A computer-implemented method for inferring activity of a Notch cellular signaling pathway in a subject performed by a digital processing device, wherein the inferring comprises: receiving expression levels of five or more target genes of the Notch cellular signaling pathway measured in a sample of the subject, determining an activity level of a Notch transcription factor element in the sample of the subject, the Notch TF element controlling transcription of the five or more Notch target genes, the determining being based on evaluating a calibrated mathematical pathway model relating the expression levels of the five or more Notch target genes to the activity level of the Notch TF element, and inferring the activity of the Notch cellular signaling pathway in the subject based on the determined activity level of the Notch TF element in the sample of the subject, wherein the five or more Notch target genes are selected from the group consisting of: DTX1, EPHB3, HES1, HES4, HES5, HEY2, MYC, NFKB2, NRARP, PIN1, PLXND1, and SOX9, wherein two or more Notch target genes are selected from the group consisting of: DTX1, HES1, HES4, HES5, HEY2, MYC, and NRARP, and three or more Notch target genes are selected from the group consisting of: EPHB3, NFKB2, PIN1, PLXND1, and SOX9, wherein the method is used in at least one of the following activities: diagnosis based on the inferred activity of the Notch cellular signaling pathway in the subject; prognosis based on the inferred activity of the Notch cellular signaling pathway in the subject; and wherein the subject is suffering from, or suspected to be suffering from, a brain cancer. receiving expression levels of five or more target genes of the Notch cellular signaling pathway measured in a sample of the subject, determining an activity level of a Notch transcription factor element in the sample of the subject, the Notch TF element controlling transcription of the five or more Notch target genes, the determining being based on evaluating a calibrated mathematical pathway model relating the expression levels of the five or more Notch target genes to the activity level of the Notch TF element, and inferring the activity of the Notch cellular signaling pathway in the subject based on the determined activity level of the Notch TF element in the sample of the subject, wherein the five or more Notch target genes are selected from the group consisting of: DTX1, EPHB3, HES1, HES4, HES5, HEY2, MYC, NFKB2, NRARP, PIN1, PLXND1, and SOX9, wherein two or more Notch target genes are selected from the group consisting of: DTX1, HES1, HES4, HES5, HEY2, MYC, and NRARP, and three or more Notch target genes are selected from the group consisting of: EPHB3, NFKB2, PIN1, PLXND1, and SOX9, wherein the method is used in at least one of the following activities: diagnosis based on the inferred activity of the Notch cellular signaling pathway in the subject; prognosis based on the inferred activity of the Notch cellular signaling pathway in the subject; and wherein the subject is suffering from, or suspected to be suffering from, a brain cancer. diagnosis based on the inferred activity of the Notch cellular signaling pathway in the subject; prognosis based on the inferred activity of the Notch cellular signaling pathway in the subject; and wherein the subject is suffering from, or suspected to be suffering from, a brain cancer.