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Combined static and dynamic analysis for determining the quality of time-series expression profiles

Nature Biotechnology volume 23, pages 1503–1508 (2005)Cite this article

Abstract

Expression profiling of time-series experiments is widely used to study biological systems. However, determining the quality of the resulting profiles remains a fundamental problem. Because of inadequate sampling rates, the effect of arrest-and-release methods and loss of synchronization, the measurements obtained from a series of time points may not accurately represent the underlying expression profiles. To solve this, we propose an approach that combines time-series and static (average) expression data analysis—for each gene, we determine whether its temporal expression profile can be reconciled with its static expression levels. We show that by combining synchronized and unsynchronized human cell cycle data, we can identify many cycling genes that are missed when using only time-series data. The algorithm also correctly distinguishes cycling genes from genes that specifically react to an environmental stimulus even if they share similar temporal expression profiles. Experimental validation of these results shows the utility of this analytical approach for determining the accuracy of gene expression patterns.

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Figure 1: The CheckSum method.
Figure 2: Cell cycle and serum-response genes.
Figure 3: Experimental validation.

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Acknowledgements

We thank Tommi Jaakkola, Larry Wasserman, Naftali Kaminski and the anonymous reviewers for comments on earlier versions. Z.B.J. is partially funded by National Science Fund Foundation CAREER award 0448453 and by the Pennsylvania Department of Health.

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Authors and Affiliations

  1. Dept. Molecular Biology, Hebrew University Medical School, Jerusalem, 91120, Israel

    Itamar Simon & Zahava Siegfried

  2. School of Computer Science, Carnegie Mellon University, 5000 Forbes Ave., Pittsburgh, 15213, Pennsylvania, USA

    Jason Ernst & Ziv Bar-Joseph

  3. Department of Biology, Carnegie Mellon University, 5000 Forbes Ave., Pittsburgh, 15213, Pennsylvania, USA

    Ziv Bar-Joseph

Authors
  1. Itamar Simon
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  2. Zahava Siegfried
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  4. Ziv Bar-Joseph
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Correspondence to Ziv Bar-Joseph.

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Simon, I., Siegfried, Z., Ernst, J. et al. Combined static and dynamic analysis for determining the quality of time-series expression profiles. Nat Biotechnol 23, 1503–1508 (2005). https://doi.org/10.1038/nbt1164

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