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Systems and methods for analyzing persistent homeostatic perturbations

Inactive Publication Date: 2009-05-07
SOUTHERN SARKA O
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0020]In one embodiment, the measured levels of SR biomarkers are converted into a normalized and log-transformed SR biomarker score for more convenient data processing.

Problems solved by technology

Stress has been linked to the risk and severity of health disorders and diseases.
Stress also has adverse effects on reproduction, on the aging process and on longevity.
These hormones are not suitable targets for a general analysis of stress, because they are not relevant to many types of stressors.
Moreover, these individual stress biomarkers alone cannot discriminate between stress and responses to short-term hardships, such as school exams or exercise.
Furthermore, these hormone-based stress tests are not useful to analyze the molecular mechanism of stress because these two biomarkers are only related to two SR pathways; the limbic hypothalamic-pituitary-adrenal axis (glucorticoids) and the sympathetic nervous system (catecholamines.)
Indeed, many types of stressors do not activate these pathways.
Moreover, these two stress tests have very limited applications in veterinary care, wildlife conservation and ecology, because they are not suitable for most nonhuman species.

Method used

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  • Systems and methods for analyzing persistent homeostatic perturbations
  • Systems and methods for analyzing persistent homeostatic perturbations
  • Systems and methods for analyzing persistent homeostatic perturbations

Examples

Experimental program
Comparison scheme
Effect test

example 1

Construction of a SR Biomarker Panel

[0237]This experiment provides an exemplary method for constructing a SR biomarker panel that is useful for a broad-based analysis of persistent homeostatic perturbations (i.e., “stress”). Although as described below, expression levels of SR biomarker proteins are exemplified, the same assay principles could easily be adapted to a nucleic acid-based assay to measure, for example, mRNA encoding these proteins, which one would expect to be up-regulated when the associated SR pathways were activated.

[0238]Candidate SR biomarkers. Approximately 2000 articles related to stressor effects on humans, animals, plants and microorganisms were compiled from peer-reviewed scientific literature. Meta-analysis of the articles was used to select candidate biomarkers based on two criteria:

[0239](1) Association with one or more universal SR pathways.

[0240](2) Expression in multiple species of animals. Preferred candidate biomarkers were expressed in all taxonomic g...

example 2

Construction of a Minimized SR Biomarker Panel

[0254]In this Example, the 40 SR biomarker panel described in Example 1 was used to construct and validate a minimized panel of 5 SR biomarkers that was capable of classifying the reference samples with the same reliability as the 40 SR biomarker panel.

[0255]Selection of SR Biomarkers Based on High Score Variability. The variability of SR biomarker scores in reference samples from control versus stressed subjects was determined using principal component analysis. The first two principal components, pc1 and pc2, cumulatively accounted for >97% of the variability. The variability index was calculated as:

vi=l1ix1i+l2ix2i

where;

vi is the variability index for the i-th SR biomarker (i−1, . . . , 40);

l1i and l2i are the pc1 and pc2 eigenvalues for the i-th SR biomarker; and

x1i and x2i are the absolute values of pc1 and pc2 eigenvectors for the i-th SR biomarker.

[0256]The variability index, vi for the 40 SR biomarkers is in Table 4 below.

TABLE ...

example 3

SR Pathway Profiles for Analyzing Molecular Mechanisms of Stress

[0258]In addition to the SR biomarker profiles described above in Examples 1 and 2, SR pathway profiles can also be constructed to more particularly analyze the molecular mechanisms of stress in differentially activating individual SR pathways.

[0259]SR Pathway Profile Construction. To determine the molecular mechanism of stress, “pathway activation analysis” was performed. The principle of this analysis is the conversion of a SR biomarker profile into a “SR pathway profile” (FIG. 1.) SR pathway profiles are useful as indicators of the molecular mechanism of stress by revealing which SR pathways are most activated and which SR pathways have a coordinated regulation. SR pathway profiles can also be used for classifying samples as being from normal versus stressed subjects in the same manner as SR biomarker profiles.

[0260]SR pathway profiles were calculated using the following formula:

Z=[Z1⋮Z10]≈Z1=f1,1y1+f1,2y2+…+f1,40y40...

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Abstract

This invention is in the field of homeostasis analysis. More particularly, it relates to systems and methods for analyzing persistent homeostatic perturbations, i.e. chronic stress, by measuring levels of biomarkers that are related to chronic stress. This invention is also directed to systems and methods for analyzing the molecular mechanisms of chronic stress.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]This application is a Continuation-in-Part of U.S. patent application Ser. No. 12 / 282,840, filed Sep. 12, 2008, which is a 35 USC § 371 National Stage application of International Application No. PCT / US2008 / 004448 filed Apr. 4, 2008, now pending; which claims the benefit under 35 USC § 119(e) to U.S. Application Ser. No. 60 / 910,158 filed Apr. 4, 2007, now abandoned. The disclosure of each of the prior applications is considered part of and is incorporated by reference in the disclosure of this application.FIELD OF THE INVENTION[0002]The present invention relates generally to systems and methods for analyzing persistent homeostatic perturbations and more specifically to measuring levels of biomarkers that are related to chronic stress.BACKGROUND OF THE INVENTION[0003]The health of living organisms is maintained through a self-regulatory process called homeostasis. Limited, short-term perturbations of homeostasis caused by routine hardships...

Claims

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Application Information

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IPC IPC(8): G01N33/53C12Q1/02C12Q1/34C12Q1/26G06F7/00C12Q1/30C12Q1/48G01N33/566
CPCG01N33/6893G01N2800/60G01N2500/10G01N2800/00A61K45/00G01N33/68G01N2800/7004
Inventor SOUTHERN, SARKA O.
Owner SOUTHERN SARKA O
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