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Deep epistasis in human metabolism
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10.1063/1.3456056
/content/aip/journal/chaos/20/2/10.1063/1.3456056
http://aip.metastore.ingenta.com/content/aip/journal/chaos/20/2/10.1063/1.3456056

Figures

Image of FIG. 1.
FIG. 1.

A relaxed flux cone is generated by pathway fragments that fulfill a subset of steady state requirements for metabolic network . With each new iteration of pathway fragment computation, provides an increasingly better overapproximation to the system’s actual feasible flux cone . Since any flux that is infeasible in is guaranteed to be infeasible in , we can use the analysis of pathway fragments generating to compute cut sets for a reaction .

Image of FIG. 2.
FIG. 2.

Histogram showing MCS cardinalities stratified across the four metabolite classes.

Image of FIG. 3.
FIG. 3.

Histogram showing number of MCSs discovered for each biosynthetic objective examined in our study.

Image of FIG. 4.
FIG. 4.

Histogram showing number of -essential reactions discovered for each biosynthetic objective tested in our study. A reaction is -essential for an objective if it contributes to at least one MCS for that objective. The number of reactions found to be 1-essential for each objective (by brute-force optimization) is shown in parentheses next to the metabolite label.

Image of FIG. 5.
FIG. 5.

Histogram showing number of compartments spanned by MCSs targeting the four metabolite classes. Frequencies are calibrated separately for each metabolite class.

Image of FIG. 6.
FIG. 6.

Histogram showing frequencies of metabolic subsystems among the MCSs found for the four classes of biosynthetic objectives. Frequencies are calibrated separately for each metabolite class.

Image of FIG. 7.
FIG. 7.

Histogram showing frequencies of metabolic subsystems employed by MCSs targeting the four metabolic classes analyzed in our study. Frequencies are calibrated separately for each metabolite class.

Image of FIG. 8.
FIG. 8.

Membership map depicting subsystem signatures for MCSs identified in this study and corresponding histogram for each. The sparsity pattern of each row in the map represents a unique combination of subsystems, and the histogram on the right depicts how many MCSs exist with that given signature.

Image of FIG. 9.
FIG. 9.

(a) Membership map depicting 97 MCS and corresponding network of reactions predicted to be -essential for mitochondrial fumarase (FUMm) flux. The sparsity pattern of each row in the map represents reaction membership in a single MCS. (b) In the corresponding network diagram, round shaded nodes represent species and labeled hyperedges represent network reactions. Abbreviations used in this figure are listed in Table I.

Tables

Generic image for table
Table I.

Flux and metabolite abbreviations in the fumarase MCS network. Suffixes “_c” and “_m” are added in the network diagram to denote cytoplasmic and mitochondrial compartments, respectively.

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/content/aip/journal/chaos/20/2/10.1063/1.3456056
2010-06-30
2014-04-19
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752b84549af89a08dbdd7fdb8b9568b5 journal.articlezxybnytfddd
Scitation: Deep epistasis in human metabolism
http://aip.metastore.ingenta.com/content/aip/journal/chaos/20/2/10.1063/1.3456056
10.1063/1.3456056
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