SupplementaryInformationfor:
Solvingtheinfluencemaximizationproblemrevealsregulatoryorganizationofthe
yeastcellcycle.
DavidLGibbs,IlyaShmulevich
SIFigure1.
SIFigure1.Similaritymetricsvarywithamountoftimelag.A.)Thetranscription
factorREB1interactswithMDH2.Expressionlevelsareshownacrossthreecell
cycleswhereeachtimepointequals5minutes.B.)Whentimelagsareintroduced,
inthisexample,thePearsoncorrelationbetweenthetwogenesdecreases.Transfer
entropyvaluesshowapeakatatimelagof3.
SIFigure2.
1000
Cover
750
500
250
0
10
20
K
30
40
SIFigure2.Influencescoreincreaseswiththenumberofsourcenodes(K).
S1Table.Toptwentyrankedinfluencersandassociatedcentralitymetrics.
Gene
Rank
Degree
InDegree
OutDegree
AlphaCentrality Betweenness
Ego2
Ego1
SubGraphCentr
PowerCentrality ality
SVD
FKH1
44
142
1
141
226.12
1168
257
143
3.31
0.00
0.045
GCN5
43
90
0
90
1.00
0
232
91
3.04
41.12
0.000
RFX1
43
75
0
75
1.00
0
171
76
11.92
65.25
0.000
STP1
42
82
0
82
1.00
0
100
83
1.06
79.17
0.000
BUR6
40
34
0
34
1.00
0
62
35
1.06
74.70
0.000
TFC7
39
97
0
97
1.00
0
167
98
1.96
65.42
0.000
RAP1
38
81
1
80
39.51
1886
309
82
6.73
0.00
0.023
SFP1
37
60
0
60
1.00
0
82
61
0.70
45.53
0.000
XBP1
36
32
0
32
1.00
0
52
33
0.76
26.83
0.000
YAP1
35
28
0
28
1.00
0
114
29
12.62
508.87
0.000
MBP1
34
60
0
60
1.00
0
155
61
11.92
16.75
0.000
IXR1
33
51
0
51
1.00
0
117
52
0.95
17.28
0.000
SUA7
32
16
0
16
1.00
0
24
17
0.19
14.00
0.000
ABF1
31
29
0
29
1.00
0
94
30
1.73
11.00
0.000
MSN2
30
36
0
36
1.00
0
89
37
0.51
12.83
0.000
SOK2
29
14
0
14
1.00
0
75
15
0.79
9.83
0.000
NRG1
28
21
0
21
1.00
0
64
22
0.41
11.58
0.000
CYC8
27
15
1
14
16.51
2103
230
16
9.04
0.00
0.018
MED4
27
10
0
10
1.00
0
19
11
0.12
8.75
0.000
STE12
26
11
0
11
1.00
0
35
12
0.13
8.00
0.000
Genesetenrichmentforfunctionalexploration
Todeterminegenesetfunctionalenrichment,over-representationtestingwasperformed
usingtheConsensusPathDBserviceutilizingahypergeometrictestoveralargecollectionof
pathwaysandgeneontology(GO)terms[REF].Mostofthecentralitymetrics,whicheach
hadroughly~30genes,producedFDRcorrectedsignificantpathwaysandGOtermresults
(Table2).TheKEGGcellcyclepathwaywasfrequentlyfoundsignificant,andcellcycle
relatedGOtermswerefound,butinlowrankingpositions.Severalmetrics,includingalpha
centralityandPageRank,returnedpoorresults,withnocellcyclerelatedtermsfound
significant.ChromatinremodelingandmetabolicrelatedpathwaysandGOtermswereoften
foundsignificant,emphasizingthecloserelationshipbetweenthecellcycle,metabolism,
andchromatinremodeling(S2Table).
Table 1. Pathway and GO term enrichement scores
Influence ranked genes pathway enrichment
p-value
q-value
source
pathway
1.06E-06
5.28E-06
KEGG
Cell cycle - yeast - Saccharomyces cerevisiae (budding yeast)
7.06E-05
0.000176504
Wikipathways
Cell Cycle and Cell Division
Influence Ranked genes GO term enrichment
p-value
q-value
term_goid
term_level
term_name
6.54E-24
4.12E-22
GO:0051171
4
regulation of nitrogen compound metabolic process
3.52E-23
1.11E-21
GO:0009889
4
regulation of biosynthetic process
7.25E-23
1.52E-21
GO:0034654
4
nucleobase-containing compound biosynthetic process
5.36E-22
8.45E-21
GO:0019438
4
aromatic compound biosynthetic process
8.33E-22
8.76E-21
GO:0060255
4
regulation of macromolecule metabolic process
Betweenness ranked genes GO term enrichment
p-value
q-value
term_goid
term_level
term_name
1.02E-24
8.27E-23
GO:0051171
4
regulation of nitrogen compound metabolic process
5.84E-24
2.36E-22
GO:0009889
4
regulation of biosynthetic process
1.23E-23
3.33E-22
GO:0034654
4
nucleobase-containing compound biosynthetic process
9.78E-23
1.98E-21
GO:0019438
4
aromatic compound biosynthetic process
1.54E-22
2.10E-21
GO:0060255
4
regulation of macromolecule metabolic process
InfoMap, Module 8
p-value
q-value
term_goid
term_level
term_name
2.70E-06
0.00012149
GO:0000278
4
mitotic cell cycle
4.03E-05
0.000907817
GO:0044770
4
cell cycle phase transition
6.92E-05
0.001038324
GO:0000083
4
regulation of transcription involved in G1/S phase of mitotic cell cy
0.000210038
0.001890344
GO:0030907
4
MBF transcription complex
0.000210038
0.001890344
GO:0033309
4
SBF transcription complex
AmongcellcyclerelatedGOterms,wefoundthatdifferentmetricscontained
differentfunctionalrelations.Incellcyclechronologicalorder,Ego2-stepand
Betweennessbothhad‘regulationoftranscriptioninvolvedinG1phaseofmitotic
cellcycle’,whilerankedinfluentialgenesshowed‘regulationoftranscription
involvedinG1/Sphaseofmitoticcellcycle’(GO:0000083).Betweennessshowed
significancewith‘regulationoftranscriptioninvolvedinG2/M-phaseofmitoticcell
cycle’(GO:0000117).