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

A cell signal and pathway technology, applied in informatics, bioinformatics, medical informatics, etc.

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

AI Technical Summary

Problems solved by technology

However, interpreting these complex data to extract relevant clinical information has proven challenging and remains largely unsolved

Method used

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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
Comparison scheme
Effect test

Embodiment 1

[0148] Example 1: Inferring the activity of two or more cell signaling pathways

[0149] 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.

[0150] ...

Embodiment 2

[0271] Example 2: Determining Risk Score

[0272] In general, a number of different formulas can be devised for determining a risk score indicative of the risk that a subject will experience a clinical event within a defined time period and based on a combination of inferred activities of two or more cell signaling pathways in the subject, namely:

[0273] MPS = F ( P i ) + X ,in i = 1... N , (3)

[0274] 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 l...

Embodiment 3

[0316] Example 3: CDS application

[0317] refer to Figure 11 (Graphically showing a clinical decision support (CDS) system configured to determine a risk score indicating the risk that a subject will experience a clinical event within a determined time period, as disclosed herein), the clinical decision support (CDS) system 10 as a suitably configured computer 12 realized. 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 disk or another optical storage medium, random access memory (RAM), read only memory (ROM), flash memory, or another electronic storage medium, a network server, or the like. Although the illustrative CDS system 10 is embodied by the illustrative computer 12, more generally, the CDS system may be embodied by a digital processing device or instrument comprising a digit...

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PUM

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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 PI3K pathway and one or more of 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 of three 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 the fields of bioinformatics, genome processing, proteome processing, and related fields. More particularly, the present invention relates to a computer-implemented method for determining a risk score indicating a risk that a subject will experience a disease-related clinical event within a determined time period, the method being performed by a digital processing device, wherein the subject is based on two A risk score is determined by combining the putative activity of one or more cell signaling pathways. The present invention further relates to an apparatus (comprising a digital processor configured to perform the method) for determining a risk score indicating a risk that a subject will experience a disease-related clinical event within a determined time period, for determining a risk score indicating that the subject will experience a disease-related clinical event A non-transitory storage medium o...

Claims

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Application Information

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IPC IPC(8): C12Q1/68G06F19/00G06F19/12G06F19/18G06F19/22G16B5/20G16B20/20G16B20/30G16B30/00G16H50/20G16H50/30
CPCC12Q2600/112C12Q2600/118G16B20/00G16H50/30G16H50/20G16B25/10C12Q1/6883C12Q1/6886C12Q2600/158C12Q2600/16G16B20/30G16B20/20G16B30/00G16B5/20G16B5/00
Inventor H.J.范奥詹W.F.J.维哈伊格A.G.C.范布鲁斯塞J.维罗贝R.范戈格
Owner KONINKLJIJKE PHILIPS NV
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