Statistical analysis of MPSS measurements: Application to the study of LPS-activated macrophage gene expression

G. A. Stolovitzky, A. Kundaje, G. A. Held, K. H. Duggar, C. D. Haudenschild, D. Zhou, T. J. Vasicek, K. D. Smith, A. Aderem, J. C. Roach

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

Abstract

Massively Parallel Signature Sequencing (MPSS), a recently developed high-throughput transcription profiling technology, has the ability to profile almost every transcript in a sample without requiring prior knowledge of the sequence of the transcribed genes. As is the case with DNA microarrays, effective data analysis depends crucially on understanding how noise affects measurements. We analyze the sources of noise in MPSS and present a quantitative model describing the variability between replicate MPSS assays. We use this model to construct statistical hypotheses that test whether an observed change in gene expression in a pair-wise comparison is significant. This analysis is then extended to the determination of the significance of changes in expression levels measured over the course of a time series of measurements. We apply these analytic techniques to the study of a time series of MPSS gene expression measurements on LPS-stimulated macrophages. To evaluate our statistical significance metrics, we compare our results with published data on macrophage activation measured by using Affymetrix GeneChips.

Original languageEnglish
Pages (from-to)1402-1407
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number5
DOIs
StatePublished - 1 Feb 2005
Externally publishedYes

Keywords

  • Noise model
  • Transcription profiling

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