Method for processing biological information and apparatus for processing biological information

Abstract

To acquire information on the activation and inhibition of expression of a living body state of a loving body.SOLUTION: A living body information processing method comprises: acquiring respective differences between a chromatin structure and a living body state of a living body at a first time point and the chromatin structure and the living body state of the living body at a second time point after the first time point; identifying, on the basis of the respective differences in the chromatin structure and the living body state of the living body, a histone modification that causes a change in the chromatin structure altering the living body state; acquiring correspondence information indicating correspondence between the identified histone modification and the living body state of the living body corresponding to the histone modification; and identifying, on the basis of the correspondence information, a histone modification for activating or suppressing expression of a designated living body state in a target living body which is of the same species as said living body.SELECTED DRAWING: Figure 1

Description

Technical Field

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[0001] The present invention relates to a biological information processing method and a biological information processing apparatus.

Background Art

[0002] Epigenetics is a mechanism by which changes in gene expression or phenotype are inherited from a cell or multicellular organism to its offspring without changes in the DNA sequence. The mechanisms of epigenetics are thought to involve chemical modifications of DNA such as DNA methylation, chemical modifications of histones, and changes in the structure or stability of nucleosomes or chromatin due to these modifications.

[0003] Patent Document 1 discloses a method of extracting information regarding the history of epigenetic modifications of a living body, analyzing the similarity of the extracted information with other living bodies, and predicting and controlling changes in the state of a future living body.

Prior Art Documents

Patent Documents

[0004]

Patent Document 1

Summary of the Invention

[0008] The biological information processing device according to the present invention comprises a storage unit that stores correspondence information indicating the correspondence between histone modifications of a living organism and the biological state of the living organism corresponding to said histone modifications, and a calculation unit that, when designated information for activating or suppressing the expression of a biological state is input to a target living organism of the same species as said living organism, estimates the histone modifications for activating or suppressing the expression of said biological state based on the correspondence information stored in the storage unit, wherein in the correspondence information, the histone modifications that cause changes in chromatin structure that change the biological state are identified based on the differences between the chromatin structure and biological state of the living organism at a first time point and the chromatin structure and biological state at a second time point after the first time point. [Effects of the Invention]

[0009] According to the present invention, it is possible to obtain information regarding the activation and suppression of the expression of biological states in living organisms. [Brief explanation of the drawing]

[0010] [Figure 1] Figure 1 is a flowchart showing the flow of the biometric information processing method according to this embodiment. [Figure 2] Figure 2 is a schematic diagram illustrating the principles of epigenetics. [Figure 3] Figure 3 shows an example of a neural network. [Figure 4] Figure 4 is a functional block diagram showing an example of a biological information processing device according to this embodiment. [Modes for carrying out the invention]

[0011] Hereinafter, embodiments of the biological information processing method and biological information processing apparatus according to the present invention will be described with reference to the drawings. However, the present invention is not limited by these embodiments. Furthermore, the components in the following embodiments include those that are easily substituted or substantially identical to those that are easily substituted by those skilled in the art.

[0012] Figure 1 is a flowchart showing the flow of the biological information processing method according to this embodiment. As shown in Figure 1, the biological information processing method according to this embodiment includes a difference detection step (S10), a first histone modification identification step (S20), a correspondence information calculation step (S30), a biological state specification step (S40), and a second histone modification identification step (S50).

[0013] First, the principle of the bioinformation processing method according to this embodiment will be explained. The bioinformation processing method according to this embodiment is based on a mechanism called epigenetics. Epigenetics is a mechanism by which changes in gene expression or phenotype are inherited from cells or multicellular organisms to their offspring without changes in the DNA sequence.

[0014] Figure 2 schematically illustrates the principle of epigenetics. It shows a chromatin structure in which DNA is wrapped around proteins called histones. The chromatin structure changes when histones are modified by methylation, ubiquitination, phosphorylation, acetylation, etc. Changes in the chromatin structure alter the activation and suppression of gene expression that affects the biological state.

[0015] For example, methylation of histones suppresses the expression of biological states by genes. Histones are formed in a string-like (tail-like) structure consisting of, for example, 20 to 30 amino acids. The amino acids that make up histones are targets for various modifications. As shown in Figure 2, modification of the histone H3 tail and histone H4 tail by methylation (Me) and acetylation (Ac) alters the activation and suppression of biological state expression by genes. Specifically, methylation of the amino acids indicated by K4, K36, and K79 in the histone H3 tail activates transcription, which copies genetic information from DNA to mRNA. Conversely, methylation of the amino acids indicated by K9 and K27 in the histone H3 tail and the amino acid indicated by K20 in the histone H4 tail suppresses transcription.

[0016] Thus, changes in histone modifications can activate or suppress the expression of biological states by genes.

[0017] The inventors have found that changes in chromatin structure may be caused by, for example, certain factors. Examples of such factors include environmental factors based on the environment in which the organism lives, such as latitude, longitude, and climate; experiential factors based on the experiences the organism gains through its life; psychological factors based on the organism's psychological stress and sense of well-being; age factors based on the organism's age; and sex factors based on the organism's sex.

[0018] For example, organisms that have lived for extended periods in high-temperature environments at low latitudes are known to possess a high capacity for sweating. In other words, in this case, it can be considered that the chromatin structure of the organism has changed in such a way that prolonged exposure to high temperatures activates the expression of sweating capacity through genes.

[0019] Also, for example, in the case of humans, the brains of infants are still developing, and large-scale and complex brain tissues such as those in adult brains have not yet been formed. In the human brain, long-term memories obtained by around the age of about 3 years after birth are unstable memories created by an immature brain and are lost as they age. And old cells are not replaced by new cells; rather, the brain grows by adding new cells to existing brain cells. This indicates that old memories are not erased by neurogenesis, but as new cells are added, memories are reorganized in the brain and access to old memories becomes impossible. That is, in the case of humans, it can be considered that as the brain grows after about 3 years after birth, the chromatin structure has changed so that memories of old cells in the brain cannot be accessed.

[0020] In the above example, for instance, when a living body with low sweating ability lives in a high-temperature environment, if its sweating ability can be enhanced, it can adapt to the high-temperature environment. Also, in the human brain, memories in old cells before reorganization may retain abilities such as instinctive behaviors and the ability to sense geomagnetism. If such abilities can be utilized after growth, it may lead to new discoveries and the like. Also, apart from these examples, when there are genes that are prone to causing cancer, diabetes, autoimmune diseases, etc., it is considered useful to infer histone modifications that suppress their expression.

[0021] Therefore, in the present embodiment, the differences between the chromatin structure and the biological state of the living body at the first time point and the chromatin structure and the biological state of the living body at the second time point after the first time point are determined. Based on the respective differences in the chromatin structure and the biological state of the living body, histone modifications that cause changes in the chromatin structure that change the biological state are identified. Corresponding information indicating the correspondence between the identified histone modifications and the biological state of the living body corresponding to the histone modifications is obtained. Based on the corresponding information, histone modifications for activating or suppressing the expression in a target living body of the same species as the living body for a specified biological state are inferred.

[0022] First, in the difference detection step S10, differences between the chromatin structure and biological state of a living body at a first time point and the chromatin structure and biological state of the living body at a second time point after the first time point are detected. The chromatin structure of a living body can be obtained, for example, by collecting cells of the living body and analyzing the DNA of the collected cells by a known method. The biological information in this embodiment includes information related to the chromatin structure of a living body. Further, the biological state includes the state of the living body that changes due to changes in the chromatin structure, such as the ability of the living body or the onset of a disease. Regarding the biological state of a living body, for example, a wearable device capable of acquiring the biological state may be attached to the living body, and the biological state may be acquired from the living body at a predetermined timing. Examples of the biological state include walking speed, running speed, muscle mass, heart rate, respiratory rate, blood pressure, body temperature, brain waves, cerebral blood flow, sweating amount, presence or absence of cancer cells, and the like.

[0023] The first time point and the second time point can be arbitrary time points. When the living body is a human and is the same individual at the first time point and the second time point, the first time point may be, for example, a time point before approximately 3 years old after birth at a predetermined age, and the second time point may be a time point after approximately 3 years old after birth at the predetermined age. In this case, changes in the chromatin structure before and after the inability to access the memory of old cells in the brain at approximately 3 years old after birth at the predetermined age can be appropriately detected. Note that the living body may be an organism such as an animal or a plant other than a human.

[0024] The living body for detecting the difference in chromatin structure may be the same individual as the target living body described later, or may be an individual of a generation prior to the target living body. Conventionally, it has been considered that acquired effects due to the environment are not passed on to the next generation. For example, smoking changes the composition of lung cells and causes cancer. Such acquired effects have been considered not to be inherited across generations. That is, epigenetic memory has been considered to be completely cleared during the division of egg cells. However, in recent years, it has been proven that acquired effects may actually be inherited across generations.

[0025] Regarding how acquired influences are inherited genetically, in humans, for example, H3K27me3 is known to be associated with the suppression of gene expression that alters the chromatin structure, which is the packaging of DNA in the cell nucleus. This modification by H3K27me3 has been found to remain in the embryo after fertilization, even if other epigenetic modifications are eliminated. This indicates that the mother is passing on traces of acquired environmental influences to her offspring. Inherited epigenetic modifications are important for embryonic development. For example, it is known that embryos lacking H3K27me3 in the early stages of embryonic development, due to the removal of the trigger enzyme that alters the NA packaging of H3K27me3, are destroyed before embryonic development is complete. In other words, in reproduction, epigenetic information is not only passed from generation to generation, but is also important for the development of the embryo itself.

[0026] It has been found that several important developmental genes, which are normally turned off during early embryonic development, are turned on in embryos lacking H3K27me3. This leads to premature activation of these genes during egg cell division, disrupting embryonic development. In other words, inherited epigenetic information is necessary to process and correctly transcribe the embryonic genetic code.

[0027] These findings suggest that humans inherit more than just genes—finely tuned and crucial genetic regulatory mechanisms that can influence the environment and individual lifestyles. In other words, it provides evidence that environmental adaptations acquired during human survival are passed on to offspring through the germline. Conversely, a breakdown in these epigenetic mechanisms can lead to diseases such as cancer, diabetes, and autoimmune disorders.

[0028] In the first histone modification identification step S20, based on the differences in the chromatin structure and biological state of the organism detected in the difference detection step S10, histone modifications that cause changes in the chromatin structure that alter the biological state are identified.

[0029] In the correspondence information calculation step S30, correspondence information is obtained that shows the correspondence between the identified histone modification and the biological state of the organism corresponding to that histone modification.

[0030] Furthermore, a neural network may be pre-generated that, for example, takes the chromatin structure and biological information of a living organism at a first time point and the chromatin structure and biological information of a living organism at a second time point as input, calculates and outputs histone modifications that cause changes in the chromatin structure that alter the biological state based on the input results, and associates the output results with the biological information. Figure 3 shows an example of a neural network. The neural network NW shown in Figure 3 takes first information I1, which includes the chromatin structure and biological information of a living organism at a first time point, and second information I2, which includes the chromatin structure and biological information of a living organism at a second time point, as input, outputs third information I3, which includes the changed biological state, and fourth information I4, which includes histone modifications that cause changes in the chromatin structure that alter the biological state, and associates the third information I3 and the fourth information I4. In this case, by inputting the first information I1 and the second information I2 into the neural network NW, correspondence information can be obtained in which the third information I3 and the fourth information I4 are associated, thus enabling the difference detection step S10, the first histone modification identification step S20, and the correspondence information calculation step S30 to be performed quickly.

[0031] In the biological state specification step S40, the target biological state and information on whether to activate or suppress the expression of that biological state are specified for the target organism. The target organism is the same species as the organism in which a difference was detected in the difference detection step S10.

[0032] In the second histone modification identification step S50, based on the correspondence information calculated in the correspondence information calculation step S30, histone modifications are identified that activate or suppress the expression of the biological information specified in the biological state designation step S40 for the target organism.

[0033] Furthermore, if the organism at the first time point is from an earlier generation than the organism at the second time point, the differences between the predetermined factors of the organism at the first time point and the predetermined factors of the organism at the second time point may be determined separately from or in addition to steps S10 to S50 above. In this case, based on the differences in the chromatin structure and predetermined factors of the organism determined, predetermined factors that change the chromatin structure of the organism can be identified, and correspondence information of the previous generation showing the correspondence between the identified predetermined factors and the chromatin structure can be obtained. Then, for example, based on the correspondence information of the previous generation, the changes in the chromatin structure of the target organism can be estimated. For example, if the organism of the parent generation developed cancer at the age of 20, and there are differences in the chromatin structure between the organism at age 19 and age 20, and there are also differences in predetermined factors such as living environment and habits, and psychological factors, then the organism of the child generation can take measures to reduce the possibility of developing cancer by avoiding that living environment, habits, and psychological state.

[0034] Furthermore, for example, if the organism is a human, and the first and second time points are the same individual, and the first time point is before a predetermined age of approximately 3 years old, and the second time point is after a predetermined age of approximately 3 years old, then steps S10 to S30 above can detect changes in chromatin structure before and after a change in the biological state that occurs at approximately 3 years old, in which the organism loses the ability to access the memories of old cells in the brain. It can then identify the histone modifications that cause this change in chromatin structure and appropriately determine the correspondence information between the identified histone modifications and the biological state. In this case, if, for example, the biological state (ability) of accessing the memories of old cells in the brain is specified in biological information specification step S40, then the histone modifications corresponding to the specified biological state can be appropriately identified based on the correspondence information. Therefore, by changing the chromatin structure of the target organism based on the identified histone modifications, the biological state in which the target organism accesses the memories of old cells in the brain can be expressed and activated. Note that the predetermined age is shown as approximately 3 years old as an example, but it is not limited to this, and any age can be set.

[0035] Figure 4 is a functional block diagram showing an example of a bio-information processing device 100 according to this embodiment. As shown in Figure 4, the bio-information processing device 100 has a processing unit such as a CPU (Central Processing Unit) and a storage device such as RAM (Random Access Memory) or ROM (Read Only Memory).

[0036] The biological information processing device 100 includes an acquisition unit 10, a storage unit 20, and an arithmetic unit 30. The biological information processing device 100 may also have a communication unit (not shown). The biological information processing device 100 is connected to external devices such as an input device 40 and an output device 50. The input device 40 accepts various operations. The input device 40 is composed of various input devices such as a keyboard, mouse, buttons, switches, and a touch panel. The input device 40 can input to the biological information processing device 100, for example, a target biological state and information on whether to activate or suppress the expression of that biological state. The output device 50 is composed of a display unit and an audio output unit, etc. The output device 50 outputs the processing content of the biological information processing device 100 in the form of text, images, audio, etc. The acquisition unit 10 acquires various types of information. The acquisition unit 10 acquires information input by the input device 40, for example. The acquisition unit 10 acquires information received by a communication unit (not shown).

[0037] The memory unit 20 stores various types of information. The memory unit 20 has storage such as a hard disk drive or a solid-state drive. Alternatively, an external storage medium such as a removable disk may be used as the memory unit 20. The memory unit 20 stores various data, applications, etc., including the neural network described above and the corresponding information output by the neural network.

[0038] The arithmetic unit 30 performs various calculations. The arithmetic unit 30 performs calculations corresponding to the biological state specification step S40 and the second histone modification identification step S50. By storing the above neural network in the storage unit 20, the arithmetic unit 30 can use the neural network to perform the difference detection step S10, the first histone modification identification step S20, and the correspondence information calculation step S30. Note that the difference detection step S10, the first histone modification identification step S20, and the correspondence information calculation step S30 may be performed by a device other than the biological information processing device 100. In this case, the correspondence information obtained in advance by the other device can be stored in the storage unit 20.

[0039] As described above, the biological information processing method according to this embodiment determines the differences between the chromatin structure and biological state of the organism at a first time point and the chromatin structure and biological state of the organism at a second time point after the first time point, identifies histone modifications that cause changes in the chromatin structure that alter the biological state based on the differences in the chromatin structure and biological state of the organism, obtains correspondence information showing the correspondence between the identified histone modifications and the biological state of the organism corresponding to those histone modifications, and identifies histone modifications that activate or suppress the expression of a specified biological state in a target organism of the same species as the organism, based on the correspondence information.

[0040] Furthermore, the biological information processing device 100 according to this embodiment includes a storage unit 20 that stores correspondence information indicating the correspondence between histone modifications of a living organism and the biological state of the living organism corresponding to said histone modifications, and a calculation unit 30 that, when specified information for activating or suppressing the expression of a biological state is input to a target living organism of the same species as the living organism, identifies the histone modifications for activating or suppressing the expression of said biological state based on the correspondence information stored in the storage unit. In the correspondence information, histone modifications that cause changes in chromatin structure that change the biological state are identified based on the differences between the chromatin structure and biological state of the living organism at a first time point in time and the chromatin structure and biological state at a second time point after the first time point.

[0041] This configuration determines the differences between the chromatin structure and biological state of the organism at a first time point and at a second time point (after the first time point). Based on these differences, the histone modifications that cause changes in chromatin structure and alter the biological state are identified. This allows for highly accurate identification of histone modifications. Furthermore, based on correspondence information showing the relationship between the identified histone modifications and the biological state, histone modifications that activate or suppress the expression of the biological state in the target organism can be appropriately identified. This allows for the appropriate acquisition of information regarding the activation and suppression of the expression of the biological state in the organism. By altering the chromatin structure of the target organism based on these estimated histone modifications, the expression or suppression of a predetermined biological state can be induced in the target organism.

[0042] In the biological information processing method according to this embodiment, the organism at the first time point is an individual from an earlier generation than the organism at the second time point. The difference between a predetermined factor in the organism at the first time point and a predetermined factor in the organism at the second time point is further determined. Based on the difference between the organism's chromatin structure and the predetermined factor, a predetermined factor that changes the organism's chromatin structure is identified. Correspondence information from the previous generation showing the correspondence between the identified predetermined factor and the chromatin structure is obtained. Based on the correspondence information from the previous generation, the change in the chromatin structure of the target organism is estimated. With this configuration, histone modifications caused by predetermined factors can be identified with high accuracy. Furthermore, based on the differences obtained in individuals from earlier generations than the target organism, information regarding the activation and suppression of the expression of biological states in individuals of later generations can be appropriately obtained. In addition, by knowing the changes in histone modifications due to changes in the chromatin structure of the parent generation before the offspring are born, measures such as artificially modifying histones at a specific time can be taken in the offspring generation. Furthermore, for example, if there are differences in the chromatin structure of the parent generation's organism between the first and second time points, and also differences in certain factors, then the offspring generation's organism can take measures such as activating or suppressing the expression of specific biological information by living in a way that avoids those factors.

[0043] In the biological information processing method according to this embodiment, the biological entity is the same individual, the first time point is before a predetermined age, and the second time point is after the predetermined age. With this configuration, by correlating the differences in histone modifications of the chromatin structure that change before and after a predetermined age in the same individual, it is possible to appropriately determine the histone modifications necessary to activate the expression of the biological state obtained up to the predetermined age.

[0044] The technical scope of the present invention is not limited to the embodiments described above, and modifications can be made as appropriate without departing from the spirit of the invention. For example, in each of the embodiments described above, the difference between a predetermined factor of the organism at a first time point and a predetermined factor at a second time point after the first time point is further determined, a predetermined factor that changes the chromatin structure of the organism is identified based on the difference between the chromatin structure of the organism and the predetermined factor, correspondence information of the previous generation showing the correspondence between the identified predetermined factor and the chromatin structure is obtained, and the change in the chromatin structure of the target organism is estimated based on the correspondence information of the previous generation, but the invention is not limited to this. When obtaining the above correspondence information, other factors other than the living environment factors, psychological factors, age factors, and sex factors listed as predetermined factors may be included. [Explanation of Symbols]

[0045] 10...Acquisition unit, 20...Storage unit, 30...Calculation unit, 40...Input device, 50...Output device, 100...Biometric information processing device

Claims

1. The differences between the chromatin structure and biological state of the organism at the first time point and the chromatin structure and biological state of the organism at the second time point, which is after the first time point, are determined. Based on the differences in the chromatin structure and biological state of the organism, we identify histone modifications that cause changes in chromatin structure that alter the biological state. Correspondence information is obtained that shows the correspondence between the identified histone modification and the corresponding biological state of the organism. Based on the aforementioned correspondence information, the histone modifications are identified to activate or suppress the expression of a specified biological state in a target organism of the same species as the organism in question. Methods for processing biological information.

2. The organism at the first time point is an individual from an earlier generation than the organism at the second time point. Further determine the difference between the predetermined factor of the living organism at the first time point and the predetermined factor of the living organism at the second time point. Based on the differences in the chromatin structure of the organism and predetermined factors, the predetermined factors that alter the chromatin structure of the organism are identified. We obtain correspondence information from previous generations that shows the correspondence between the identified predetermined factor and the chromatin structure. Based on the correspondence information of the previous generation, the changes in the chromatin structure of the target organism are estimated. The method for processing biological information according to claim 1.

3. The aforementioned organism is the same individual, The aforementioned first point in time is a point in time before a predetermined age, The second time point is a time point later than the predetermined age. The method for processing biological information according to claim 1.

4. A storage unit that stores correspondence information indicating the correspondence between histone modifications in a living organism and the biological state of the living organism corresponding to said histone modifications, When designation information for activating or suppressing the expression of a biological state is input to a target organism of the same species as the aforementioned organism, a calculation unit identifies the histone modification for activating or suppressing the expression of the said biological state based on the corresponding information stored in the memory unit. Equipped with, In the aforementioned correspondence information, the histone modifications that cause changes in chromatin structure that alter the biological state are identified based on the differences between the chromatin structure and biological state at a first time point in the organism and the chromatin structure and biological state at a second time point following the first time point. A biological information processing device.

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