A computer-implemented method for inferring activity of a JAK-STAT3 cellular signaling pathway in a subject performed by a digital processing device, wherein the inferring comprises: receiving expression levels of three or more target genes of the JAK-STAT3 cellular signaling pathway measured in a sample of the subject, determining an activity level of a JAK-STAT3 transcription factor (TF) element in the sample of the subject, the JAK-STAT3 TF element controlling transcription of the three or more JAK-STAT3 target genes, the determining being based on evaluating a calibrated mathematical pathway model relating the expression levels of the three or more JAK-STAT3 target genes to the activity level of the JAK-STAT3 TF element, and inferring the activity of the JAK-STAT3 cellular signaling pathway in the subject based on the determined activity level of the JAK-STAT3 TF element in the sample of the subject, wherein the three or more JAK-STAT3 target genes are selected from the group consisting of: BCL2L1, BIRC5, CCND1, CD274, FOS, HIF1A, HSP90AA1, HSP90AB1, MMP1, and MYC, or from the group consisting of: BCL2L1, CD274, FOS, HSP90B1, HSPA1B, ICAM1, IFNG, JunB, PTGS2, STAT1, TNFRSF1B, and ZEB1, and wherein the three or more JAK-STAT3 target genes selected from the group consisting of: BCL2L1, BIRC5, CCND1, CD274, FOS, HIF1A, HSP90AA1, HSP90AB1, MMP1, and MYC, are used to differentiate between epithelial tumor samples, of which the activity of the JAK-STAT3 cellular signaling pathway is active vs. inactive, or wherein the three or more JAK-STAT3 target genes selected from the group consisting of: BCL2L1, CD274, FOS, HSP90B1, HSPA1B, ICAM1, IFNG, JunB, PTGS2, STAT1, TNFRSF1B, and ZEB1, are used to differentiate between hematological samples of which the activity of the JAK-STAT3 cellular signaling pathway is active vs. inactive. receiving expression levels of three or more target genes of the JAK-STAT3 cellular signaling pathway measured in a sample of the subject, determining an activity level of a JAK-STAT3 transcription factor (TF) element in the sample of the subject, the JAK-STAT3 TF element controlling transcription of the three or more JAK-STAT3 target genes, the determining being based on evaluating a calibrated mathematical pathway model relating the expression levels of the three or more JAK-STAT3 target genes to the activity level of the JAK-STAT3 TF element, and inferring the activity of the JAK-STAT3 cellular signaling pathway in the subject based on the determined activity level of the JAK-STAT3 TF element in the sample of the subject, wherein the three or more JAK-STAT3 target genes are selected from the group consisting of: BCL2L1, BIRC5, CCND1, CD274, FOS, HIF1A, HSP90AA1, HSP90AB1, MMP1, and MYC, or from the group consisting of: BCL2L1, CD274, FOS, HSP90B1, HSPA1B, ICAM1, IFNG, JunB, PTGS2, STAT1, TNFRSF1B, and ZEB1, and wherein the three or more JAK-STAT3 target genes selected from the group consisting of: BCL2L1, BIRC5, CCND1, CD274, FOS, HIF1A, HSP90AA1, HSP90AB1, MMP1, and MYC, are used to differentiate between epithelial tumor samples, of which the activity of the JAK-STAT3 cellular signaling pathway is active vs. inactive, or wherein the three or more JAK-STAT3 target genes selected from the group consisting of: BCL2L1, CD274, FOS, HSP90B1, HSPA1B, ICAM1, IFNG, JunB, PTGS2, STAT1, TNFRSF1B, and ZEB1, are used to differentiate between hematological samples of which the activity of the JAK-STAT3 cellular signaling pathway is active vs. inactive. <EOS>