Extending signalling pathways with protein-interaction networks. Application to apoptosis.


Extending signalling pathways with protein-interaction networks. Application to apoptosis.
Joan Planas-Iglesias, Emre Guney, Javier Garcia-Garcia, Kevin A. Robertson, Sobia Raza, Tom C. Freeman, Peter Ghazal and Baldo Oliva.
OMICS. 2012 May;16(5):245-56. Epub 2012 Mar 2. (PMID: 22385281)

STRING+ expansion network

(Orthology filter at JEV = 1e-15)

Here we present numerical results for STRING+ expansion network in which interactions with JEV > 1e-15 were removed. In the following sections we provide the numerals we used to compute the p-Value for our predictions. For the computation of p-Value we consider as candidates the set of nodes in the network with sensitivity higher than 95% and PPV above 90% in the 5-fold cross-validation assay. For each validation set we compute a p-Value describing the likelyhood of obtaining the subset of validated candidates from the total number of proteins in the network according to the sizes of the candidates set and the validation set. Thus, a different p-Value is obtained for each validation set (Keyword, ProMiner).The mean JEV of the candidates and a p-Value for the significance of the differences between the JEV distribution of the candidates and the rest of the nodes in the network is provided as well.



Individual scoring methods

Validation of candidates posed by each scoring method. First column shows the analyzed scoring method. Second column corresponds to the number of nodes that accomplished quality criteria in the requested scoring methods. Columns 3 to 5 show relevant parameters for Keyword validation: the number of validated candidates, the size of the validation set and the p-Value obtained. Columns 6 to 8 contain analogous information for ProMiner validation.


Scoring method Number of candidates Keyword validated candidates Keyword validation size Keyword validation p-Value ProMiner validated candidates ProMiner validation size ProMiner validation p-Value JEV mean JEV differences p-Value
FF 1071 139 584 1.494091e-73 69 297 5.249788e-36 5.645134e-18 2.856227e-21
SC 2865 206 584 2.761463e-62 78 297 5.125124e-17 4.495282e-18 < 1.000000e-323
ALD 2472 177 584 1.562437e-53 81 297 2.747102e-22 6.363329e-18 < 1.000000e-323
iALD 888 134 584 2.587557e-79 50 297 5.608687e-24 1.283797e-20 1.077855e-27

The relevance of sequence similarity between interologs is analyzed in orthology expanded networks by removing those predictions that do not achieve a certain JEV value. Tables corresponding to the orthology filtered versions of this network are available for several -log(JEV) filter thresholds.
To access the tables, follow links below:
none 2 5 10 15 20

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Cumulative combinations

Validation of candidates posed by all possible combinations of N scoring methods, where N is shown in the first column. Second column corresponds to the number of nodes that accomplished quality criteria in the requested scoring methods. Columns 3 to 5 show relevant parameters for Keyword validation: the number of validated candidates, the size of the validation set and the p-Value obtained. Columns 6 to 8 contain analogous information for ProMiner validation.


Number of scoring method Number of candidates Keyword validated candidates Keyword validation size Keyword validation p-Value ProMiner validated candidates ProMiner validation size ProMiner validation p-Value JEV mean JEV differences p-Value
4 79 24 584 4.785867e-56 15 297 3.622015e-35 0.000000e+00 3.882790e-69
3 257 53 584 1.857678e-93 34 297 5.805262e-60 4.608978e-20 1.012539e-196
2 1636 147 584 3.369859e-136 65 297 1.348761e-60 2.807912e-18 < 1.000000e-323
1 3657 251 584 1.499962e-148 96 297 2.759464e-57 2.370277e-18 < 1.000000e-323

The relevance of sequence similarity between interologs is analyzed in orthology expanded networks by removing those predictions that do not achieve a certain JEV value. Tables corresponding to the orthology filtered versions of this network are available for several -log(JEV) filter thresholds.
To access the tables, follow links below:
none 2 5 10 15 20

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All Vs all combinations

Validation of candidates posed by each combination of scoring methods. Columns contain relevant parameters for the computation of the p-Value. For each validation method these are: number of candidates posed by the combination of scoring mehtods, number of validated candidates and the p-Value itself. The relevant fields of each validation method are colored in green if the row corresponds to the best combination of scoring methods for the validation method. For best combination of scoring methods rows, links lead to the details of validated protein candidates (under validated candidates columns) or to the details of new protein candidates (under combination of scoring methods column). Signalling-related functions of candidates from best combinations of scoring methods are given in Supplementary table 2.


Combination of scoring methods Number of candidates Keyword validated candidates Keyword validation size Keyword validation p-Value ProMiner validated candidates ProMiner validation size ProMiner validation p-Value JEV mean JEV differences p-Value
SC, ALD 1266 75 584 5.996498e-78 50 297 2.353387e-52 3.490417e-18 < 1.000000e-323
SC, FF 267 45 584 1.847044e-78 36 297 8.046007e-63 6.977125e-19 8.926506e-199
SC, iALD 200 43 584 6.797523e-81 22 297 1.236021e-41 2.165290e-21 2.755472e-142
ALD, FF 220 38 584 9.928600e-70 30 297 3.852428e-55 5.384075e-20 4.997208e-175
ALD, iALD 143 36 584 1.509593e-73 15 297 4.997151e-31 7.660463e-25 1.390985e-107
FF, iALD 291 88 584 1.870561e-151 25 297 6.405927e-43 1.229453e-50 7.250199e-244
SC, ALD, FF 153 30 584 2.860396e-60 29 297 2.867018e-58 7.741807e-20 4.957386e-121
SC, ALD, iALD 112 30 584 7.456043e-65 15 297 1.039827e-32 9.780770e-25 3.010064e-84
SC, FF, iALD 129 35 584 2.761281e-73 20 297 5.512594e-42 0.000000e+00 3.196699e-112
ALD, FF, iALD 100 30 584 1.413332e-66 15 297 1.686778e-33 0.000000e+00 2.975710e-87
SC, ALD, FF, iALD 79 24 584 4.785867e-56 15 297 3.622015e-35 0.000000e+00 3.882790e-69

The relevance of sequence similarity between interologs is analyzed in orthology expanded networks by removing those predictions that do not achieve a certain JEV value. Tables corresponding to the orthology filtered versions of this network are available for several -log(JEV) filter thresholds.
To access the tables, follow links below:
none 2 5 10 15 20

Go to top of page

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