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JNCI Journal of the National Cancer Institute 2003 95(1):14-18; doi:10.1093/jnci/95.1.14
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Journal of the National Cancer Institute, Vol. 95, No. 1, 14-18, January 1, 2003
© 2003 Oxford University Press


COMMENTARY

Pitfalls in the Use of DNA Microarray Data for Diagnostic and Prognostic Classification

Richard Simon, Michael D. Radmacher, Kevin Dobbin, Lisa M. McShane

Affiliations of authors:R. Simon, K. Dobbin, L. M. McShane, Biometric Research Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD; M. D. Radmacher, Departments of Biology and Mathematics, Kenyon College, Gambier, OH.

Correspondence to:Richard Simon, D.Sc., National Cancer Institute, 9000 Rockville Pike, MSC 7434, Bethesda, MD 20892-7434 (e-mail: rsimon@nih.gov).

The first 150 words of the full text of this article appear below.

DNA microarrays have made it possible to estimate the level of expression of thousands of genes for a sample of cells. Although biomedical investigators have been quick to adopt this powerful new research tool, accurate analysis and interpretation of the data have provided unique challenges. Indeed, many investigators are not experienced in the analytical steps needed to convert tens of thousands of noisy data points into reliable and interpretable biologic information. Although some investigators recognize the importance of collaborating with experienced biostatisticians to analyze microarray data, the number and availability of experienced biostatisticians is inadequate. Consequently, investigators are using available software to analyze their data, many seemingly without knowledge of potential pitfalls. Because of serious problems associated with the analysis and reporting of some DNA microarray studies, there is great interest in guidance on valid and effective methods for analysis of DNA microarray data.

The design and analysis strategy for . . . [Full Text of this Article]

EXPERIMENTAL OBJECTIVES DRIVE DESIGN AND ANALYSIS

LIMITATIONS OF CLUSTER ANALYSIS FOR CLASS PREDICTION

CLASS PREDICTION USING SUPERVISED METHODS

CROSS-VALIDATION OF PREDICTION ACCURACY

VALIDATION ON INDEPENDENT DATA

REPORTING THE ERROR RATE

CLAIMS FOR NEW CLASS PREDICTION METHODS

CONCLUSION


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Arterioscler. Thromb. Vasc. Bio.Home page
A.P.J.J. Bijnens, E. Lutgens, T. Ayoubi, J. Kuiper, A.J. Horrevoets, and M.J.A.P. Daemen
Genome-Wide Expression Studies of Atherosclerosis: Critical Issues in Methodology, Analysis, Interpretation of Transcriptomics Data
Arterioscler Thromb Vasc Biol, June 1, 2006; 26(6): 1226 - 1235.
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JCOHome page
J. A. Foekens, D. Atkins, Y. Zhang, F. C.G.J. Sweep, N. Harbeck, A. Paradiso, T. Cufer, A. M. Sieuwerts, D. Talantov, P. N. Span, et al.
Multicenter Validation of a Gene Expression-Based Prognostic Signature in Lymph Node-Negative Primary Breast Cancer
J. Clin. Oncol., April 10, 2006; 24(11): 1665 - 1671.
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JNCI J Natl Cancer InstHome page
V. Winnepenninckx, V. Lazar, S. Michiels, P. Dessen, M. Stas, S. R. Alonso, M.-F. Avril, P. L. Ortiz Romero, T. Robert, O. Balacescu, et al.
Gene expression profiling of primary cutaneous melanoma and clinical outcome.
J Natl Cancer Inst, April 5, 2006; 98(7): 472 - 482.
[Abstract] [Full Text] [PDF]


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BiostatisticsHome page
M. R. Segal
Microarray gene expression data with linked survival phenotypes: diffuse large-B-cell lymphoma revisited
Biostat., April 1, 2006; 7(2): 268 - 285.
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Cancer Res.Home page
F. Lopez-Rios, S. Chuai, R. Flores, S. Shimizu, T. Ohno, K. Wakahara, P. B. Illei, S. Hussain, L. Krug, M. F. Zakowski, et al.
Global Gene Expression Profiling of Pleural Mesotheliomas: Overexpression of Aurora Kinases and P16/CDKN2A Deletion as Prognostic Factors and Critical Evaluation of Microarray-Based Prognostic Prediction.
Cancer Res., March 15, 2006; 66(6): 2970 - 2979.
[Abstract] [Full Text] [PDF]


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J. Clin. Pathol.Home page
J S Reis-Filho, C Westbury, and J-Y Pierga
The impact of expression profiling on prognostic and predictive testing in breast cancer.
J. Clin. Pathol., March 1, 2006; 59(3): 225 - 231.
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JCOHome page
I. S. Lossos and D. Morgensztern
Prognostic Biomarkers in Diffuse Large B-Cell Lymphoma
J. Clin. Oncol., February 20, 2006; 24(6): 995 - 1007.
[Abstract] [Full Text] [PDF]


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Cancer Res.Home page
P. Roepman, P. Kemmeren, L. F.A. Wessels, P. J. Slootweg, and F. C.P. Holstege
Multiple Robust Signatures for Detecting Lymph Node Metastasis in Head and Neck Cancer
Cancer Res., February 15, 2006; 66(4): 2361 - 2366.
[Abstract] [Full Text] [PDF]


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Clin. Cancer Res.Home page
S. P. Linke, T. M. Bremer, C. D. Herold, G. Sauter, and C. Diamond
A Multimarker Model to Predict Outcome in Tamoxifen-Treated Breast Cancer Patients
Clin. Cancer Res., February 15, 2006; 12(4): 1175 - 1183.
[Abstract] [Full Text] [PDF]


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JCOHome page
J. D. Brenton, A. A. Ahmed, and C. Caldas
In Reply:
J. Clin. Oncol., February 1, 2006; 24(4): 722 - 723.
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Clin TrialsHome page
S. G Baker, B. S Kramer, M. McIntosh, B. H Patterson, Y. Shyr, and S. Skates
Evaluating markers for the early detection of cancer: overview of study designs and methods
Clinical Trials, February 1, 2006; 3(1): 43 - 56.
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Clin. Cancer Res.Home page
F. Ambrogi, E. Biganzoli, P. Querzoli, S. Ferretti, P. Boracchi, S. Alberti, E. Marubini, and I. Nenci
Molecular Subtyping of Breast Cancer from Traditional Tumor Marker Profiles Using Parallel Clustering Methods
Clin. Cancer Res., February 1, 2006; 12(3): 781 - 790.
[Abstract] [Full Text] [PDF]


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BioinformaticsHome page
Y. Tan, L. Shi, S. M. Hussain, J. Xu, W. Tong, J. M. Frazier, and C. Wang
Integrating time-course microarray gene expression profiles with cytotoxicity for identification of biomarkers in primary rat hepatocytes exposed to cadmium
Bioinformatics, January 1, 2006; 22(1): 77 - 87.
[Abstract] [Full Text] [PDF]


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Clin. Cancer Res.Home page
S. M. Lin and W. A. Kibbe
Irrational Exuberance in Clinical Proteomics
Clin. Cancer Res., November 15, 2005; 11(22): 7963 - 7964.
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Clin. Cancer Res.Home page
F. De Smet, N. L.M.M. Pochet, B. L.R. De Moor, T. Van Gorp, D. Timmerman, I. B. Vergote, L. C. Hartmann, A. I. Damokosh, and S. Hoersch
Independent Test Set Performance in the Prediction of Early Relapse in Ovarian Cancer with Gene Expression Profiles
Clin. Cancer Res., November 1, 2005; 11(21): 7958 - 7959.
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JCOHome page
J. D. Brenton, L. A. Carey, A. A. Ahmed, and C. Caldas
Molecular Classification and Molecular Forecasting of Breast Cancer: Ready for Clinical Application?
J. Clin. Oncol., October 10, 2005; 23(29): 7350 - 7360.
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JCOHome page
R. Simon
Roadmap for Developing and Validating Therapeutically Relevant Genomic Classifiers
J. Clin. Oncol., October 10, 2005; 23(29): 7332 - 7341.
[Abstract] [Full Text] [PDF]


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Molecular Cancer TherapeuticsHome page
D. W. Mount and R. Pandey
Using bioinformatics and genome analysis for new therapeutic interventions
Mol. Cancer Ther., October 1, 2005; 4(10): 1636 - 1643.
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BioinformaticsHome page
L. F. A. Wessels, M. J. T. Reinders, A. A. M. Hart, C. J. Veenman, H. Dai, Y. D. He, and L. J. v. Veer
A protocol for building and evaluating predictors of disease state based on microarray data
Bioinformatics, October 1, 2005; 21(19): 3755 - 3762.
[Abstract] [Full Text] [PDF]


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Cancer Res.Home page
T.-K. Man, M. Chintagumpala, J. Visvanathan, J. Shen, L. Perlaky, J. Hicks, M. Johnson, N. Davino, J. Murray, L. Helman, et al.
Expression Profiles of Osteosarcoma That Can Predict Response to Chemotherapy
Cancer Res., September 15, 2005; 65(18): 8142 - 8150.
[Abstract] [Full Text] [PDF]


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Physiol. GenomicsHome page
R. A. Jolly, K. M. Goldstein, T. Wei, H. Gao, P. Chen, S. Huang, J.-M. Colet, T. P. Ryan, C. E. Thomas, and S. T. Estrem
Pooling samples within microarray studies: a comparative analysis of rat liver transcription response to prototypical toxicants
Physiol Genomics, August 11, 2005; 22(3): 346 - 355.
[Abstract] [Full Text] [PDF]


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BioinformaticsHome page
A. M. Molinaro, R. Simon, and R. M. Pfeiffer
Prediction error estimation: a comparison of resampling methods
Bioinformatics, August 1, 2005; 21(15): 3301 - 3307.
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Nucleic Acids ResHome page
J. M. Vaquerizas, L. Conde, P. Yankilevich, A. Cabezon, P. Minguez, R. Diaz-Uriarte, F. Al-Shahrour, J. Herrero, and J. Dopazo
GEPAS, an experiment-oriented pipeline for the analysis of microarray gene expression data
Nucleic Acids Res., July 1, 2005; 33(suppl_2): W616 - W620.
[Abstract] [Full Text] [PDF]


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JNCI J Natl Cancer InstHome page
R. Simon
Development and Validation of Therapeutically Relevant Multi-Gene Biomarker Classifiers
J Natl Cancer Inst, June 15, 2005; 97(12): 866 - 867.
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JNCI J Natl Cancer InstHome page
J. F. Reid, L. Lusa, L. De Cecco, D. Coradini, S. Veneroni, M. G. Daidone, M. Gariboldi, and M. A. Pierotti
Limits of Predictive Models Using Microarray Data for Breast Cancer Clinical Treatment Outcome
J Natl Cancer Inst, June 15, 2005; 97(12): 927 - 930.
[Abstract] [Full Text] [PDF]


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JCOHome page
J. Hannemann, H. M. Oosterkamp, C. A.J. Bosch, A. Velds, L. F.A. Wessels, C. Loo, E. J. Rutgers, S. Rodenhuis, and M. J. van de Vijver
Changes in Gene Expression Associated With Response to Neoadjuvant Chemotherapy in Breast Cancer
J. Clin. Oncol., May 20, 2005; 23(15): 3331 - 3342.
[Abstract] [Full Text] [PDF]


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J. Mol. Diagn.Home page
L. True and Z. Feng
Immunohistochemical Validation of Expression Microarray Results
J. Mol. Diagn., May 1, 2005; 7(2): 149 - 151.
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Cancer Res.Home page
N. Hu, C. Wang, Y. Hu, H. H. Yang, C. Giffen, Z.-Z. Tang, X.-Y. Han, A. M. Goldstein, M. R. Emmert-Buck, K. H. Buetow, et al.
Genome-Wide Association Study in Esophageal Cancer Using GeneChip Mapping 10K Array
Cancer Res., April 1, 2005; 65(7): 2542 - 2546.
[Abstract] [Full Text] [PDF]


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JCOHome page
B. M. Ghadimi, M. Grade, M. J. Difilippantonio, S. Varma, R. Simon, C. Montagna, L. Fuzesi, C. Langer, H. Becker, T. Liersch, et al.
Effectiveness of Gene Expression Profiling for Response Prediction of Rectal Adenocarcinomas to Preoperative Chemoradiotherapy
J. Clin. Oncol., March 20, 2005; 23(9): 1826 - 1838.
[Abstract] [Full Text] [PDF]