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Dynamic network biomarker detection device detection method and detection program

Foreign code F170008992
File No. EF001P03WO
Posted date Mar 14, 2017
Country Republic of Korea
Application number 20157010816
Gazette No. 20150079641
Gazette No. 102111820
Date of filing Feb 12, 2013
Gazette Date Jul 8, 2015
Gazette Date May 15, 2020
International application number JP2013053188
International publication number WO2014050160
Date of international filing Feb 12, 2013
Date of international publication Apr 3, 2014
Priority data
  • P2012-211921 (Sep 26, 2012) JP
  • 2013JP53188 (Feb 12, 2013) WO
Title Dynamic network biomarker detection device detection method and detection program
Abstract The present invention provides a device, method, and program for detection of a biomarker candidate that may be used in a diagnosis of a pre-disease state indicating a transition from a healthy state to a disease state. Biological samples are collected from a subject to be measured at different times. Statistical data is obtained by aggregating measurement data obtained in measurement on collected biological samples. Thereafter, a process of obtaining high-throughput data (s1), a process of choosing differential biological molecules (s2), a process of clustering (s3), a process of choosing a DNB candidate (s4), and a process of identifying a DNB by significance analysis (s5) are carried out.
(From US2015278433 A1)
Outline of related art and contending technology BACKGROUND ART
According to various studies, many disease, disease progression of the deterioration of particularly complex processes, climate systems, ecological systems, economic system or the like in a manner similar to the system, beyond the threshold point is above some threshold, called a branch point is reached, the state transitions occur kaaaaa, the health status of the disease state is changed from the top (e.g., see non Patent Literature 1-5). These complex dynamic mechanisms of the disease in the study, exacerbation of the disease (e.g., an asthma attack, the onset of cancer) progression of processes, dependent on the time and modeled as a nonlinear dynamic system, which is modeled by observing the system, the phase transition at the branching point to deteriorate rapidly bottle has already been found that a (see non patent document 1, 6).
Fig. 1 is a diagram conceptually showing the progression of the disease according to the present processes. Fig. 1 a shows the progression of the disease is schematically indicated by the processes. Fig. 1 B of a, C and d in the course of the progression of processes, the above potential stability of the system is modeled as a function, and the abscissa represents elapsed time and the, potential function for the value of the longitudinal axis of the graph is conceptually shown. As shown in Fig. 1 a of thus, the progress of the exacerbation of the disease processes, the steady state (state of health), disease state, disease state can be represented as. In the normal state, the system is stable, Fig. 1 B of the position of a black circle as shown as a, is a minimum value of the potential function are in. In the disease state, the system is, in Fig. 1 C of the black circle as shown as the location of, the value of the potential function may be too high. Thus, the influence of disturbance is liable to be affected by a state, only a small disturbance is affected by the phase transition temperature to a vicinity of the branching point, i.e., position and the steady state limit. However, before the disease state, by appropriate treatment, easily be restored to the normal state. On the other hand, in the disease state, the system is stable, the position of the black circle of Fig. 1 D as indicated as a, the value of the minimum of the potential function providing unit are in. Therefore, the phase transition from a normal condition is caused by the disease state, before returning to a steady state is difficult.
Thus, if the contents prior to detect the state of a disease, disease state before the transition, the transition to the state of the disease and the patient may be used if the advance notice, by taking appropriate measures, to a normal state from the patient before the disease can be returned to the high likelihood.
That is, a branch point (critical threshold) if it can detect, by prediction of a critical transition, early diagnosis of disease can be realized.
In addition, conventionally as a method for diagnosing a disease state, when the biomarker is utilized. Conventionally used and would be a common biomarker, a biometric sample from the serum, urine and the like of body fluid, in addition, included in the tissue at a molecular level DNA, RNA, proteins, metabolites and the like, in vivo biological change can be grasped quantitatively an indication. Biomarkers for diagnosis of diseases by conventional methods, normal samples (samples taken from the state of health) extracted from one or more biomarker samples (samples taken in a disease state) from the user by comparing the biomarker, a method of diagnosing.
Scope of claims [claim1]
1. In vivo measurement obtained by the plurality of printing items based on the measurement data, a living body to be measured before transitioning from a normal condition of the disease state in the state prior to the detecting device detects as a disease, wherein each factor of each of items of measurement data based on the correlation between time series change in the plurality of printing items classified into a plurality of clusters and a distribution means, each factor of each cluster classified with respect to the item and each of the measurement data the measurement data of the time series of change in a time sequence of changes between a first cluster based on the correlations between a predetermined appearance condition suitable to the selection in the case, in the state prior to occurrence of the disease with the device being suitable as a biomarker comprising judging means and the detection device.

[claim2]
2. Method according to claim 1, wherein measurement data of the item factors, and has changed with the lapse of significance whether the calibrated differential further comprises a calibration means, said determining means for printing the item, wherein the changes with time by means of differential assay is an assay that significance factors with the signal from said item of apparatus.

[claim3]
3. Method according to claim 2, the differential calibration means, the measurement data of a previously set item factor is based on a result of comparison with reference data, performing an assay of significance of the detection device.

[claim4]
4. Method according to claim 1, the factor items, items of the measurement for a gene, protein measurement items, measurement items relating to a metabolism, and in vivo image obtained from a measurement item comprises at least one of the detection device.

[claim5]
5. Method according to claim 1, the judgment means based on the biomarker dynamic network, an indication of an error regarding the presence or absence of said living body, from living to a normal state before transitioning the state of the disease state of a glucose disease, and wherein the biometric is at least one of a likelihood of having the disease occidental determination supporting information comprises output means for outputting said detection device.

[claim6]
6. Determining the state of a living body as a decision support method, comprising a first detection device 1 is determined based on the biomarker dynamic network, from a living body is in a steady state before transitioning the state of the disease condition decision support that supports determination of a state before the method.

[claim7]
7. In vivo measurement obtained by measuring the plurality of printing items based on the data, from a living body to be measured in a normal state before transitioning the state of the disease condition in the state prior to detection using a detection method, wherein each factor of each of items of measurement data based on the correlation between a change in a time sequence of the plurality of printing items to a plurality of clusters classified by the classifying step, classifying each factor of each cluster with respect to the item between the time series of each of the measurement data and measurement data between clusters in a time sequence of changes representing the correlation between a change in predetermined selection conditions based on the appearance of a case adapted for, in the state prior to the appearance of the suitable dynamic network condition determination step is executed as a biomarker that is detected.

[claim8]
8. Method according to claim 7, wherein measurement data of the item factors, and has changed with the lapse of significance whether or not to perform the step of assaying and differential assay, wherein the item is in the determination step factor, the change over time by the differential assay step that the significance factors is calibrated to the item detection method.

[claim9]
9. Method according to claim 8, the differential assay step, the at least one item factor set beforehand measured data based on the result of comparison with reference data, to perform an assay of significance of said detection method.

[claim10]
10. Method according to claim 7, the factor items, measurement items relating to the gene, protein measurement items, measurement items relating to a metabolism, and in vivo image obtained from a measurement item comprises at least one of said detection method.

[claim11]
11. Method according to claim 7, wherein the determining step is determined based on the biomarker dynamic network, an indication of the presence or absence of an error regarding the in vivo, wherein the living body to a normal state before transitioning the state of the disease from the disease state before desmethoxy, with the possibility of a living body and at least one disease occidental determination step of outputting the information supporting the execution of the method.

[claim12]
12. Computer, relating to a living organism obtained by the measurement based on the measured data of the plurality of printing items to, from a living body to be measured in a normal state before transitioning the state of the disease condition to execute the processing for detecting a state before the detection program is recorded in a computer readable recording medium, the computer, wherein each factor of each of items of measurement data based on the correlation between a change in a time sequence of the plurality of printing items to a plurality of clusters classified by the classifying step, classifying each factor of each cluster with respect to the item between the time series of change between each of the measurement data and measurement data of the cluster based on the correlation between time series change of a predetermined appearance condition suitable for the selection in the case of, in the state prior to the appearance of the suitable dynamic network condition determination step as a biomarker to execute the computer readable recording medium.

[claim13]
13. Method according to claim 12, computer, said print item of measurement data, and has changed with the lapse of significance whether to perform the step of assaying and differential assay, wherein the factors in the determination step item, by differential assay step that the changes with time significance factors is calibrated to the item computer readable recording medium.

[claim14]
14. Method according to claim 13, as differential assay step, the measurement data of a previously set item factor is based on a result of comparison with reference data, to perform an assay of the significance of the computer readable recording medium.

[claim15]
15. Method according to claim 12, the factor items, items of the measurement for a gene, protein measurement items, measurement items relating to a metabolism, and in vivo image obtained from a measurement item comprises at least one of the computer readable recording medium.

[claim16]
16. Method according to claim 12, wherein in the determining step determining the biomarker based on the dynamic network, an indication of an error regarding the presence or absence of said living body, from living to a normal state before transitioning the state of the disease state of a glucose disease, having a living body and at least one of the likelihood of disease occidental determination step of outputting the information supporting the executed computer readable recording medium.
  • Applicant
  • JAPAN SCIENCE AND TECHNOLOGY AGENCY
  • Inventor
  • AIHARA, Kazuyuki
  • CHEN, Luonan
  • LIU, Rui
  • LIU, Zhiping
  • LI, Meiyi
IPC(International Patent Classification)
Reference ( R and D project ) FIRST Mathematical Theory for Modeling Complex Systems and its Transdisciplinary Applications in Science and Technology AREA
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