Systems and methods for analyzing persistent homeostatic perturbations

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.

1 . A method for detecting a stress response in a subject comprising detecting an altered level of a biomarker in a sample from a subject, as compared to the level of a biomarker in a corresponding sample from a subject that has a baseline stress response, thereby detecting a stress response in the subject. 
     
     
         2 . The method of  claim 1 , wherein the subject is an animal, a plant, a microorganism, or a combination thereof. 
     
     
         3 . The method of  claim 2 , wherein the animal is a vertebrate or invertebrate. 
     
     
         4 . The method of  claim 2 , wherein the animal is a mammal, fish, amphibian, reptile or bird. 
     
     
         5 . The method of  claim 4 , wherein the mammal is a human, dolphin, whale, elephant, dog, cat, cow, sheep, pig, horse, donkey, mule, or goat. 
     
     
         6 . The method of  claim 2 , wherein the microorganism is a protist, a fungus, an algae or a bacterium. 
     
     
         7 . The method of  claim 1 , wherein the sample material is solid, fluid or gaseous. 
     
     
         8 . The method of  claim 1 , wherein the sample material is selected from the group containing breath air, saliva, urine, sweat, tears, blood, serum, stool, phlegm, bone marrow, cerebrospinal fluid, seminal fluid, vaginal fluid, amniotic fluid, skin, breast milk, tissue, plant sap, an egg, microbial body, cells suspension or a combination thereof. 
     
     
         9 . The method of  claim 1 , wherein the biomarker is selected from a stress response pathway. 
     
     
         10 . The method of  claim 9 , where in the stress response pathway is selected from the group consisting of oxidative stress response, cellular detoxification and xenobiotics removal, protein chaperoning and exosome production, cell growth and energy metabolism, cell death and autophagy, cell adhesion and cytoskeleton stress, neuroendocrine signaling, innate and specific immunity, deoxyribonucleic acid repair and modification, microbial activation, neuroendocrine signaling, osmotic stress response, and a combination thereof. 
     
     
         11 . The method of  claim 1 , wherein the biomarker is a nucleic acid or a protein or a peptide or a small molecule. 
     
     
         12 . The method of  claim 1 , wherein the biomarker is acidic trehalase-like protein 1, adrenocorticotropic hormone, aldose reductase, aquaporin 5, ALG-2 interacting protein X, β-endorphin, caspase 8, CD63, cyclin D1, cyclooxygenase 2, cytochrome P450, cytochrome P450 reductase, cytoplasmic cytochrome c, Dicer, epidermal growth factor receptor, ferritin, glucocorticoid receptor, glucose regulated protein Grp58, glucose regulated protein Grp75, glutathione S-transferase π, heat shock protein 25/27, heat shock protein 40, heat shock protein 60, heat shock protein 70, heat shock protein 90, heat shock transcription factor HSF-1, heme oxygenase-1, hyperosmotic glycerol response 1, interleukin IL-1B, interleukin IL-6, interleukin IL-8, interleukin IL-10, interleukin IL-12, laminin, leptin receptor, metallothionein, stress-activated MAP kinase Mekk-1, mitogen-activated MAP kinase Mek-1, Mucin 1, NADPH-cytochrome P450 reductase, natriuretic peptide receptor A, neuropathy target esterase, inducible nitric oxide synthase II, nuclear factor of activated T cells 5, osmotic stress protein 94, Oxytocin receptor, proto-oncogene c-Fos protein, proto-oncogene c-Jun protein, salivary agglutinin gp340, serotonin receptor, serotonin, sodium/myo-inositol cotransporter, substance P, superoxide dismutase Mn, superoxide dismutase Cu/Zn, taurine transporter, tetherin, toll-like receptor 2, transforming growth factor β, trehalase, tumor suppressor p53, vascular endothelia growth factor and vasoactive intestinal peptide, and a combination thereof. 
     
     
         13 . The method of  claim 1 , wherein the level of at least two biomarkers is determined. 
     
     
         14 . The method of  claim 13 , wherein the at least two biomarkers are heat shock factor-1, ferritin, superoxide dismutase Cu/Zn, Mekk-1, and/or superoxide dismutase Mn. 
     
     
         15 . The method of  claim 1 , wherein the detection of an altered stress response is further correlated with at least one of: i) the presence, absence, or severity of a particular disease state; or ii) the likelihood that the organism will contract or be subject to a particular disease state. 
     
     
         16 . The method of  claim 15 , wherein the disease state is selected from the group consisting of dehydration, toxic chemical poisoning, radiochemical poisoning, inflammation, brain seizures, cancer, T-cell leukemia, heart lesions, stroke, neurodegenerative disease, tissue trauma, immunological deficiency, viral infection, Alzheimer's disease, vascular dementia, autoimmune disease, gastric ulcer, chronic pain, oral diseases associated with decreased salivation, obesity, metabolic syndrome, diabetes, rapid weight loss, intestinal and blood lipid abnormalities, HIV, AIDS, HTLV infection, skin disorders, cystic fibrosis, nasal allergy, protozoan infection, fatigue, anemia, alcohol abuse, infectious diseases, cardiovascular disease, multiple sclerosis, amyotrophic lateral sclerosis, irritable bowel syndrome, depression, panic disorders, post-traumatic stress disorder, neurocognitive disorder due to traumatic brain injury (NCDT), and reproductive disorders. 
     
     
         17 . A method of characterizing a stress response in a subject comprising analyzing the activity or expression of a biomarker in a sample from the subject, thereby characterizing a stress response of the subject. 
     
     
         18 . The method of  claim 17 , wherein one or more biomarkers are analyzed. 
     
     
         19 . The method of  claim 17 , wherein the biomarker is selected from a stress response pathway. 
     
     
         20 . The method of  claim 19 , wherein the stress response pathway is selected from the group consisting of redox, xenobiotics, chaperoning and exosomes, cell growth, cell death and autophagy, adhesion and cytoskeleton stress, neuroendocrine signaling, immunity, deoxyribonucleic acid repair and modification, microbial activation and stress responses, oxidative stress, osmotic stress, cellular detoxification, and cell cycle and energy metabolism and a combination thereof. 
     
     
         21 - 73 . (canceled)