Determination of jak-stat1/2 pathway activity using unique combination of target genes

A computer program product for determining the activity level of a JAK-STAT1/2 cellular signaling pathway in a subject comprising:

• a. a non-transitory computer readable storage medium having computer readable program code embodied therewith, the computer readable program code executable by at least one processor to:
• i. calculate an activity level of a JAK-STAT1/2 transcription factor element in a sample isolated from a subject, wherein the activity level of the JAK-STAT1/2 transcription factor element in the sample is associated with JAK-STAT1/2 cellular signaling, and wherein the activity level of the JAK-STAT1/2 transcription factor element in the sample is calculated by:
• 1. receiving data on the expression levels of at least three target genes derived from the sample, wherein the at least three target genes are selected from BID, GNAZ, IRF1, IRF7, IRF8, IRF9, LGALS1, NCF4, NFAM1, OAS1, PDCD1, RAB36, RBX1, RFPL3, SAMM50, SMARCB1, SSTR3, ST13, STAT1, TRMT1, UFD1L, USP18, and ZNRF3;
• 2. calculating the activity level of the JAK-STAT1/2 transcription factor element in the sample using a calibrated pathway model, wherein the calibrated pathway model compares the expression levels of the at least three target genes in the sample with expression levels of the at least three target genes in the calibrated pathway model which define an activity level of the JAK-STAT1/2 transcription factor element;
• and,
• ii. calculate the activity level of the JAK-STAT1/2 cellular signaling pathway in the sample based on the calculated activity level of the JAK-STAT1/2 transcription factor element in the sample,
• wherein the activity level of the JAK-STAT1/2 cellular signaling pathway is determined to be either IFN type I activity or IFN type II activity by using two calibrated pathway models of which one is calibrated on IFN type I activity and the other is calibrated on IFN type II activity.

A method of treating a subject suffering from a disease associated with an activated JAK-STAT1/2 cellular signaling pathway comprising:

• a. receiving information regarding the activity level of a JAK-STAT1/2 cellular signaling pathway derived from a sample isolated from the subject, wherein the activity level of the JAK-STAT1/2 cellular signaling pathway is determined by:
• i. calculating an activity level of a JAK-STAT1/2 transcription factor element in a sample isolated from the subject, wherein the activity level of the JAK-STAT1/2 transcription factor element in the sample is associated with JAK-STAT1/2 cellular signaling, and wherein the activity level of the JAK-STAT1/2 transcription factor element in the sample is calculated by:
• 1. receiving data on the expression levels of at least three target genes derived from the sample, wherein the JAK-STAT1/2 transcription factor element controls transcription of the at least three target genes, and wherein the at least three target genes are selected from BID, GNAZ, IRF1, IRF7, IRF8, IRF9, LGALS1, NCF4, NFAM1, OAS1, PDCD1, RAB36, RBX1, RFPL3, SAMM50, SMARCB1, SSTR3, ST13, STAT1, TRMT1, UFD1L, USP18, and ZNRF3;
• 2. calculating the activity level of the JAK-STAT1/2 transcription factor element in the sample using a calibrated pathway model, wherein the calibrated pathway model compares the expression levels of the at least three target genes in the sample with expression levels of the at least three target genes in the calibrated pathway model which define an activity level of JAK-STAT1/2 transcription factor element;
• and,
• ii. calculating the activity level of the JAK-STAT1/2 cellular signaling pathway in the sample based on the calculated activity level of the JAK-STAT1/2 transcription factor element in the sample;
• and,
• b. administering to the subject a JAK-STAT1/2 inhibitor if the information regarding the activity level of the JAK-STAT1/2 cellular signaling pathway is indicative of an active JAK-STAT1/2 cellular signaling pathway,
• wherein the activity level of the JAK-STAT1/2 cellular signaling pathway is determined to be either IFN type I activity or IFN type II activity by using two calibrated pathway models of which one is calibrated on IFN type I activity and the other is calibrated on IFN type II activity.

A kit for measuring expression levels of JAK-STAT1/2 cellular signaling pathway target genes comprising:

• a. a set of polymerase chain reaction primers directed to at least six JAK-STAT1/2 cellular signaling pathway target genes derived from a sample isolated from a subject;
• and
• b. a set of probes directed to the at least six JAK-STAT1/2 cellular signaling pathway target genes;
• wherein the at least six target genes are selected from BID, GNAZ, IRF1, IRF7, IRF8, IRF9, LGALS1, NCF4, NFAM1, OAS1, PDCD1, RAB36, RBX1, RFPL3, SAMM50, SMARCB1, SSTR3, ST13, STAT1, TRMT1, UFD1L, USP18, and ZNRF3.

A kit for determining the activity level of a JAK-STAT1/2 cellular signaling pathway in a subject comprising:

• a. one or more components capable of identifying expression levels of at least three JAK-STAT1/2 cellular signaling pathway target genes derived from a sample of the subject, wherein the at least three target genes are selected from BID, GNAZ, IRF1, IRF7, IRF8, IRF9, LGALS1, NCF4, NFAM1, OAS1, PDCD1, RAB36, RBX1, RFPL3, SAMM50, SMARCB1, SSTR3, ST13, STAT1, TRMT1, UFD1L, USP18, and ZNRF3;
• and,
• b. optionally, a non-transitory computer readable storage medium having computer readable program code embodied therewith, the computer readable program code executable by at least one processor to:
• i. calculate an activity level of a JAK-STAT1/2 transcription factor element in the sample, wherein the activity level of the JAK-STAT1/2 transcription factor element in the sample is associated with JAK-STAT1/2 cellular signaling, and wherein the activity level of the JAK-STAT1/2 transcription factor element in the sample is calculated by:
• 1. receiving data on the expression levels of the at least three target genes derived from the sample;
• 2. calculating the activity level of the JAK-STAT1/2 transcription factor element in the sample using a calibrated pathway model, wherein the calibrated pathway model compares the expression levels of the at least three target genes in the sample with expression levels of the at least three target genes in the calibrated pathway model which define an activity level of the JAK-STAT1/2 transcription factor element;
• and,
• ii. calculate the activity level of the JAK-STAT1/2 cellular signaling pathway in the sample based on the calculated activity level of the JAK-STAT1/2 transcription factor element in the sample,
• wherein the activity level of the JAK-STAT1/2 cellular signaling pathway is determined to be either IFN type I activity or IFN type II activity by using two calibrated pathway models of which one is calibrated on IFN type I activity and the other is calibrated on IFN type II activity.