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Research Article

Metagenes and molecular pattern discovery using matrix factorization

Jean-Philippe Brunet, Pablo Tamayo, Todd R. Golub, and Jill P. Mesirov
  1. *The Eli and Edythe L. Broad Institute, Massachusetts Institute of Technology and Harvard University, 320 Charles Street, Cambridge, MA 02141; and †Dana–Farber Cancer Institute and Harvard Medical School, 44 Binney Street, Boston, MA 02115

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PNAS March 23, 2004 101 (12) 4164-4169; https://doi.org/10.1073/pnas.0308531101
Jean-Philippe Brunet
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Pablo Tamayo
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Todd R. Golub
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Jill P. Mesirov
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  1. Communicated by Eric S. Lander, Massachusetts Institute of Technology, Cambridge, MA, December 20, 2003 (received for review November 1, 2003)

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Abstract

We describe here the use of nonnegative matrix factorization (NMF), an algorithm based on decomposition by parts that can reduce the dimension of expression data from thousands of genes to a handful of metagenes. Coupled with a model selection mechanism, adapted to work for any stochastic clustering algorithm, NMF is an efficient method for identification of distinct molecular patterns and provides a powerful method for class discovery. We demonstrate the ability of NMF to recover meaningful biological information from cancer-related microarray data. NMF appears to have advantages over other methods such as hierarchical clustering or self-organizing maps. We found it less sensitive to a priori selection of genes or initial conditions and able to detect alternative or context-dependent patterns of gene expression in complex biological systems. This ability, similar to semantic polysemy in text, provides a general method for robust molecular pattern discovery.

Footnotes

    • ↵‡ To whom correspondence should be addressed. E-mail: mesirov{at}broad.mit.edu.

    • Abbreviations: NMF, nonnegative matrix factorization; HC, hierarchical clustering; SOM, self-organizing maps; AML, acute myelogenous leukemia; ALL, acute lymphoblastic leukemia.

    • Received November 1, 2003.
    • Copyright © 2004, The National Academy of Sciences
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    Metagenes and molecular pattern discovery using matrix factorization
    Jean-Philippe Brunet, Pablo Tamayo, Todd R. Golub, Jill P. Mesirov
    Proceedings of the National Academy of Sciences Mar 2004, 101 (12) 4164-4169; DOI: 10.1073/pnas.0308531101

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    Metagenes and molecular pattern discovery using matrix factorization
    Jean-Philippe Brunet, Pablo Tamayo, Todd R. Golub, Jill P. Mesirov
    Proceedings of the National Academy of Sciences Mar 2004, 101 (12) 4164-4169; DOI: 10.1073/pnas.0308531101
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    Proceedings of the National Academy of Sciences: 101 (12)
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