Submit

X2K Web infers upstream regulatory networks from signatures of differentially expressed genes. By combining transcription factor enrichment analysis, protein-protein interaction network expansion, with kinase enrichment analysis , X2K Web produces inferred networks of transcription factors, proteins, and kinases predicted to regulate the expression of the inputted gene list. X2K Web provides the results as tables and interactive vector graphic figures that can be readily embedded within publications.. You can read more about the X2K concept by reading the original X2K publication.




Enter a list of differentially expressed genes to receive results for:

  1. Putative enriched transcription factors through Transcription Factor Enrichment Analysis (TFEA).
  2. Protein–protein interactions subnetwork that connects the enriched transcription factors with known protein-protein interactions using the Genes2Networks (G2N) method.
  3. Ranked list of enriched kinases based on overlap between known kinase–substrate phosphorylation interactions and the proteins in the subnetwork created in step 2.
  4. Complete upstream pathway that connects the enriched transcription factors to kinases through known protein-protein interactions via the Expression2Kinases (X2K) algorithm.

API

The LINCS Joint Project Case Study

In a recent study published in Nature Communications, Niepel et al. (2017) combined L1000 expression signatures together with cell growth phenotypes for over 600 drug-cell line combinations utilizing over hundred drugs, many of them kinase inhibitors. The case study provides the up and down differentially expressed genes after drug perturbations by these kinase inhibitors. Using the X2K pipeline it is possible to recover the targeted kinase as a highly ranked entry within the last KEA step.

Batch Perturbation Drug Dose, μM Time, hrs Cell Line Up/Down
Batch Perturbation Drug Dose, μM Time, hrs Cell Line

Command line tools

You can download command line standalone versions of the X2K tools in JAR format.
Command near each download link suggests usage:

X2K with source code (61.3 MB) java -jar X2K.jar genelist output.xml

X2K only binary (28.9 MB) java -jar X2K.jar genelist output.xml

ChEA (8.1 MB) java -jar ChEA.jar [background] genelist output.csv

G2N (3.6 MB) java -jar G2N.jar input output.sig [backgroundSigFiles...]

KEA (188 KB) java -jar KEA.jar [background] genelist output.csv

L2N (2 MB) java -jar L2N.jar gene_list [background_file...] output.xml

Download datasets

Kinome Regulation
Database Download Type Interactions Unique Kinases Unique Substrates PMID
ARCHS4 CSVGMTSIG Co-expression 9936 517 3824
BIND CSVGMTSIG Literature PPI 2533 227 1323
Harmonizome CSVSIGGMT ML Predictions 10000 79 3635
HPRD CSVGMTSIG Literature PPI 5043 262 2159
huMAP CSVGMTSIG Mass-Spec PPI 1385 156 955
iPTMnet CSVGMTGMT Literature K-S 947 131 724
iREF CSVSIGGMT Literature PPI 26734 329 8036
KEA_2018 CSVSIGGMT Literature PPI 30521 514 7946
KEGG CSVGMTSIG Literature PPI 2238 131 621
MINT CSVGMTSIG Literature PPI 1583 225 1065
NetworkIN CSVSIGGMT Predictions 5829 190 2006
Phospho.ELM CSVGMTSIG Literature K-S 1441 231 891
Phosphopoint CSVSIGGMT Literature K-S 1970 281 1061
PhosphositePlus CSVGMTSIG Literature K-S 6434 168 2680
Protein-Protein Interactions
Database Download Type Interactions Interactors PMID
BIND SIG Literature PPI 25622 5528
Biocarta SIG Literature PPI 756 352
BioGRID SIG Mixed 68759 7312
BioPLEX SIG Mass-spec 56553 8610
DIP SIG Literature PPI 3822 1946
figeys SIG Mass-spec 6452 2033
HPRD SIG Literature PPI 47496 7490
huMAP SIG Mass-spec 62214 6061
InnateDB SIG Literature PPI 4576 1523
IntAct SIG Mixed 15726 4186
iREF SIG Mixed 28417 5403
KEGG SIG Literature PPI 13993 1198
MINT SIG Literature PPI 75065 9415
MiPS SIG Mass-spec 606 373
PDZbase SIG Literature PPI 244 159
PPID SIG Literature PPI 6998 1208
Sets2Networks SIG Predicted 3000 828
SNAVI SIG Literature PPI 2007 442
Stelzl SIG Mass-spec 6207 1702
Vidal SIG Yeast-2-Hybrid 6726 2541
Transcriptional Regulation
Database Download Type Interactions [M/H] TFs [M/H] Interactors [M/H] PMID
ARCHS4 GMTGMT Co-expression 518466 / 472585 1734 / 1724 21857 / 21918
ChEA_2016 GMTGMT ChIP-seq 535545 / 461570 194 / 178 34462 / 35204
CREEDS GMTGMT LOF-Microarray 6140050 / 3583008 265 / 174 23170 / 20592
ENCODE_2015 GMTGMT ChIP-seq 259695 / 1218728 44 / 175 18170 / 22008
Enrichr_Co-occurence GMT Co-occurrence 516300 1721 12487
huMAP GMT Mass-spec 0 / 14017 0 / 419 0 / 2109
iREF GMTGMT Mixed 7239 / 57042 402 / 1372 3454 / 11021
JASPAR-TRANSFAC GMTGMT PWM 139520 / 424314 104 / 222 20895 / 22258
TF-PPIs_Genes2Fans GMT Predictions 22525 278 6001
TF-LOF_Expression_GEO GMTGMT LOF-Microarray 86951 / 85829 82 / 43 23876 / 23585