Workflow indicates the data acquisition and relations between the methods.

Enrichment heatmap of Hallmark gene sets in each TC associated with patient OS. GSEA results of 14 TCs associated with OS in univariate or multivariate survival analysis are presented, including Hallmark gene sets that were included in the enrichment for at least one TC that passed the Bonferroni threshold for multiple testing correction. The gene sets were clustered using Pearson correlation and Ward D2, and the heatmap colors were based on Z-scores, truncated at a value of four. The right column shows the chromosomal location of a copy number alteration that the TC captures the downstream effects on gene expression levels.

Survival tree analysis of patients with platinum-treated HGSOC defines survival cohorts with distinct clinicopathologic and biological characteristics. Survival tree analysis of 294 patients with platinum-treated HGSOC using 14 OS-associated TCs and other classifiers such as age, tumor stage, grade, and debulking status. The analysis resulted in nine survival cohorts, and the height of the bar in the Sankey diagram represents the number of patients in each cohort. The Kaplan-Meier plots and number-at-risk tables are presented with survival data censored at 10 years. The names of the survival cohorts were based on enriched biological processes in the TCs, as determined by the chromosomal location of genes captured by a TC, GSEA, and co-functionality analysis of the top genes. The p-values in each panel show the p-value from the corresponding log-rank test between the two groups. Abbreviations: TC = transcriptional component, ECM = extracellular matrix.

Co-functionality network of top 100 absolute weighted genes in TC121. One cluster with more than 5 genes was identified in both Gene ontology biological processes and cellular components databases having strong shared predicted co-functionality (r1>10.7). This cluster shows high enrichment for genes related to the synaptic signaling in the Gene ontology biological processes database and synaptic membrane in the cellular components database.

The activity of TC121 in bulk transcriptomes of CCLE, GDSC cell lines, and GEO and TCGA patient-derived samples. A. Cross-study TC projection of TC121 on CCLE and GDSC cell lines. The boxplots display the activity scores of TC121 in different tissue types, which are ordered based on their corresponding median activity scores. B. Cross-study TC projection of TC121 on GEO and TCGA bulk transcriptomes resulted in the activity scores presented in the boxplots. Cancer types were ordered based on corresponding medians of TC121 activity scores. Abbreviations: TC = transcriptional component.

Spatial transcriptomic profiles in ovarian cancer samples. A. We employed a permutation-based approach to pinpoint the areas of significant TC activity in spatial transcriptomic profiles. We ran 5,000 permutations for each TC-profile combination, yielding a p-value that indicates the extent to which the TC activity in the corresponding profile differs from what would be expected by chance (the null distribution). We then transformed these p-values into logarithmic values and represented them using a heatmap. Heatmaps of activity scores of the TCs are presented in individual rows for the HGSOC, serous papillary, and endometrioid adenocarcinoma of ovary samples. The first column represents the stained images of the samples. The second to seventh columns show heatmaps corresponding to the mentioned TCs. B. The heatmap illustrates the colocalization between two TC activities on spatial transcriptomic profiles from ovarian cancer samples. For each cell, the colocalization scores of the TCs at each of the three spatial transcriptomics samples OC 1, OC 2, and OC 3 are arranged in columns. A colocalization score of 4 between two TCs (red) indicates that the positively (+) and negatively (-) active regions of both TCs are perfectly colocalized. Conversely, a colocalization score of -4 between two TCs (blue) also indicates colocalization. Still, with inverse activity, i.e., the positively active regions of one TC are colocalized with the negatively active regions of the other TC or vice versa. A colocalization score close to 0 between two TCs (white) indicates that the activities of two TCs are spatially separated. The dashed and solid circle in the panel on the right side of the color bar represents two different TCs. Abbreviations: TC = transcriptional component.