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Population-specific expression analysis (PSEA) reveals molecular changes in diseased brain

Nature Methods volume 8, pages 945–947 (2011)Cite this article

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Abstract

Human diseases are often accompanied by histological changes that confound interpretation of molecular analyses and identification of disease-related effects. We developed population-specific expression analysis (PSEA), a computational method of analyzing gene expression in samples of varying composition that can improve analyses of quantitative molecular data in many biological contexts. PSEA of brains from individuals with Huntington's disease revealed myelin-related abnormalities that were undetected using standard differential expression analysis.

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Figure 1: PSEA of human brain samples.
Figure 2: Comparison of population-specific and total expression change in tissue samples with cell-composition changes.

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Gene Expression Omnibus

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Acknowledgements

This work was funded by the Huntington's Disease Society of America, the Novartis Foundation and the Swiss National Science; Foundation. We thank L. Glauser for technical assistance; F. Brunet, S. Lengacher, I. Allamand, M. Marti, L. Claivaz, M. Delorenzi, T. Sengstag, D. Goldstein and S. Brahmachari for helpful discussions; B. Deplancke, J. Rougemont, I. Krier and M. Nalls for critically reading the manuscript; members of Vital-IT and the Swiss Institute of Bioinformatics for providing computing infrastructure, and members of the Lausanne DNA Array facility for assistance in processing microarray samples from primary cell cultures.

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  1. Alexandre Kuhn

    Present address: Present address: Laboratory of Microfluidics Systems Biology, Institute of Materials Research and Engineering, Singapore.,

Authors and Affiliations

  1. Laboratory of Functional Neurogenomics, Ecole Polytechnique Fédérale de Lausanne, Switzerland

    Alexandre Kuhn, Doris Thu & Ruth Luthi-Carter

  2. Department of Anatomy with Radiology and Centre for Brain Research, University of Auckland, New Zealand

    Henry J Waldvogel & Richard L M Faull

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  1. Alexandre Kuhn
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  2. Doris Thu
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  3. Henry J Waldvogel
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  4. Richard L M Faull
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  5. Ruth Luthi-Carter
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Contributions

A.K. developed and applied PSEA, performed experiments with cultured cells, and wrote the manuscript, with input from R.L.-C; D.T., H.J.W. and R.L.M.F. performed immunohistochemical experiments with brain sections; and R.L.-C. conceptualized the project and directed the study.

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Correspondence to Alexandre Kuhn.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–21, Supplementary Tables 1–15,17–18, Supplementary Data 1–7, Supplementary Discussion (PDF 7675 kb)

Supplementary Table 16

Standard differential expression analysis showing differential total expression (HD grade 1 versus control samples). (XLSX 3345 kb)

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Kuhn, A., Thu, D., Waldvogel, H. et al. Population-specific expression analysis (PSEA) reveals molecular changes in diseased brain. Nat Methods 8, 945–947 (2011). https://doi.org/10.1038/nmeth.1710

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