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Genome Biol. 2015 Mar 31;16:63. doi: 10.1186/s13059-015-0624-2.

An approach for determining and measuring network hierarchy applied to comparing the phosphorylome and the regulome.

Author information

1
Department of Genetics, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USA. chao.cheng@dartmouth.edu.
2
Institute for Quantitative Biomedical Sciences, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA. chao.cheng@dartmouth.edu.
3
Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA. chao.cheng@dartmouth.edu.
4
Department of Genetics, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USA. erik.h.andrews.med@dartmouth.edu.
5
Program in Computational Biology and Bioinformatics, Yale University, 260 Whitney Avenue, New Haven, CT, 06520, USA. koon-kiu.yan@yale.edu.
6
Department of Genetics, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USA. matthew.ung@dartmouth.edu.
7
Program in Computational Biology and Bioinformatics, Yale University, 260 Whitney Avenue, New Haven, CT, 06520, USA. daifeng.wang@yale.edu.
8
Program in Computational Biology and Bioinformatics, Yale University, 260 Whitney Avenue, New Haven, CT, 06520, USA. mark.gerstein@yale.edu.
9
Department of Molecular Biophysics and Biochemistry, Yale University, 260 Whitney Avenue, New Haven, CT, 06520, USA. mark.gerstein@yale.edu.
10
Department of Computer Science, Yale University, 260 Whitney Avenue, New Haven, CT, 06520, USA. mark.gerstein@yale.edu.

Abstract

Many biological networks naturally form a hierarchy with a preponderance of downward information flow. In this study, we define a score to quantify the degree of hierarchy in a network and develop a simulated-annealing algorithm to maximize the hierarchical score globally over a network. We apply our algorithm to determine the hierarchical structure of the phosphorylome in detail and investigate the correlation between its hierarchy and kinase properties. We also compare it to the regulatory network, finding that the phosphorylome is more hierarchical than the regulome.

PMID:
25880651
PMCID:
PMC4404648
DOI:
10.1186/s13059-015-0624-2
[Indexed for MEDLINE]
Free PMC Article

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