The vast anatomic and physiologic complexity of the mammalian 辽阔的解剖学与生理学的哺乳动物的复杂性.docVIP

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The vast anatomic and physiologic complexity of the mammalian 辽阔的解剖学与生理学的哺乳动物的复杂性.doc

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The vast anatomic and physiologic complexity of the mammalian 辽阔的解剖学与生理学的哺乳动物的复杂性

Automated discovery of functional generality of human gene expression programs Georg K. Gerber1,2, Robin D. Dowell1, Tommi S. Jaakkola1, David K. Gifford1,3 1 MIT Department of Computer Science and Electrical Engineering, 32 Vassar Street, Cambridge, MA 02139. 2 Harvard-MIT Division of Health Sciences and Technology, 45 Carleton Street Room E25-519, Cambridge, MA 02139. 3 Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge MA 02142. Correspondence should be addressed to David Gifford (gifford@mit.edu), 32 Vassar Street G542, Cambridge, MA 02139. Telephone: (617) 253-6039. Abbreviations used in the text: Expression program (EP), Gene Ontology (GO), or Kyoto Encyclopedia of Genes and Genomes (KEGG), Markov Chain Monte Carlo (MCMC), non-negative matrix factorization (NMF), Peripheral blood mononuclear cell (PBMC), and Singular Value Decomposition (SVD). Abstract An important research problem in computational biology is the identification of expression programs, sets of co-expressed genes orchestrating normal or pathological processes, and the characterization of the functional breadth of these programs. The use of human expression data compendia for discovery of such programs presents several challenges, including: 1) cellular inhomogeneity within samples, 2) genetic and environmental variation across samples, 3) uncertainty in the numbers of programs and sample populations, and 4) temporal behavior. We developed GeneProgram, a new unsupervised Bayesian computational framework based on Hierarchical Dirichlet Processes that addresses each of the above challenges. GeneProgram uses expression data to simultaneously organize tissues into groups and genes into overlapping programs with consistent temporal behavior, to produce maps of expression programs, which are sorted by generality scores that exploit the automatically learned groupings. Using synthetic and real gene expression data, we showed that GeneProgram outperformed several popular