Medical prognosis and prediction of treatment response using multiple cellular signaling pathway activities

A technology of cell signaling and pathways, applied in informatics, bioinformatics, medical informatics, etc.

Pending Publication Date: 2018-05-22
KONINKLJIJKE PHILIPS NV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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  • Medical prognosis and prediction of treatment response using multiple cellular signaling pathway activities
  • Medical prognosis and prediction of treatment response using multiple cellular signaling pathway activities
  • Medical prognosis and prediction of treatment response using multiple cellular signaling pathway activities

Examples

Experimental program
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Embodiment 1

[0197] Example 1: Inferring the activity of two or more cell signaling pathways

[0198] As detailed in the published international patent application WO 2013 / 011479 A2 (“Assessment of cellular signaling pathway activity using probabilistic modeling of target gene expression”), by constructing a probabilistic model, for example, a Bayesian model, and introducing many different target genes The conditional probabilistic relationship between the expression level of β and the activity of the cell signaling pathway, this model can be used to determine the activity of the cell signaling pathway with high precision. Furthermore, probabilistic models can be easily upgraded to incorporate additional knowledge gained through late-stage clinical studies by adjusting conditional probabilities and / or adding new nodes to the model to represent additional sources of information. In this way, the probabilistic model can be appropriately updated to include recent medical knowledge.

[0199] ...

Embodiment 2

[0374] Example 2: Determining Risk Score

[0375] In general, a number of different formulas can be devised for determining the risk of a combination indicating that a subject will experience a clinical event within a defined time period and based on the inferred activity of two or more cell signaling pathways in the subject Rating, namely:

[0376] MPS = F ( P i ) + X ,in i = 1... N , (3)

[0377] in MPS Denotes a risk score (the term " MPS ” is used herein as an abbreviation for “multi-pathway score” in order to indicate that the risk score is influenced by the putative activity of two or more cell signaling pathways), P i Indicates cell signaling pathways i activity, N represents the total number of cell signaling pathways used to calculate the risk score, and X are placeholders for possible further factors and / or parameters that may enter into the equation. Such formulas may more specifically be polynomials of some degree in a given variable, or linear ...

Embodiment 3

[0427] Example 3: CDS Application

[0428] refer to Figure 19 (Diagram showing a clinical decision support (CDS) system configured to determine a risk score indicative of a subject's risk of experiencing a clinical event within a defined time period, as disclosed herein), with the clinical decision support (CDS) system 10 as suitably configured The computer 12 realizes. Computer 12 may be configured to operate CDS system 10 by executing suitable software, firmware, or other instructions stored on a non-transitory storage medium (not shown), such as a hard drive or other magnetic storage medium , an optical disc or another optical disc storage medium, a random access memory (RAM), a read only memory (ROM), a flash memory, or another electronic storage medium, a network server, and the like. Although the illustrative CDS system 10 is embodied by an illustrative computer 12, more generally, a CDS system may be embodied by a digital processing device or an instrument containing...

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Abstract

The present application mainly relates to specific method for determining a risk score that indicates a risk that a subject will experience a clinical event within a defined period of time. The risk score is determined based on a combination of inferred activities of two or more cellular signaling pathways in a subject, wherein the cellular signaling pathways comprise a TGF-beta pathway and one ormore of a PI3K pathway, a Wnt pathway, an ER pathway, and an HH pathway. The present application also relates to an apparatus, to a non-transitory storage medium, and to a computer program for determining a risk score that indicates a risk that a subject will experience a clinical event within a defined period of time. The present invention also relates to a kit for measuring expression levels ofthree or more target genes of each of two or more cellular signaling pathways in a sample of a subject, to kits for determining a risk score that indicates a risk that a subject will experience a clinical event associated with a disease within a defined period of time, and to uses of the kits in performing the method.

Description

field of invention [0001] The topics described herein relate primarily to bioinformatics, the field of genome processing, the field of proteome processing, and related fields. More specifically, the present invention relates to a computer-implemented system for determining a risk score indicative of a subject's risk of experiencing a disease-related clinical event within a defined period of time, the determination being performed by a digital processing device, wherein the A risk score is determined from a combination of the inferred activities of two or more cell signaling pathways in a patient. The present invention further relates to a device (comprising a digital processor configured to perform the method) for determining a risk score indicating that a subject will experience a risk of a disease-related clinical event within a defined period of time, for determining A non-transitory storage medium (which stores instructions executable by a digital processing device to per...

Claims

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Application Information

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IPC IPC(8): G06F19/12G06F19/18C12Q1/68G16B5/20G16B20/20G16B20/30
CPCC12Q1/6809G16B20/00G16H50/30G16H50/20G16B25/10C12Q1/6886C12Q2600/158G16B20/30G16B20/20G16B5/20C12Q2537/165G16B5/00C12Q2600/16
Inventor H.J.范奥詹A.G.C.范布鲁斯塞J.维罗贝D.A.M.W.范斯特里普R.范戈格
Owner KONINKLJIJKE PHILIPS NV
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