Assessment of cellular signaling pathway activity using probabilistic modeling of target gene expression

A method comprising:

• inferring activity of one or more cellular signaling pathway(s) in tissue of a medical subject based at least on the expression level(s) (20) of one or more target gene(s) of the cellular signaling pathway(s) measured in an extracted sample of the tissue of the medical subject, wherein the inferring comprises:
• inferring activity of the cellular signaling pathway(s) in the tissue of the medical subject by evaluating at least a portion of a probabilistic model (40-1, . . . , 40-7), preferably a Bayesian network (40-1, . . . , 40-7), representing the cellular signaling pathway(s) for a set of inputs including at least the expression level(s) (20) of the one or more target genes of the cellular signaling pathway(s) measured in the extracted sample of the tissue of the medical subject;
• estimating a level (46) in the tissue of the medical subject of at least one transcription factor (TF) element, the at least one TF element controlling transcription of the one or more target gene(s) of the cellular signaling pathway(s), the estimating being based at least in part on conditional probabilities relating the at least one TF element and the expression level(s) (20) of the one or more target gene(s) of the cellular signaling pathway(s) measured in the extracted sample of the tissue of the medical subject;
• inferring activity of the cellular signaling pathway(s) based on the estimated level in the tissue sample of the transcription factor;
• and
• determining whether the cellular signaling pathway(s) is/are operating abnormally in the tissue of the medical subject based on the inferred activity of the cellular signaling pathway(s) in the tissue of the medical subject;
• wherein the inferring is performed by a digital processing device (12) using the probabilistic model (40-1, . . . , 40-7) of the cellular signaling pathway(s).