runDeMAND: Run DeMAND algorithm
In DeMAND: DeMAND
Description
Usage
Arguments
Details
Value
Examples
Description
DeMAND.
This function is based on the realization that drugs affect the protein activity of their targets, but not necessarily their mRNA expression levels. In contrast, the change in protein activity directly affects the mRNA expression levels of downstream genes. Based on this hypothesis, DeMAND identifies drug MoA by comparing gene expression profiles following drug perturbation with control samples, and computing the change in the individual interactions within a pre-determined integrated transcriptional and post-translational regulatory model (interactome).
Usage
1
2
Arguments
x
An instance of class demand which includes: a gene expression data, annotation information, and a molecular interaction network.
fgIndex
A numeric vector contains indices of columns which represent case samples (e.g. drug treated). The sample size should be greater than 3.
bgIndex
A numeric vector contains indices of columns which represent control samples (e.g. drug treated). The sample size should be greater than 3.
verbose
A boolean value (TRUE by defalut) indicating whether to print progression outputs
method
A string value indicating whether to evaluate the KL-divergence using grid points based on 'bandwidth' (default) or on the 'integers' space
keepLeaves
A boolean value indicating whether to return a p-value for genes the have only a single neighbor in the network (default is FALSE, which returns 1 for such genes)
alpha
The cutoff for estimating a p-value using pareto fitting (default=0.05)
Details
For each edge in the interactome we determine the two-dimensional probability distribution of the gene expression levels both in the control state, and following drug treatment. Any changes in the probability distribution are estimated using the Kullback-Leibler (KL) divergence, from which we determine the statistical significance of the dysregulation of each edge. In the second step of DeMAND, we interrogate each gene independently to determine whether its interactions are enriched in dysregulated ones, suggesting that it is a candidate mechanism of action.
Value
Returns a DeMAND class object holding the same exp, anno, and network slots as the input, and where the moa and KLD slots hold the results of DeMAND algorithm. The moa slot is a matrix containing a list of genes, corresponding p-value, and adjusted p-value. The KLD slot is a matrix with the gene names of the edges that were evaluated, their KL-divergence, and the p-value assigned to that divergence.
Examples
1
2
3
4
5
6
7
8
9
## Load toy example
data(inputExample)
dobj <- demandClass(exp=bcellExp, anno=bcellAnno, network=bcellNetwork, moa=NULL)
dobj <- runDeMAND(dobj, fgIndex=caseIndex, bgIndex=controlIndex)
## results (head)
printDeMAND(dobj)
## results (all)
print(dobj@moa)
print(dobj@KLD)
Example output
Loading required package: KernSmooth
KernSmooth 2.23 loaded
Copyright M. P. Wand 1997-2009
Pruning the network
Keeping best probe per gene
Make a null distribution for KL divergence.....
Measure dysregulation of the interactions.....
Estimate dysregulation of the genes.....
An object of class demand
Slot exp:
Expression data of 1577 features by 12 samples
Slot anno:
Annotation of 1577 probes and 452 genes
Slot network:
Interactome with 2684 nodes, 1577 edges
Slot moa (head):
moaGene Pvalue FDR
HSP90AB1 3.714804e-18 3.083287e-16
HSP90AA1 5.726617e-17 2.376546e-15
PRKDC 2.042684e-03 5.651425e-02
AKT1 4.080922e-03 5.745073e-02
CREB1 4.584606e-03 5.745073e-02
IKBKB 5.202981e-03 5.745073e-02
Slot KLD (head):
gene1 gene2 KLD KLD.p
HSP90AB1 MDH1 19.4234259772248 0.00547210211486877
HSP90AB1 MYC 18.7243522480777 0.0059419263899117
HSP90AA1 HSPA8 18.3680838814313 0.00620405229240995
ESR1 HSP90AB1 17.4293319382159 0.00698028911166881
HSP90AB1 PRKDC 15.910295299091 0.00856776833271368
HSP90AB1 TBX5 15.1001135358549 0.00963550482164556
moaGene Pvalue FDR
1 HSP90AB1 3.714804e-18 3.083287e-16
2 HSP90AA1 5.726617e-17 2.376546e-15
3 PRKDC 2.042684e-03 5.651425e-02
4 AKT1 4.080922e-03 5.745073e-02
5 CREB1 4.584606e-03 5.745073e-02
6 IKBKB 5.202981e-03 5.745073e-02
7 CDK4 5.447036e-03 5.745073e-02
8 MYC 6.036180e-03 5.745073e-02
9 ESR1 6.438634e-03 5.745073e-02
10 TP53 6.921775e-03 5.745073e-02
11 POU2F2 9.634514e-03 7.269678e-02
12 E2F4 1.111305e-02 7.686525e-02
13 RBL2 6.530193e-02 4.169277e-01
14 FOXM1 8.458963e-02 5.014957e-01
15 E2F5 9.932309e-01 1.000000e+00
16 AHR 1.000000e+00 1.000000e+00
17 AKT2 1.000000e+00 1.000000e+00
18 CSNK2A2 1.000000e+00 1.000000e+00
19 ERBB2 1.000000e+00 1.000000e+00
20 PTK2B 1.000000e+00 1.000000e+00
21 FKBP4 1.000000e+00 1.000000e+00
22 FKBP5 1.000000e+00 1.000000e+00
23 GNA12 1.000000e+00 1.000000e+00
24 NR3C1 1.000000e+00 1.000000e+00
25 HIF1A 1.000000e+00 1.000000e+00
26 HSPA8 1.000000e+00 1.000000e+00
27 STAT1 1.000000e+00 1.000000e+00
28 ACTB 1.000000e+00 1.000000e+00
29 FOXO3 1.000000e+00 1.000000e+00
30 GNAI2 1.000000e+00 1.000000e+00
31 MAF 1.000000e+00 1.000000e+00
32 POU4F1 1.000000e+00 1.000000e+00
33 SP3 1.000000e+00 1.000000e+00
34 TBX5 1.000000e+00 1.000000e+00
35 CREBBP 1.000000e+00 1.000000e+00
36 E2F1 1.000000e+00 1.000000e+00
37 ETS1 1.000000e+00 1.000000e+00
38 BHLHE40 1.000000e+00 1.000000e+00
39 PATZ1 1.000000e+00 1.000000e+00
40 MAPK1 1.000000e+00 1.000000e+00
41 SIM2 1.000000e+00 1.000000e+00
42 TOMM70A 1.000000e+00 1.000000e+00
43 CNKSR1 1.000000e+00 1.000000e+00
44 MDH1 1.000000e+00 1.000000e+00
45 RPS4X 1.000000e+00 1.000000e+00
46 SPTAN1 1.000000e+00 1.000000e+00
47 ATP6AP1 1.000000e+00 1.000000e+00
48 BUB1 1.000000e+00 1.000000e+00
49 BUB1B 1.000000e+00 1.000000e+00
50 CAV1 1.000000e+00 1.000000e+00
51 SERPINH1 1.000000e+00 1.000000e+00
52 CCNA2 1.000000e+00 1.000000e+00
53 CCNF 1.000000e+00 1.000000e+00
54 CSE1L 1.000000e+00 1.000000e+00
55 DNMT1 1.000000e+00 1.000000e+00
56 ENO1 1.000000e+00 1.000000e+00
57 EP300 1.000000e+00 1.000000e+00
58 HMGA1 1.000000e+00 1.000000e+00
59 IL1R1 1.000000e+00 1.000000e+00
60 STMN1 1.000000e+00 1.000000e+00
61 SMAD3 1.000000e+00 1.000000e+00
62 MCM2 1.000000e+00 1.000000e+00
63 MSN 1.000000e+00 1.000000e+00
64 MYCN 1.000000e+00 1.000000e+00
65 NDUFAB1 1.000000e+00 1.000000e+00
66 PPP1CC 1.000000e+00 1.000000e+00
67 RCN1 1.000000e+00 1.000000e+00
68 RDX 1.000000e+00 1.000000e+00
69 RRM2 1.000000e+00 1.000000e+00
70 TFDP1 1.000000e+00 1.000000e+00
71 TMPO 1.000000e+00 1.000000e+00
72 TOP2B 1.000000e+00 1.000000e+00
73 CCT3 1.000000e+00 1.000000e+00
74 UBE2G1 1.000000e+00 1.000000e+00
75 YWHAZ 1.000000e+00 1.000000e+00
76 MELK 1.000000e+00 1.000000e+00
77 ARL4C 1.000000e+00 1.000000e+00
78 PSMD14 1.000000e+00 1.000000e+00
79 SPAG5 1.000000e+00 1.000000e+00
80 TPX2 1.000000e+00 1.000000e+00
81 CYFIP2 1.000000e+00 1.000000e+00
82 PSMC3IP 1.000000e+00 1.000000e+00
83 CDT1 1.000000e+00 1.000000e+00
gene1 gene2 KLD KLD.p
1 HSP90AB1 MDH1 19.4234259772248 0.00547210211486877
2 HSP90AB1 MYC 18.7243522480777 0.0059419263899117
3 HSP90AA1 HSPA8 18.3680838814313 0.00620405229240995
4 ESR1 HSP90AB1 17.4293319382159 0.00698028911166881
5 HSP90AB1 PRKDC 15.910295299091 0.00856776833271368
6 HSP90AB1 TBX5 15.1001135358549 0.00963550482164556
7 HSP90AB1 IKBKB 15.0454266772567 0.00971438649373776
8 FOXO3 HSP90AB1 14.7602731694071 0.010141209947818
9 HSP90AB1 SP3 14.6291861862411 0.0103465579849686
10 HSP90AB1 SPTAN1 14.2384087145075 0.0109956256148826
11 HSP90AB1 MAF 14.1403881304229 0.0111676499390323
12 HSP90AB1 TP53 13.9105313268378 0.011586610579985
13 ACTB HSP90AB1 13.7111965482395 0.0119685794034815
14 E2F4 HSP90AA1 13.6960376423069 0.0119983683262241
15 HSP90AB1 POU2F2 13.6576765195396 0.0120742324537253
16 AKT1 HSP90AB1 13.5751414375101 0.0122398238003534
17 CREB1 HSP90AB1 13.3615986929628 0.0126837937962314
18 GNAI2 HSP90AB1 13.2619384089009 0.0128989904738761
19 HSP90AB1 RPS4X 13.1167192520202 0.0132221260609236
20 HSP90AA1 PRKDC 13.007527226705 0.0134728559687702
21 GNA12 HSP90AA1 12.6877821273894 0.0142478588195592
22 HSP90AB1 POU4F1 12.3134809607946 0.0152396152334998
23 HSP90AA1 RBL2 12.2650144057348 0.0153752768267376
24 HSP90AA1 TOMM70A 12.1382194282169 0.0157385487699292
25 AHR HSP90AA1 12.105324623905 0.0158348186932333
26 CDK4 HSP90AA1 11.8545695077292 0.0165974553952537
27 AKT1 HSP90AA1 10.3481820188388 0.0225255025605343
28 CNKSR1 HSP90AA1 10.152585360821 0.0235124488977735
29 CREB1 HSP90AA1 9.85018612875591 0.025165666012782
30 ERBB2 HSP90AA1 9.60113246975925 0.0266564068839502
31 HSP90AA1 TP53 9.4094996437683 0.0278918834808826
32 HSP90AA1 STAT1 8.82568470837104 0.0322099773470649
33 FOXM1 HSP90AA1 8.4244016769939 0.0357605864151592
34 HSP90AA1 IKBKB 8.14594726989446 0.0385662941353308
35 CSNK2A2 HSP90AA1 7.96595870340538 0.0405521240058848
36 HIF1A HSP90AA1 7.8748234985423 0.0416143685189775
37 HSP90AA1 SIM2 7.87249276455824 0.0416420598303788
38 AKT2 HSP90AA1 7.80282318751212 0.0424822476736377
39 FKBP4 HSP90AA1 7.42557494407697 0.0474865665644616
40 HSP90AA1 MYC 7.28338993969766 0.0495951656986884
41 CDK4 E2F5 7.17556884294093 0.0515826494724502
42 HSP90AA1 NR3C1 6.88501308440561 0.0527549824150059
43 HSP90AA1 PTK2B 6.85015648427049 0.0550996483001172
44 FKBP5 HSP90AA1 6.84411916680732 0.0550996483001172
45 HSP90AA1 MAPK1 6.77025529098011 0.05978898007034
46 HSP90AA1 POU2F2 6.4535609388508 0.0679953106682298
47 ESR1 HSP90AA1 6.1933803213501 0.0703399765533411
48 E2F5 RRM2 1.85393552740862 0.138335287221571
49 E2F5 IL1R1 1.79658873201682 0.143024618991794
50 E2F4 E2F5 1.69211443401137 0.153575615474795
51 E2F5 ENO1 1.21000382341274 0.225087924970692
52 E2F5 ETS1 1.14696076171713 0.23915592028136
53 E2F5 SMAD3 1.07497750342221 0.259085580304807
54 E2F5 EP300 0.983235468112434 0.281359906213365
55 E2F5 HMGA1 0.945802905000695 0.294255568581477
56 E2F5 RCN1 0.7990164930481 0.355216881594373
57 E2F5 MYC 0.787063611620847 0.362250879249707
58 E2F5 TP53 0.724140779008721 0.397420867526378
59 E2F5 PPP1CC 0.691547887206775 0.412661195779601
60 BHLHE40 E2F5 0.589697657141508 0.475967174677608
61 E2F5 SERPINH1 0.584147889592148 0.480656506447831
62 E2F5 PSMC3IP 0.562166874879413 0.498241500586166
63 E2F5 FOXM1 0.557187300392008 0.504103165298945
64 BUB1B E2F5 0.55530068355236 0.505275498241501
65 ATP6AP1 E2F5 0.549969592813276 0.507620164126612
66 E2F5 TOP2B 0.537578123711192 0.52168815943728
67 E2F1 E2F5 0.531072412488992 0.527549824150059
68 E2F1 E2F5 0.531072412488992 0.527549824150059
69 E2F5 MCM2 0.472999241268294 0.582649472450176
70 CSE1L E2F5 0.472163582231899 0.583821805392732
71 E2F5 NDUFAB1 0.439746867902548 0.609613130128957
72 E2F5 MYCN 0.43857075728491 0.610785463071512
73 CCNF E2F5 0.362527474312986 0.678780773739742
74 CCT3 E2F5 0.356373484632021 0.685814771395076
75 E2F5 TMPO 0.352214335207929 0.690504103165299
76 E2F5 UBE2G1 0.346937194931746 0.696365767878077
77 ARL4C E2F5 0.345034556720999 0.7010550996483
78 E2F5 YWHAZ 0.337695051856575 0.704572098475967
79 CYFIP2 E2F5 0.330831835142842 0.710433763188746
80 CCNA2 E2F5 0.30200126905443 0.733880422039859
81 E2F5 STMN1 0.301297508536962 0.735052754982415
82 E2F5 TPX2 0.287096457749886 0.757327080890973
83 E2F5 SPAG5 0.276634784064457 0.772567409144197
84 CAV1 E2F5 0.268624835841128 0.786635404454865
85 E2F5 MELK 0.266064935449933 0.788980070339977
86 CDT1 E2F5 0.261130973082024 0.791324736225088
87 E2F5 PATZ1 0.234505597524228 0.81242672919109
88 E2F5 RBL2 0.192719221739987 0.866354044548652
89 E2F5 RDX 0.190863560910782 0.869871043376319
90 BUB1 E2F5 0.175347667768679 0.88862837045721
91 CREBBP E2F5 0.173255158205822 0.894490035169988
92 DNMT1 E2F5 0.169487881301203 0.903868698710434
93 E2F5 MSN 0.128031961494306 0.954279015240328
94 E2F5 TFDP1 0.126770088644898 0.954279015240328
95 E2F5 PSMD14 0.0919061931297625 0.98358733880422
DeMAND documentation built on Nov. 8, 2020, 8:22 p.m.
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Description Usage Arguments Details Value Examples
Description
DeMAND.
This function is based on the realization that drugs affect the protein activity of their targets, but not necessarily their mRNA expression levels. In contrast, the change in protein activity directly affects the mRNA expression levels of downstream genes. Based on this hypothesis, DeMAND identifies drug MoA by comparing gene expression profiles following drug perturbation with control samples, and computing the change in the individual interactions within a pre-determined integrated transcriptional and post-translational regulatory model (interactome).
Usage
1 2 |
Arguments
x |
An instance of class demand which includes: a gene expression data, annotation information, and a molecular interaction network. |
fgIndex |
A numeric vector contains indices of columns which represent case samples (e.g. drug treated). The sample size should be greater than 3. |
bgIndex |
A numeric vector contains indices of columns which represent control samples (e.g. drug treated). The sample size should be greater than 3. |
verbose |
A boolean value (TRUE by defalut) indicating whether to print progression outputs |
method |
A string value indicating whether to evaluate the KL-divergence using grid points based on |
keepLeaves |
A boolean value indicating whether to return a p-value for genes the have only a single neighbor in the network (default is FALSE, which returns 1 for such genes) |
alpha |
The cutoff for estimating a p-value using pareto fitting (default=0.05) |
Details
For each edge in the interactome we determine the two-dimensional probability distribution of the gene expression levels both in the control state, and following drug treatment. Any changes in the probability distribution are estimated using the Kullback-Leibler (KL) divergence, from which we determine the statistical significance of the dysregulation of each edge. In the second step of DeMAND, we interrogate each gene independently to determine whether its interactions are enriched in dysregulated ones, suggesting that it is a candidate mechanism of action.
Value
Returns a DeMAND class object holding the same exp, anno, and network slots as the input, and where the moa and KLD slots hold the results of DeMAND algorithm. The moa slot is a matrix containing a list of genes, corresponding p-value, and adjusted p-value. The KLD slot is a matrix with the gene names of the edges that were evaluated, their KL-divergence, and the p-value assigned to that divergence.
Examples
1 2 3 4 5 6 7 8 9 | ## Load toy example
data(inputExample)
dobj <- demandClass(exp=bcellExp, anno=bcellAnno, network=bcellNetwork, moa=NULL)
dobj <- runDeMAND(dobj, fgIndex=caseIndex, bgIndex=controlIndex)
## results (head)
printDeMAND(dobj)
## results (all)
print(dobj@moa)
print(dobj@KLD)
|
Example output
Loading required package: KernSmooth
KernSmooth 2.23 loaded
Copyright M. P. Wand 1997-2009
Pruning the network
Keeping best probe per gene
Make a null distribution for KL divergence.....
Measure dysregulation of the interactions.....
Estimate dysregulation of the genes.....
An object of class demand
Slot exp:
Expression data of 1577 features by 12 samples
Slot anno:
Annotation of 1577 probes and 452 genes
Slot network:
Interactome with 2684 nodes, 1577 edges
Slot moa (head):
moaGene Pvalue FDR
HSP90AB1 3.714804e-18 3.083287e-16
HSP90AA1 5.726617e-17 2.376546e-15
PRKDC 2.042684e-03 5.651425e-02
AKT1 4.080922e-03 5.745073e-02
CREB1 4.584606e-03 5.745073e-02
IKBKB 5.202981e-03 5.745073e-02
Slot KLD (head):
gene1 gene2 KLD KLD.p
HSP90AB1 MDH1 19.4234259772248 0.00547210211486877
HSP90AB1 MYC 18.7243522480777 0.0059419263899117
HSP90AA1 HSPA8 18.3680838814313 0.00620405229240995
ESR1 HSP90AB1 17.4293319382159 0.00698028911166881
HSP90AB1 PRKDC 15.910295299091 0.00856776833271368
HSP90AB1 TBX5 15.1001135358549 0.00963550482164556
moaGene Pvalue FDR
1 HSP90AB1 3.714804e-18 3.083287e-16
2 HSP90AA1 5.726617e-17 2.376546e-15
3 PRKDC 2.042684e-03 5.651425e-02
4 AKT1 4.080922e-03 5.745073e-02
5 CREB1 4.584606e-03 5.745073e-02
6 IKBKB 5.202981e-03 5.745073e-02
7 CDK4 5.447036e-03 5.745073e-02
8 MYC 6.036180e-03 5.745073e-02
9 ESR1 6.438634e-03 5.745073e-02
10 TP53 6.921775e-03 5.745073e-02
11 POU2F2 9.634514e-03 7.269678e-02
12 E2F4 1.111305e-02 7.686525e-02
13 RBL2 6.530193e-02 4.169277e-01
14 FOXM1 8.458963e-02 5.014957e-01
15 E2F5 9.932309e-01 1.000000e+00
16 AHR 1.000000e+00 1.000000e+00
17 AKT2 1.000000e+00 1.000000e+00
18 CSNK2A2 1.000000e+00 1.000000e+00
19 ERBB2 1.000000e+00 1.000000e+00
20 PTK2B 1.000000e+00 1.000000e+00
21 FKBP4 1.000000e+00 1.000000e+00
22 FKBP5 1.000000e+00 1.000000e+00
23 GNA12 1.000000e+00 1.000000e+00
24 NR3C1 1.000000e+00 1.000000e+00
25 HIF1A 1.000000e+00 1.000000e+00
26 HSPA8 1.000000e+00 1.000000e+00
27 STAT1 1.000000e+00 1.000000e+00
28 ACTB 1.000000e+00 1.000000e+00
29 FOXO3 1.000000e+00 1.000000e+00
30 GNAI2 1.000000e+00 1.000000e+00
31 MAF 1.000000e+00 1.000000e+00
32 POU4F1 1.000000e+00 1.000000e+00
33 SP3 1.000000e+00 1.000000e+00
34 TBX5 1.000000e+00 1.000000e+00
35 CREBBP 1.000000e+00 1.000000e+00
36 E2F1 1.000000e+00 1.000000e+00
37 ETS1 1.000000e+00 1.000000e+00
38 BHLHE40 1.000000e+00 1.000000e+00
39 PATZ1 1.000000e+00 1.000000e+00
40 MAPK1 1.000000e+00 1.000000e+00
41 SIM2 1.000000e+00 1.000000e+00
42 TOMM70A 1.000000e+00 1.000000e+00
43 CNKSR1 1.000000e+00 1.000000e+00
44 MDH1 1.000000e+00 1.000000e+00
45 RPS4X 1.000000e+00 1.000000e+00
46 SPTAN1 1.000000e+00 1.000000e+00
47 ATP6AP1 1.000000e+00 1.000000e+00
48 BUB1 1.000000e+00 1.000000e+00
49 BUB1B 1.000000e+00 1.000000e+00
50 CAV1 1.000000e+00 1.000000e+00
51 SERPINH1 1.000000e+00 1.000000e+00
52 CCNA2 1.000000e+00 1.000000e+00
53 CCNF 1.000000e+00 1.000000e+00
54 CSE1L 1.000000e+00 1.000000e+00
55 DNMT1 1.000000e+00 1.000000e+00
56 ENO1 1.000000e+00 1.000000e+00
57 EP300 1.000000e+00 1.000000e+00
58 HMGA1 1.000000e+00 1.000000e+00
59 IL1R1 1.000000e+00 1.000000e+00
60 STMN1 1.000000e+00 1.000000e+00
61 SMAD3 1.000000e+00 1.000000e+00
62 MCM2 1.000000e+00 1.000000e+00
63 MSN 1.000000e+00 1.000000e+00
64 MYCN 1.000000e+00 1.000000e+00
65 NDUFAB1 1.000000e+00 1.000000e+00
66 PPP1CC 1.000000e+00 1.000000e+00
67 RCN1 1.000000e+00 1.000000e+00
68 RDX 1.000000e+00 1.000000e+00
69 RRM2 1.000000e+00 1.000000e+00
70 TFDP1 1.000000e+00 1.000000e+00
71 TMPO 1.000000e+00 1.000000e+00
72 TOP2B 1.000000e+00 1.000000e+00
73 CCT3 1.000000e+00 1.000000e+00
74 UBE2G1 1.000000e+00 1.000000e+00
75 YWHAZ 1.000000e+00 1.000000e+00
76 MELK 1.000000e+00 1.000000e+00
77 ARL4C 1.000000e+00 1.000000e+00
78 PSMD14 1.000000e+00 1.000000e+00
79 SPAG5 1.000000e+00 1.000000e+00
80 TPX2 1.000000e+00 1.000000e+00
81 CYFIP2 1.000000e+00 1.000000e+00
82 PSMC3IP 1.000000e+00 1.000000e+00
83 CDT1 1.000000e+00 1.000000e+00
gene1 gene2 KLD KLD.p
1 HSP90AB1 MDH1 19.4234259772248 0.00547210211486877
2 HSP90AB1 MYC 18.7243522480777 0.0059419263899117
3 HSP90AA1 HSPA8 18.3680838814313 0.00620405229240995
4 ESR1 HSP90AB1 17.4293319382159 0.00698028911166881
5 HSP90AB1 PRKDC 15.910295299091 0.00856776833271368
6 HSP90AB1 TBX5 15.1001135358549 0.00963550482164556
7 HSP90AB1 IKBKB 15.0454266772567 0.00971438649373776
8 FOXO3 HSP90AB1 14.7602731694071 0.010141209947818
9 HSP90AB1 SP3 14.6291861862411 0.0103465579849686
10 HSP90AB1 SPTAN1 14.2384087145075 0.0109956256148826
11 HSP90AB1 MAF 14.1403881304229 0.0111676499390323
12 HSP90AB1 TP53 13.9105313268378 0.011586610579985
13 ACTB HSP90AB1 13.7111965482395 0.0119685794034815
14 E2F4 HSP90AA1 13.6960376423069 0.0119983683262241
15 HSP90AB1 POU2F2 13.6576765195396 0.0120742324537253
16 AKT1 HSP90AB1 13.5751414375101 0.0122398238003534
17 CREB1 HSP90AB1 13.3615986929628 0.0126837937962314
18 GNAI2 HSP90AB1 13.2619384089009 0.0128989904738761
19 HSP90AB1 RPS4X 13.1167192520202 0.0132221260609236
20 HSP90AA1 PRKDC 13.007527226705 0.0134728559687702
21 GNA12 HSP90AA1 12.6877821273894 0.0142478588195592
22 HSP90AB1 POU4F1 12.3134809607946 0.0152396152334998
23 HSP90AA1 RBL2 12.2650144057348 0.0153752768267376
24 HSP90AA1 TOMM70A 12.1382194282169 0.0157385487699292
25 AHR HSP90AA1 12.105324623905 0.0158348186932333
26 CDK4 HSP90AA1 11.8545695077292 0.0165974553952537
27 AKT1 HSP90AA1 10.3481820188388 0.0225255025605343
28 CNKSR1 HSP90AA1 10.152585360821 0.0235124488977735
29 CREB1 HSP90AA1 9.85018612875591 0.025165666012782
30 ERBB2 HSP90AA1 9.60113246975925 0.0266564068839502
31 HSP90AA1 TP53 9.4094996437683 0.0278918834808826
32 HSP90AA1 STAT1 8.82568470837104 0.0322099773470649
33 FOXM1 HSP90AA1 8.4244016769939 0.0357605864151592
34 HSP90AA1 IKBKB 8.14594726989446 0.0385662941353308
35 CSNK2A2 HSP90AA1 7.96595870340538 0.0405521240058848
36 HIF1A HSP90AA1 7.8748234985423 0.0416143685189775
37 HSP90AA1 SIM2 7.87249276455824 0.0416420598303788
38 AKT2 HSP90AA1 7.80282318751212 0.0424822476736377
39 FKBP4 HSP90AA1 7.42557494407697 0.0474865665644616
40 HSP90AA1 MYC 7.28338993969766 0.0495951656986884
41 CDK4 E2F5 7.17556884294093 0.0515826494724502
42 HSP90AA1 NR3C1 6.88501308440561 0.0527549824150059
43 HSP90AA1 PTK2B 6.85015648427049 0.0550996483001172
44 FKBP5 HSP90AA1 6.84411916680732 0.0550996483001172
45 HSP90AA1 MAPK1 6.77025529098011 0.05978898007034
46 HSP90AA1 POU2F2 6.4535609388508 0.0679953106682298
47 ESR1 HSP90AA1 6.1933803213501 0.0703399765533411
48 E2F5 RRM2 1.85393552740862 0.138335287221571
49 E2F5 IL1R1 1.79658873201682 0.143024618991794
50 E2F4 E2F5 1.69211443401137 0.153575615474795
51 E2F5 ENO1 1.21000382341274 0.225087924970692
52 E2F5 ETS1 1.14696076171713 0.23915592028136
53 E2F5 SMAD3 1.07497750342221 0.259085580304807
54 E2F5 EP300 0.983235468112434 0.281359906213365
55 E2F5 HMGA1 0.945802905000695 0.294255568581477
56 E2F5 RCN1 0.7990164930481 0.355216881594373
57 E2F5 MYC 0.787063611620847 0.362250879249707
58 E2F5 TP53 0.724140779008721 0.397420867526378
59 E2F5 PPP1CC 0.691547887206775 0.412661195779601
60 BHLHE40 E2F5 0.589697657141508 0.475967174677608
61 E2F5 SERPINH1 0.584147889592148 0.480656506447831
62 E2F5 PSMC3IP 0.562166874879413 0.498241500586166
63 E2F5 FOXM1 0.557187300392008 0.504103165298945
64 BUB1B E2F5 0.55530068355236 0.505275498241501
65 ATP6AP1 E2F5 0.549969592813276 0.507620164126612
66 E2F5 TOP2B 0.537578123711192 0.52168815943728
67 E2F1 E2F5 0.531072412488992 0.527549824150059
68 E2F1 E2F5 0.531072412488992 0.527549824150059
69 E2F5 MCM2 0.472999241268294 0.582649472450176
70 CSE1L E2F5 0.472163582231899 0.583821805392732
71 E2F5 NDUFAB1 0.439746867902548 0.609613130128957
72 E2F5 MYCN 0.43857075728491 0.610785463071512
73 CCNF E2F5 0.362527474312986 0.678780773739742
74 CCT3 E2F5 0.356373484632021 0.685814771395076
75 E2F5 TMPO 0.352214335207929 0.690504103165299
76 E2F5 UBE2G1 0.346937194931746 0.696365767878077
77 ARL4C E2F5 0.345034556720999 0.7010550996483
78 E2F5 YWHAZ 0.337695051856575 0.704572098475967
79 CYFIP2 E2F5 0.330831835142842 0.710433763188746
80 CCNA2 E2F5 0.30200126905443 0.733880422039859
81 E2F5 STMN1 0.301297508536962 0.735052754982415
82 E2F5 TPX2 0.287096457749886 0.757327080890973
83 E2F5 SPAG5 0.276634784064457 0.772567409144197
84 CAV1 E2F5 0.268624835841128 0.786635404454865
85 E2F5 MELK 0.266064935449933 0.788980070339977
86 CDT1 E2F5 0.261130973082024 0.791324736225088
87 E2F5 PATZ1 0.234505597524228 0.81242672919109
88 E2F5 RBL2 0.192719221739987 0.866354044548652
89 E2F5 RDX 0.190863560910782 0.869871043376319
90 BUB1 E2F5 0.175347667768679 0.88862837045721
91 CREBBP E2F5 0.173255158205822 0.894490035169988
92 DNMT1 E2F5 0.169487881301203 0.903868698710434
93 E2F5 MSN 0.128031961494306 0.954279015240328
94 E2F5 TFDP1 0.126770088644898 0.954279015240328
95 E2F5 PSMD14 0.0919061931297625 0.98358733880422
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