Additional file 1 of TOP2A and CENPF are synergistic master regulators activated in cervical cancer

Additional file 1: Supplementary Table 1: MR DA and DE signatures for the 10 datasets. “MR_set”, categories of functions of MRs (TF, transcriptional factor; TFcoFac, transcriptional co-factors; SigPathway, signal pathway); “regulon_size”, number of regulons for a MR; “rank_cat”, category of ranking. For example, 100 indicates that the MR is a common MR of the top 100 activated MRs in the 5 discovery datasets. -100 indicates that the MR is a common MR of the top 100 suppressed MRs in the 5 discovery datasets. 0 indicates the MR is not the common top MRs in the 5 discovery datasets. “nes.”, the NES score of a MR in a dataset calculated using VIPER, representing the DA signature. “pval.”, the P-value of the NES from the VIPER analysis. “t.”, the value representing the DE signature (e.g. the t-statistics for microarray). “DiscoverySet_DA-DE_consistent”, whether the DA and DE are consistent. The DA-DE Consistency set was selected using |DE| value> 3 and same sign as DA in all the five discovery datasets. Supplementary Table 2: DE signatures of the common regulons of TOP2A and CENPF for the 10 datasets. “MOR_sign”, sign of MOR (positive (1) or negative (− 1) MOR for both TOP2A-regulons and CENPF-regulons). “DE.average”, the average values of the DE values for the 10 datasets. Supplementary Table 3: Network of TOP2A, CENPF and their regulons. “Regulator” is the gene ID of a MR (here CENPF or TOP2A). “interaction” is always “regulate”. “Target” is the regulon of a regulator. “MOR”, mode of regulation, ranges between − 1 and + 1. “likelihood”, range from 0 to 1, an edge weight that indicates how strong the mutual information for an edge is. All information was extracted from the aracne.networks R package. Supplementary Table 4: “Functional Annotation Clustering” analysis of the 34 TOP2A-CENPF common regulons on DAVID 6.8 website. See DAVID website for details of methods used and interpretation of header names. “Category”, the gene annotation category. UP_KEYWORDS, UniProt Keywords annotation of genes; UP_SEQ_FEATURE, UniProt sequence feature annotation of genes; GOTERM_BP_DIRECT, Gene ontology biological process annotation; GOTERM_CC_DIRECT, Gene ontology cellular component annotation. Supplementary Table 5: CENPF and TOP2A expression in dataset Biewenga_2008 (GSE7410). The expression data were extracted from GEO database using GEO2R tool. The probe ID is indicated after the gene symbol. “Avg_Gex”, the average expression value of CENPF and TOP2A. “sample_type”, sample type (N, healthy cervical tissue; C, Early stage cervical tumour without lymph node metastasis; M, Early stage cervical tumour with lymph node metastasis). Supplementary Table 6: CENPF, TOP2A expression and clinical, molecular data in CC samples in TCGA. The clinical and molecular feature information were from the supplementary Table 1 and 2 of the publication: The Cancer Genome Atlas Research Network et al., 2017. The expression values of CENPF and TOP2A were downloaded from TSVdb. Supplementary Table 7: Somatic mutations associated with expression of CENPF and TOP2A in CC TCGA data. Each row is an association of a gene (Gene.mutation) with missense or LOF mutations and expression of CENPF or TOP2A tested using Wilcoxon Rank-Sum test. “delta. Median.Exp” is the difference of average expression of samples with mutation and samples without mutation. “Direction.Exp” indicates whether the samples with mutation has higher or lower expression than the samples without mutation. P-value is indicated in “Wilcox.P” column. Only associations with a P < 0.1 were included in the list. Supplementary Table 8: DAVID “Functional Annotation Clustering” analysis of the genes with mutations associated with high or low expression of TOP2A or CENPF. See DAVID website for details of methods used and interpretation of header names. “Category”, the gene annotation category. UP_KEYWORDS, UniProt Keywords annotation of genes; KEGG_PATHWAY, KEGG pathway annotation of genes. Supplementary Table 9: Connections of expression signature of TOP2A, CENPF and their common regulons with all expression signatures in Connectivity Map (CMap) using the QUERY app of CLUE. Each row is a perturbation in CMap. Id, perturbation ID; type, type of perturbation (CP, compound; KD, gene knockdown; OE, gene over-expression; PCL, perturbation class); HA1E, PC3, VCAP, A375, A549, HCC515, HT29, MCF7, HEPG2, the connectivity score for the indicated cell lines; summary, summary connectivity score of all cell lines; Average_CancerCells, average connectivity score of 8 cancer cell lines (except for HA1E (human kidney epithelial cell), all other cell lines are cancer cell lines). Name, perturbation name; Description, perturbation description; Target, the target of a compound; “belongs_to”, the PCL the perturbation belongs to. The table was sorted based on ascending Average_CancerCells. The top rows represent perturbations thar reverse (downregulate) the expression of Top2A, CENPF and their common regulons. The negative connectivity scores from − 95 to − 100 were formatted in Excel in blue background with increasing darkness.