Reconstructing the pathways of a cellular system from genome-scale signals by using matrix and tensor computations

被引:38
作者
Alter, O [1 ]
Golub, GH
机构
[1] Stanford Univ, Sci Comp & Computat Math Program, Stanford, CA 94305 USA
[2] Stanford Univ, Dept Comparat Biosci, Stanford, CA 94305 USA
[3] Univ Texas, Dept Biomed Engn, Austin, TX 78712 USA
[4] Univ Texas, Inst Mol & Cellular Biol, Austin, TX 78712 USA
关键词
DNA microarrays; eigenvalue decomposition; higher-order eigenvalue decomposition; pseudoinverse projection; yeast Saccharomyces cerevisiae cell cycle and mating;
D O I
10.1073/pnas.0509033102
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
We describe the use of the matrix eigenvalue decomposition (EVD) and pseudoinverse projection and a tensor higher-order EVD (HOEVD) in reconstructing the pathways that compose a cellular system from genome-scale nondirectional networks of correlations among the genes of the system. The EVD formulates a genes x genes network as a linear superposition of genes x genes decor-related and decoupled rank-1 subnetworks, which can be associated with functionally independent pathways. The integrative pseudoinverse projection of a network computed from a "data" signal onto a designated "basis" signal approximates the network as a linear superposition of only the subnetworks that are common to both signals and simulates observation of only the pathways that are manifest in both experiments. We define a comparative HOEVD that formulates a series of networks as linear superpositions of decorrelated rank-1 subnetworks and the rank-2 couplings among these subnetworks, which can be associated with independent pathways and the transitions among them common to all networks in the series or exclusive to a subset of the networks. Boolean functions of the discretized subnetworks and couplings highlight differential, i.e., pathway-dependent, relations among genes. We illustrate the EVD, pseudoinverse projection, and HOEVD of genome-scale networks with analyses of yeast DNA microarray data.
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页码:17559 / 17564
页数:6
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