期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 99, 期 20, 页码 12975-12978出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.162468199
关键词
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资金
- NHGRI NIH HHS [K22 HG000047-01, HG00047-01, T32 HG000047, K22 HG000047] Funding Source: Medline
DNA microarrays are important devices for high throughput measurements of gene expression, but no rational foundation has been established for understanding the sources of within-chip statistical error. We designed a specialized chip and protocol to investigate the distribution and magnitude of within-chip errors and discovered that, as expected from theoretical expectations, measurement errors follow a Lorentzian-like distribution, which explains the widely observed but unexplained ill-reproducibility in microarray data. Using this specially designed chip, we examined a data set of repeated measurements to extract estimates of the distribution and magnitude of statistical errors in DNA microarray measurements. Using the common ratio of medians method, we find that the measurements follow a Lorentzian-like distribution, which is problematic for subsequent analysis. We show that a method of analysis dubbed median of ratios yields a more Gaussian-like distribution of errors. Finally, we show that the bootstrap algorithm can be used to extract the best estimates of the error in the measurement. Quantifying the statistical error in such measurements has important applications for estimating significance levels, clustering algorithms, and process optimization.
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