied Biomath and RareCyte Inc and has equity in these companies. Sorger declares that none of these relationships are directly or indirectly related to the content of this manuscript. Caroline Shamu’s spouse is a member of the SAB or Board of Directors of Merrimack Pharmaceutical, Glencoe Software, Applied Biomath and RareCyte Inc and she has equity in these companies. Shamu declares that none of these relationships are directly or indirectly related to the content of this manuscript. Joe W. Gray has licensed technologies to Abbott Diagnostics and Danaher and has ownership positions in PDX Pharmaceuticals and Convergent Genomics. Gray serves as an advisor to New Leaf Ventures and KromaTid. Gray currently receives research funding or other support from Thermo Fisher (formerly FEI), Zeiss, Danaher (Cepheid), Micron, PDX Pharmaceuticals , Susan G. Komen Foundation , the Prospect Creek Foundation , the NCI Cancer Systems Biology Program, the NCI Human Tumor Atlas Program and the NIH LINCS program. Mario Niepel is an employee of Ribon Therapeutics. Niepel declares that this relationship is not directly or indirectly related to the content of this manuscript. Marc Hafner is an employee of Genentech, Inc. Hafner declares that this relationship is not directly or indirectly related to the content of this manuscript. Gordon Mills is a consultant for or SAB member of AstraZeneca, Chrysalis, ImmunoMET, Ionis, Mills Institute for Personalized Care (MIPCC), Nuevolution, PDX Pharma, Signalchem Lifesciences, Symphogen, and Tarveda. Gordon Mills has financial relationships with Catena Pharmaceuticals, ImmunoMet, SignalChem, Spindletop Ventures, and Tarveda. Gordon Mills has licensed technology to Myriad Genetics and Nanostring. Gordon Mills currently receives research funding from AztraZeneca , Karus Therapeutics , Nanostring , Pfizer , Tesaro , as well as the following foundations: Adelson Medical Research Foundation , Breast Cancer Research Foundation , Komen Research Foundation , Ovarian Cancer Research Foundation , Prospect Creek Foundation . Todd Golub is a paid consultant to Foundation Medicine, Sherlock Biosciences, and GlaxoSmithKline. Publisher Copyright: © 2019 The Authors
PY - 2019/7/24
Y1 - 2019/7/24
N2 - Factors that impact the reproducibility of experimental data are poorly understood. Five NIH-LINCS centers performed the same set of drug-response measurements and compared results. Technical and biological variables that impact precision and reproducibility and are also sensitive to biological context were the most problematic.
AB - Factors that impact the reproducibility of experimental data are poorly understood. Five NIH-LINCS centers performed the same set of drug-response measurements and compared results. Technical and biological variables that impact precision and reproducibility and are also sensitive to biological context were the most problematic.
KW - cancer drugs
KW - cell line
KW - dose response
KW - high[HYPHEN]throughput
KW - microscopy
KW - oncology
KW - pharmacology
KW - reproducibility
KW - screening
UR - http://www.scopus.com/inward/record.url?scp=85069572276&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85069572276&partnerID=8YFLogxK
U2 - 10.1016/j.cels.2019.06.005
DO - 10.1016/j.cels.2019.06.005
M3 - Article
C2 - 31302153
AN - SCOPUS:85069572276
SN - 2405-4712
VL - 9
SP - 35-48.e5
JO - Cell Systems
JF - Cell Systems
IS - 1
ER -