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JP-7857338-B2 - Methods and systems for linking chemical emissions with corresponding genetic, medical, and/or pathological conditions.

JP7857338B2JP 7857338 B2JP7857338 B2JP 7857338B2JP-7857338-B2

Inventors

  • ハーシュティック，ハレル
  • モリス，ドリュー
  • カントール，エフド

Assignees

  • セント メディカル テクノロジーズ リミテッド

Dates

Publication Date
20260512
Application Date
20240521
Priority Date
20181104

Claims (20)

  1. A method for associating volatile organic compound (VOC) release with at least one target cell type before and after treatment in a selected population, comprising the following steps: For each selected target cell type, a procedure (212) to determine the gene sequence of at least one of the target cell samples (202) obtained from multiple patients; A procedure (212) for determining the gene sequence of at least one healthy cell sample of healthy cells collected (204) from the plurality of patients with respect to each of the selected target cell types, wherein the healthy cell sample is of the same cell type as the target cell sample; A procedure (212) for determining the gene sequence of at least one control cell sample of control cells taken from a control group (206) with respect to each selected target cell type, wherein the control cell sample is of the same cell type as the target cell sample; A procedure (212) for classifying each of the at least one gene sequences according to molecular classification; A procedure (216) for culturing the target cell sample, the healthy cell sample, and the control cell sample to produce target cell cultures, healthy cell cultures, and control cell cultures, respectively; A procedure (218) for obtaining VOC release data for the target cell culture, the healthy cell culture, and the control cell culture before inducing mass cell death (MCD); A procedure (220) for generating filtered VOC release data from pre-MCD target cell cultures and filtered VOC release data from healthy pre-MCD cell cultures with respect to at least one gene sequence of each of the molecular classifications; Procedure (220) for generating filtered VOC release data from pre-MCD control cell cultures; A procedure for inducing MCD in the target cell culture, the healthy cell culture, and the control cell culture (222); Procedure for obtaining VOC release data from target cell cultures after MCD, VOC release data from healthy cell cultures after MCD, and VOC release data from control cell cultures after MCD (224); A procedure (226) for generating filtered post-MCD target cell culture VOC release data and filtered post-MCD healthy cell culture VOC release data with respect to at least one gene sequence of each of the molecular classifications; Procedure for generating filtered VOC release data from post-MCD control cell cultures (226); A procedure (228) for determining the VOC profile of pre-MCD target cells and post-MCD target cells from the filtered VOC release data of pre-MCD target cell cultures and the filtered VOC release data of post-MCD target cell cultures; Procedure (230) for determining the pre-MCD healthy cell VOC profile and the post-MCD healthy cell VOC profile from the filtered pre-MCD healthy cell culture VOC release data and the filtered post-MCD healthy cell culture VOC release data; A procedure (231) for determining the pre-MCD control cell VOC profile and the post-MCD control cell VOC profile from the filtered pre-MCD control cell culture VOC release data and the filtered post-MCD control cell culture VOC release data; A procedure (232) for determining the predicted target cell VOC profile, the predicted healthy cell VOC profile, and the predicted control cell VOC profile for each of the aforementioned molecular classifications, with respect to at least one gene sequence; Procedure (214) for obtaining VOC emission data of VOCs released from at least one sample of respiration and at least one body fluid collected from a control group (208); A procedure (234) for generating a dynamic control cell VOC profile from the predicted control cell VOC profile and the VOC release data of the VOC released in at least one sample of the control group; A procedure (210) for obtaining VOC emission data of VOCs released from at least one sample of respiration and at least one body fluid collected (200) from multiple patients (200) in the selected population with respect to each of the selected target cell types ; Procedure (236) for generating a dynamic differential VOC profile, wherein the dynamic differential VOC profile is generated with respect to each of the at least one gene sequences of the molecular classification from the predicted target cell VOC profile, the predicted healthy cell VOC profile, and the VOC emission data of the at least one sample; A procedure (238) for comparing the dynamic differential VOC profile with the dynamic control cell VOC profile; and a procedure (240) for saving the dynamic differential VOC profile and the dynamic control cell VOC profile in a database. A method that includes this.
  2. The molecular classification is the method according to claim 1, wherein each of the at least one gene sequences is classified as a gene mutation according to the cancer type.
  3. The method according to claim 1, wherein the procedure for generating the filtered pre-MCD target cell culture VOC release data, the filtered pre-MCD healthy cell culture VOC release data, and the filtered pre-MCD control cell culture VOC release data reduces the influence of irrelevant VOC artifacts, thereby better identifying VOCs associated with the at least one gene sequence before the procedure for inducing the MCD.
  4. The procedure for generating the filtered VOC release data from pre-MCD target cell cultures, the filtered VOC release data from healthy pre-MCD cell cultures, and the filtered VOC release data from control pre-MCD cell cultures is as follows: A procedure for comparing the VOC release data of the target cell culture with both the filtered VOC release data of healthy cell cultures before MCD and the filtered VOC release data of control cell cultures before MCD; A procedure for comparing the VOC release data of healthy cell cultures with both the filtered VOC release data of pre-target cell cultures and the filtered VOC release data of pre-control cell cultures; A procedure for comparing the VOC release data of the control cell culture with the filtered VOC release data of the pre-MCD healthy cell culture. The method according to claim 1, including the method described in claim 1.
  5. The method according to claim 1, wherein the procedure for inducing the MCD includes a method that does not generate VOC artifacts.
  6. The method according to claim 5 , wherein the method is selected from the group consisting of rapid freezing technology and UV light technology.
  7. The method according to claim 1, wherein the VOC release data related to the target cell culture, the healthy cell culture, and the control cell culture, as well as the post-MCD target cell culture VOC release data, the post-MCD healthy cell culture VOC release data, and the post-MCD control cell culture VOC release data, are derived from the same target cell culture, healthy cell culture, and control cell culture.
  8. The method according to claim 1, wherein the procedure for generating the filtered post-MCD target cell culture VOC release data , the filtered post-MCD healthy cell culture VOC release data, and the filtered post-MCD control cell culture VOC release data reduces the influence of irrelevant VOC artifacts and thereby better identifies VOCs associated with the at least one gene sequence after the procedure for introducing the MCD.
  9. The procedure for producing the filtered post-MCD target cell culture VOC release data, the filtered post-MCD healthy cell culture VOC release data, and the filtered post-MCD control cell culture VOC release data is as follows: A procedure for comparing the VOC release data of the target cell culture with both the VOC release data of healthy cell cultures after MCD and the VOC release data of control cell cultures after MCD; The method according to claim 1, comprising the steps of: comparing the VOC release data of healthy cell cultures with both the VOC release data of target cell cultures after MCD and the VOC release data of control cell cultures after MCD; and comparing the VOC release data of control cell cultures with the VOC release data of healthy cell cultures after MCD.
  10. The procedure for determining the predicted target cell VOC profile, the predicted healthy cell VOC profile, and the predicted control cell VOC profile is as follows: A procedure for predicting the VOC concentration level in at least one sample from the VOC profiles of pre-MCD target cells and post-MCD target cells; A procedure for predicting the VOC concentration level in at least one sample from the VOC profiles of healthy cells before MCD and healthy cells after MCD; and a procedure for predicting the VOC concentration level in at least one sample from the VOC profiles of control cells before MCD and control cells after MCD. The method according to claim 1, including the method described in claim 1.
  11. The method according to claim 10 , wherein the VOC concentration level is predicted by using a diffusion model.
  12. The method according to claim 11 , wherein the diffusion model is selected from the group consisting of Farhi's equation and a modified Farhi model.
  13. The method according to claim 1, wherein the procedure for generating the dynamic control cell VOC profile includes a step of minimizing the error between the predicted control cell VOC profile and the VOC emission data in at least one sample of the control group.
  14. The method according to claim 1, further comprising the step of associating the VOC emission data with at least one known medical condition.
  15. The method according to claim 14 , further comprising a step of comparing VOC emission data before and after treatment of the aforementioned medical condition.
  16. A method for associating volatile organic compound (VOC) emissions with selected cancers in a selected population, comprising the following steps: A procedure (162) to determine the gene sequence of at least one of the target cell samples (152) of target cells collected from multiple patients of a selected cancer type in the aforementioned selected population; A procedure (162) for determining the gene sequence of at least one healthy cell sample of healthy cells collected (154) from the aforementioned multiple patients, wherein the healthy cell sample is of the same cell type as the target cell sample; A procedure (162) for determining the gene sequence of at least one control cell sample of control cells collected (156) from a control group, wherein the control cell sample is of the same cell type as the target cell sample; A procedure (162) for classifying each of the at least one gene sequences based on at least one gene mutation of the selected cancer type; A procedure (166) for culturing one of the target cell sample, the healthy cell sample, and the control cell sample to produce a target cell culture, a healthy cell culture, and a control cell culture, respectively; Procedure for obtaining VOC release data for the target cell culture, the healthy cell culture, and the control cell culture (168); A procedure (170) for generating a target cell VOC profile, a healthy cell VOC profile, and a control cell VOC profile, respectively, from the target cell culture VOC release data, the healthy cell culture VOC release data, and the control cell culture VOC release data, for each of the at least one gene mutations; A procedure (164) for obtaining VOC emission data of VOCs released from respiration and at least one sample of at least one body fluid collected from a control group (158) ; A procedure (172) for determining the predicted target cell VOC profile, the predicted healthy cell VOC profile, and the predicted control cell VOC profile for each of the at least one gene mutations of the selected cancer type by predicting the VOC concentration level in the at least one sample obtained from the target cell VOC profile, the healthy cell VOC profile, and the control cell VOC profile, respectively; A procedure (176) for generating a dynamic control cell VOC profile from the predicted control cell VOC profile and the VOC release data of the VOC released in at least one sample of the control group; A procedure (174) for generating a dynamic differential VOC profile for each of the at least one gene mutations of the selected cancer type from the predicted target cell VOC profile, the predicted healthy cell VOC profile, and the VOC release data of the at least one sample; A procedure (178) for comparing the dynamic differential VOC profile with the dynamic control cell VOC profile; and a procedure (180) for saving the dynamic differential VOC profile and the dynamic control cell VOC profile to a database. A method that includes this.
  17. A procedure for filtering VOC release data from the target cell culture; The method according to claim 16 , further comprising a step of filtering the VOC release data of the healthy cell culture; and a step of filtering the VOC release data of the control cell culture.
  18. The filtering procedure described above is further divided into the following sub-procedures: A procedure for comparing the VOC release data of the target cell culture with both the VOC release data of the healthy cell culture and the VOC release data of the control cell culture; A procedure for comparing the VOC release data of the healthy cell culture with both the VOC release data of the target cell culture and the VOC release data of the control cell culture; The method according to claim 17 , comprising the step of comparing the VOC release data of the control cell culture with the VOC release data of the healthy cell culture.
  19. The procedure for generating the target cell VOC profile, the healthy cell VOC profile, and the control cell VOC profile is as follows: A procedure for comparing the filtered target cell culture VOC release data with both the filtered healthy cell culture VOC release data and the filtered control cell culture VOC release data; The method according to claim 17, comprising the steps of: comparing the filtered healthy cell culture VOC release data with both the filtered target cell culture VOC release data and the filtered control cell culture VOC release data; and comparing the filtered control cell culture VOC release data with the filtered healthy cell culture VOC release data.
  20. The method according to claim 16 , wherein the VOC concentration level is predicted by using a diffusion model.

Description

The disclosed technologies relate, in general, to identifying chemical releases in the human body and/or cultures, and more specifically to methods and systems for correlating chemical releases in the human body and/or cultures with corresponding genetic, medical, and/or pathological conditions. Background of the Disclosed Technology: Metabolic, anabolic, and/or catabolic processes produce chemical compounds. Some of these compounds belong to three groups: volatile organic compounds (VOCs), semi-volatile organic compounds (SVOCs), and volatile sulfur-containing compounds (VSCs). Compounds in these groups typically remain in a gaseous state at room temperature. Monitoring gases associated with metabolic, anabolic, and/or catabolic processes is well known in the art. For example, monitoring oxygen ( O₂ ) saturation levels is used to monitor a patient's condition. Similarly, carbon dioxide ( CO₂ ) is used as an indicator in a wide range of lung-related diseases. The publication, "Summary of Safety and Probable Benefit, Menssana Research, Inc. Hearts Breath Test for Grade 3 Heart Transplant Rejection," focuses on monitoring respiratory VOCs in heart transplant recipients to support the diagnosis of Grade 3 heart transplant rejection. The publication "A Review of the Volatiles From the Healthy Human Body" by de Lacy Costello et al. covers a list of VOCs reported from the bodies of healthy humans. In this list, a total of 1840 VOCs were identified in respiration, saliva, urine, milk, blood, skin secretions, and feces. 872 were found in respiration, 359 in saliva, 154 in blood, 256 in milk, 532 in skin secretions, 279 in urine, and 381 in feces. The publication to Ulanowská et al., "The Application of Statistical Methods Using VOCs to Identify Patients with Lung Cancer," focuses on an attempt to classify lung cancer biomarkers. For this purpose, respiratory samples were obtained from 137 patients with confirmed lung cancer. These samples were analyzed using SPME-GC/MS. Exhaled breath samples were also obtained as a reference group from 143 healthy volunteers with different smoking habits (active smokers, passive smokers, and non-smokers). Statistical methods such as discriminant analysis (DA) and the CHAID tree model were used for data processing and evaluation. Ulanowska suggested that chemotherapy for lung cancer can be controlled by utilizing molecular biomarkers such as amino acids, peptides, lipids, and carbohydrates, and that these may be defined as molecules reflecting the pathological state of the organ and characteristic pharmacological responses to therapeutic interventions. In 2012, Altomare described that respiratory analysis using triple quadrupole gas chromatography-mass spectrometry (hereinafter referred to as "GC-MS/MS") can detect characteristic VOCs in specific disease conditions such as colorectal cancer and melanoma. PCT patent application WO2014/180974 to Domingues Ortega, titled "VOC-Based, Narcolepsy Diagnostic Method," relates to the detection of narcolepsy in a patient by obtaining a sample from a subject and detecting the level of at least one VOC in the sample to obtain a VOC profile of the sample. The VOC profile of the sample is then compared to a reference VOC profile to determine whether the patient has narcolepsy. This is a schematic example of a system constructed and effective by embodiments of the disclosed technology for associating the elimination of chemical substances in at least one of human respiration, bodily fluids, and cell cultures with corresponding expressions of genetic or medical conditions, for utilizing these associations for diagnosis, and/or for determining the effectiveness of treatment, and/or for determining the choice of treatment.This is a schematic example of VOC emission data from another embodiment of the disclosed technology.This is a schematic example of a differential VOC profile according to another embodiment of the disclosed technology.This is a schematic example of an exemplary method for associating VOC releases with corresponding cancer types in a selected population, which will be effective through further embodiments of the disclosed technology.This is a schematic example of an exemplary method for associating VOC releases with corresponding cancer types in a selected population, which will be effective through further embodiments of the disclosed technology.This is a schematic example of an exemplary method for associating VOC releases with corresponding cancer types in a selected population, which will be effective through further embodiments of the disclosed technology.This is a schematic example of a method for associating VOC release with target cells before and after treatment in a selected population, which is effective by another embodiment of the disclosed technology.This is a schematic example of a method for associating VOC release with target cells before and after treatment in a selected population, which is effective by another e