Biological information processing method and biological information processing device

Abstract

In the biological information processing method, the difference between the chromatin structure and the biological state of a living body at a first time point and each of the chromatin structure and the biological state of the living body at a second time point after the first time point is obtained; identifying a histone modification that causes a change in the chromatin structure that changes the state of the organism, on the basis of each difference in the chromatin structure of the organism and the state of the organism; obtaining correspondence information indicating a correspondence between the specified histone modification and the organism state of the organism corresponding to the histone modification; on the basis of the correspondence information, a histone modification for activating or suppressing expression of a target organism of the same type as the organism in the specified organism state is identified.

Description

Technical Field

[0001] The present disclosure relates to a biological information processing method and a biological information processing device. Background Art

[0002] Epigenetics is a mechanism by which changes in gene expression or phenotype are inherited from cells or multicellular organisms to their descendants without changes in DNA sequence. The mechanism of epigenetics is believed to be related to chemical modifications of DNA such as DNA methylation, chemical modifications of histones, and changes in the structure or stability of nucleosomes and chromatin caused by them.

[0003] Patent Document 1 discloses a method of extracting information related to the history of epigenetic modification of an organism, analyzing the extracted information for similarities with other organisms, and predicting and controlling future changes in the state of the organism.

[0004] Prior art literature

[0005] Patent Literature

[0006] Patent document 1: Japanese Patent Application Publication No. 2018-042560. Summary of the invention

[0007] Patent Document 1 does not teach obtaining information on activation and inhibition of biological state expression in a living body by using epigenetic modification.

[0008] The present disclosure has been made in view of the above circumstances, and an object of the present disclosure is to provide a biological information processing method and a biological information processing apparatus capable of obtaining information on activation and inhibition of biological state expression in a living body.

[0009] In the organism information processing method involved in the present disclosure, the differences between the chromatin structure and the organism state of an organism at a first time point and the chromatin structure and the organism state of the organism at a second time point after the first time point are calculated; based on the differences in the chromatin structure and the organism state of the organism, the histone modification that causes the change in the chromatin structure that will change the organism state is determined; corresponding information is calculated, and the corresponding information indicates the correspondence between the determined histone modification and the organism state of the organism corresponding to the histone modification; based on the corresponding information, the histone modification used to activate or inhibit the expression of the specified organism state for a target organism of the same type as the organism is determined.

[0010] The biological information processing device involved in the present disclosure includes: a calculation unit, which calculates the difference between the chromatin structure and the biological state of a biological body at a first time point and the chromatin structure and the biological state of the biological body at a second time point after the first time point, and based on the difference between the chromatin structure and the biological state of the biological body, determines the histone modification that causes the change in the chromatin structure that will change the biological state, and calculates corresponding information, which indicates the correspondence between the determined histone modification and the biological state of the biological body corresponding to the histone modification; and an acquisition unit, which acquires designated information for activating or inhibiting the expression of the biological state of a target biological body of the same type as the biological body, wherein the calculation unit determines the histone modification corresponding to the biological state specified by the designated information based on the corresponding information and the designated information.

[0011] According to the present disclosure, it is possible to obtain information on activation and inhibition of biological state expression in a living body. BRIEF DESCRIPTION OF THE DRAWINGS

[0012] Figure 1 This is a flowchart showing the flow of the biological information processing method according to the present embodiment.

[0013] Figure 2 It is a diagram schematically showing the principle of epigenetics.

[0014] Figure 3 is a diagram showing an example of a neural network.

[0015] Figure 4 This is a functional block diagram showing an example of a biological information processing device according to the present embodiment. DETAILED DESCRIPTION

[0016] Hereinafter, the embodiments of the biological information processing method and the biological information processing device involved in the present disclosure will be described based on the accompanying drawings. In addition, the present invention is not limited to the embodiments. In addition, the constituent elements in the following embodiments include elements that can be easily replaced by those skilled in the art, or substantially the same elements.

[0017] Figure 1 : is a flow chart showing the process of the biological information processing method involved in this embodiment. Figure 1 As shown, the biological information processing method of this embodiment includes a difference detection step (S10), a first histone modification determination step (S20), a corresponding information calculation step (S30), a biological state designation step (S40) and a second histone modification determination step (S50).

[0018] First, the principle of the biological information processing method of this embodiment is described. The biological information processing method of 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 descendants without changes in DNA sequences.

[0019] Figure 2 This diagram schematically shows the principle of epigenetics, showing the chromatin structure in which DNA is wrapped around proteins called histones. Histones are modified by methylation, ubiquitination, phosphorylation, acetylation, etc., which changes the chromatin structure. Due to changes in chromatin structure, the activation and inhibition of gene expression in the state of the organism changes.

[0020] For example, when histones are methylated, the expression of the biological state caused by the gene is suppressed. Histones are formed into a rope (tail shape) of, for example, 20 to 30 amino acids. The amino acids constituting histones become various modification targets. Figure 2 As shown, the histone H3 tail and the histone H4 tail are modified by methylation (Me) and acetylation (Ac), thereby changing the activation and inhibition of the expression of the state of the organism by the gene. Specifically, the amino acids represented by K4, K36, and K79 of the histone H3 tail are methylated, and the transcription of the genetic information from DNA to mRNA is activated. In addition, the amino acids represented by K9 and K27 of the histone H3 tail and the amino acid represented by K20 of the histone H4 tail are methylated, thereby inhibiting transcription.

[0021] Thus, through changes in histone modifications, the expression of the organismal state caused by the gene is activated or inhibited.

[0022] The present inventors have found that changes in chromatin structure may be caused by, for example, predetermined factors. Examples of such predetermined factors include living environment factors based on the latitude, longitude, climate, and other environments in which an organism lives, experience factors based on the experience gained by an organism through life, psychological factors based on the psychological stress, happiness, and other psychological factors of an organism, age factors based on the age of an organism, and gender factors based on the gender of an organism.

[0023] For example, it is known that organisms living in a low-latitude and high-temperature environment for a long time have a high sweating ability. In other words, in this case, it is believed that due to long-term exposure to a high-temperature environment, the chromatin structure of the organism changes, so that the expression of the sweating ability gene is activated.

[0024] In addition, for example, in the case of humans, the brain of a young child is in the middle of growth and cannot form a large-scale and complex brain tissue like the brain of an adult. In the human brain, long-term memories obtained before a predetermined age of about 3 years old after birth are unstable memories made by an immature brain, and therefore disappear with aging. Moreover, old cells are not replaced by new cells, but grow in the form of adding new cells to existing brain cells. This means that the old memory is not cleared due to the generation of nerves, but the memory is reconstructed in the brain due to the addition of new cells, and the old memory cannot be accessed. That is, in the case of humans, it can be considered that since the brain grows after about 3 years after birth, the chromatin structure changes so that the memory of the old cells in the brain cannot be accessed.

[0025] In the above examples, for example, when an organism with low sweating ability lives in a high temperature environment, if the sweating ability can be improved, it can be more adapted to the high temperature environment. In addition, in the human brain, the ability to feel instinctive actions, geomagnetism, etc. may remain in the memory of old cells before reconstruction. If such an ability can be effectively utilized after growth, it may lead to new discoveries, etc. In addition, unlike these examples, in the case of genes that are prone to cancer, diabetes, autoimmune diseases, etc., it is considered useful to estimate the histone modification that inhibits its expression.

[0026] Therefore, in this embodiment, the differences between the chromatin structure and the biological state of the organism at the first time point and the chromatin structure and the biological state of the organism at the second time point after the first time point are calculated, and based on the differences in the chromatin structure and the biological state of the organism, the histone modification that causes the change in the chromatin structure that will change the biological state is determined, and corresponding information is calculated, which indicates the correspondence between the determined histone modification and the biological state of the organism corresponding to the histone modification, and based on the corresponding information, the histone modification used to activate or inhibit the expression of the specified biological state in a target organism of the same type as the organism is estimated.

[0027] First, in the difference detection step S10, each difference between the chromatin structure and the state of the organism at the first time point and the chromatin structure and the state of the organism at the second time point after the first time point is detected. The chromatin structure of the organism can be obtained, for example, by collecting cells of the organism and analyzing the DNA of the collected cells by a known method. The organism information in this embodiment includes information related to the chromatin structure of the organism. In addition, the state of the organism includes the state of the organism that changes according to the change of the chromatin structure, such as the ability of the organism and the onset of the disease. Regarding the state of the organism of the organism, for example, a wearable device that can obtain the state of the organism can also be installed on the organism, and the state of the organism can be obtained from the organism at a specified time. As the state of the organism, for example, walking speed, running speed, muscle mass, heart rate, respiratory rate, blood pressure, body temperature, brain waves, cerebral blood flow, sweating, the presence or absence of cancer cells, etc. can be cited.

[0028] The first time point and the second time point may be any time points. In addition, when the organism is a human being 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 earlier than the predetermined age of approximately 3 years after birth, and the second time point may be a time point later than the predetermined age of approximately 3 years after birth. In this case, changes in the chromatin structure before and after the inability to access the old cell memory in the brain at the predetermined age of approximately 3 years after birth can be appropriately detected. In addition, the organism may also be an animal, plant, or other organism other than a human being.

[0029] The organism for detecting chromatin structural differences can be the same individual as the target organism described below, or it can be an individual of the previous generation of the target organism. In the past, it was believed that the acquired effects brought by the environment would not be inherited to the next generation. For example, smoking changes the structure of lung cells and causes cancer. It is believed that such acquired effects will not be passed on across generations. In other words, epigenetic memory is completely cleared during the division of egg cells. However, in recent years, it has been proven that there is a possibility that acquired effects are actually passed on across generations.

[0030] How to inherit the influence of the day after tomorrow genetically, for example, in people, it is known that H3K27me3 is related to the suppression of gene expression that changes the packaging of DNA in the nucleus, i.e., the chromatin structure. It has been found that even when other epigenetic modifications are eliminated, H3K27me3 modifications are also present in the embryo after fertilization. This means that the trace of the influence brought by the environment of the day after tomorrow is passed on to the offspring by the mother. The inherited epigenetic modification is important for embryonic development. For example, it is known to remove the trigger enzyme that changes the packaging of the DNA of H3K27me3, and the embryo lacking H3K27me3 in the early stage of embryonic development is destroyed before the end of embryonic development. That is, in reproduction, epigenetic information is not only passed down from generation to generation, but also important for the development of the embryo itself.

[0031] It is known that several important developmental genes that are normally turned off during early embryonic development are turned on in embryos without H3K27me3, thereby activating these genes prematurely during egg cell division and disrupting embryonic development. That is, the inherited epigenetic information is required to process and correctly transcribe the embryo's genetic code.

[0032] These indicate that humans inherit mechanisms beyond genes (important genetic regulatory mechanisms that are fine-tuned and may affect the environment and personal lifestyle). In other words, the environmental adaptations acquired by humans during their survival become the basis for inheritance by their offspring through the germ cell series. On the contrary, the collapse of epigenetic mechanisms may cause diseases such as cancer, diabetes, and autoimmune diseases.

[0033] In the first histone modification determination step S20, based on the differences in the chromatin structure and the biological state of the organism detected in the difference detection step S10, a histone modification causing a change in the chromatin structure that will change the biological state is determined.

[0034] In the correspondence information calculation step S30 , correspondence information indicating the correspondence between the identified histone modification and the biological state of the organism corresponding to the histone modification is obtained.

[0035] In addition, for example, when the chromatin structure and biological information of an organism at a first time point and the chromatin structure and biological information of an organism at a second time point are input, the histone modification that causes the change in the chromatin structure that will change the state of the organism can be calculated and output based on the input results, and a neural network that corresponds the output results to the biological information can be generated in advance. Figure 3 is a diagram showing an example of a neural network. Figure 3 The neural network NW shown in the figure outputs third information I3 including the changed state of the organism and fourth information I4 including the histone modification causing the change in the chromatin structure that will change the state of the organism by inputting first information I1 including the chromatin structure and biological information of the organism at the first time point and second information I2 including the chromatin structure and biological information of the organism at the second time point, and corresponds the third information I3 with the fourth information I4. In this case, by inputting the first information I1 and the second information I2 to the neural network NW, corresponding information that corresponds the third information I3 with the fourth information I4 can be obtained, so the difference detection step S10, the first histone modification determination step S20 and the corresponding information calculation step S30 can be quickly performed.

[0036] In the biological state specifying step S40, the biological state to be targeted and information for activating or inhibiting the expression of the biological state are specified for the target biological body. The target biological body is the same as the biological body whose difference is detected in the difference detecting step S10.

[0037] In the second histone modification determination step S50 , based on the correspondence information calculated in the correspondence information calculation step S30 , a histone modification for activating or inhibiting expression of the biological information specified in the biological state specification step S40 with respect to the target organism is determined.

[0038] In addition, when the organism at the first time point is an individual of the previous generation of the organism at the second time point, the difference between the predetermined factor of the organism at the first time point and the predetermined factor of the organism at the second time point can be further obtained independently of the above steps S10 to S50, or in addition to the above steps S10 to S50. In this case, the predetermined factor that changes the chromatin structure of the organism can be determined based on the difference between the chromatin structure of the organism and the predetermined factor, and the corresponding information of the previous generation indicating the correspondence between the determined predetermined factor and the chromatin structure can be obtained. Moreover, for example, the change in the chromatin structure of the target organism can be estimated based on the corresponding information of the previous generation. For example, when the organism of the parent generation gets cancer at the age of 20, there are different parts in the chromatin structure of the organism at the time point of 19 and the time point of 20, and there are also different parts in the predetermined factors such as living environment, habits, psychological factors, etc., the following countermeasures can be taken: in the organism of the child generation, the possibility of getting cancer is reduced by avoiding entering its living environment, habits, and psychological state.

[0039] In addition, for example, when the organism is a human, the first time point and the second time point are the same individual, the first time point is a time point earlier than the predetermined age of about 3 years after birth, and the second time point is a time point later than the predetermined age of about 3 years after birth, through the above steps S10 to S30, it is possible to detect the change in chromatin structure before and after the change in the organism state such as inability to access the old cell memory in the brain at about 3 years after birth, determine the histone modification that causes the change in the chromatin structure, and appropriately obtain the correspondence information between the determined histone modification and the organism state. In this case, in the organism information specifying step S40, for example, when the organism state (ability) such as accessing the old cell memory in the brain is specified, the histone modification corresponding to the specified organism state can be appropriately determined based on the correspondence information. Therefore, by changing the chromatin structure of the target organism based on the determined histone modification, the expression and activation of the organism state such as the target organism accessing the old cell memory in the brain can be performed. Furthermore, although an example in which the predetermined age is approximately 3 years after birth is shown, the present invention is not limited to this, and any age can be set.

[0040] Figure 4 1 is a functional block diagram showing an example of the biological information processing device 100 according to the present embodiment. Figure 4 As shown, the biological information processing apparatus 100 includes a processing device such as a CPU (Central Processing Unit) and a storage device such as a RAM (Random Access Memory) or a ROM (Read Only Memory).

[0041] The biological information processing device 100 includes an acquisition unit 10, a storage unit 20, and a computing unit 30. The biological information processing device 100 may also include 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 receives various operations. The input device 40 is composed of various input devices such as a keyboard, a mouse, a button, a switch, and a touch panel. The input device 40 can input information such as a biological state that becomes a target and information that activates or inhibits the expression of the biological state to the biological information processing device 100. The output device 50 is composed of a display unit and a sound output unit. The output device 50 outputs the processing content in the biological information processing device 100 through text, images, sounds, etc. The acquisition unit 10 acquires various information. The acquisition unit 10 acquires information input by the input device 40, for example. The acquisition unit 10 acquires information received by the communication unit (not shown).

[0042] The storage unit 20 stores various information. The storage unit 20 has, for example, a memory such as a hard disk drive or a solid state drive. In addition, an external storage medium such as a removable disk can be used as the storage unit 20. The storage unit 20 stores various data, applications, and the like such as the neural network and the corresponding information output by the neural network.

[0043] The operation unit 30 performs various operations. The operation unit 30 performs operations corresponding to the second histone modification determination step S50. In addition, by storing the above-mentioned neural network in the storage unit 20, the operation unit 30 can use the neural network to perform the difference detection step S10, the first histone modification determination step S20, and the corresponding information calculation step S30. In addition, the difference detection step S10, the first histone modification determination step S20, and the corresponding information calculation step S30 can be performed by other devices different from the biological information processing device 100. In this case, the corresponding information obtained in advance by other devices can be stored in the storage unit 20.

[0044] As described above, the organism information processing method of the present embodiment obtains each difference between the chromatin structure and the organism state of the organism at a first time point and the chromatin structure and the organism state of the organism at a second time point after the first time point, and based on each difference in the chromatin structure and the organism state of the organism, determines the histone modification that causes the change in the chromatin structure that will change the organism state, obtains corresponding information, and the corresponding information indicates the correspondence between the determined histone modification and the organism state of the organism corresponding to the histone modification, and based on the corresponding information, determines the histone modification used to activate or inhibit the expression of the specified organism state for a target organism of the same type as the organism.

[0045] In addition, the biological information processing device 100 of the present embodiment includes a calculation unit 30 and an acquisition unit 10. The calculation unit 30 calculates the difference between the chromatin structure and the biological state of the organism at a first time point and the chromatin structure and the biological state of the organism at a second time point after the first time point. Based on the difference between the chromatin structure and the biological state of the organism, the histone modification that causes the change in the chromatin structure that will change the biological state is determined, and corresponding information is calculated. The corresponding information indicates the correspondence between the determined histone modification and the biological state of the organism corresponding to the histone modification. The acquisition unit 10 obtains designated information for activating or inhibiting the expression of the biological state of a target organism of the same type as the organism. The calculation unit 30 determines the histone modification corresponding to the biological state specified by the designated information based on the corresponding information and the designated information.

[0046] According to this configuration, the difference 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 after the first time point is obtained, and based on the difference between the chromatin structure and biological state of the organism, the histone modification that causes the change in the chromatin structure that will change the biological state is determined. Therefore, the histone modification can be determined with high accuracy. In addition, based on the corresponding information representing the correspondence between the determined histone modification and the biological state, the histone modification used to activate or inhibit the expression of the biological state of the target organism can be appropriately determined. Thus, the information related to the activation and inhibition of the expression of the biological state in the organism can be appropriately obtained. By changing the chromatin structure of the target organism based on the histone modification estimated in this way, the expression of a predetermined biological state or the inhibition of the expression can be performed on the target organism.

[0047] In the organism information processing method of this embodiment, the organism at the first time point is an individual of the previous generation of the organism at the second time point, and the difference between the predetermined factor of the organism at the first time point and the predetermined factor of the organism at the second time point is further obtained. Based on the difference between the chromatin structure of the organism and the predetermined factor, the predetermined factor that causes the chromatin structure of the organism to change is determined, and the corresponding information of the previous generation indicating the correspondence between the determined predetermined factor and the chromatin structure is obtained. Based on the corresponding information of the previous generation, the change in the chromatin structure of the target organism is estimated. According to this structure, the histone modification caused by the predetermined factor can be determined with high accuracy. In addition, based on the difference obtained in the individual of the previous generation of the target organism, information related to the activation and inhibition of the expression of the organism state of the individual of the next generation can be appropriately obtained. In addition, by understanding the changes in histone modifications caused by the changes in the chromatin structure of the parent generation before the birth of the child, countermeasures such as artificial histone modification can be carried out at a specific period in the child generation. In addition, for example, when the parent generation of organisms has different parts in the chromatin structure at the first time point and the second time point, and also has different parts in the predetermined factor, the following countermeasures can be taken: in the offspring generation of organisms, by living in a way that avoids the predetermined factor, the expression of specific organism information can be activated or inhibited.

[0048] In the biological information processing method of this embodiment, the biological subject is the same individual, the first time point is a time point before a predetermined age, and the second time point is a time point after the predetermined age. According to this configuration, by making the difference of histone modification of the chromatin structure of the same individual that changes before and after the predetermined age correspond and obtaining correlation, the histone modification used to activate the expression of the biological state obtained before the predetermined age can be appropriately obtained.

[0049] The technical scope of the present disclosure is not limited to the above-mentioned embodiments, and can be appropriately changed within the scope of the main purpose of the present disclosure. For example, in the above-mentioned embodiments, the following situation is used as an example for explanation: the difference between the predetermined factor of the organism at the first time point and the predetermined factor at the second time point after the first time point is further obtained, and based on the difference between the chromatin structure of the organism and the predetermined factor, the predetermined factor that causes the chromatin structure of the organism to change is determined, and the corresponding information of the previous generation indicating the correspondence between the determined predetermined factor and the chromatin structure is obtained, and the change in the chromatin structure of the target organism is estimated based on the corresponding information of the previous generation, but it is not limited to this. In the case of obtaining corresponding information, other factors different from the living environment factors, psychological factors, age factors and gender factors as predetermined factors may be included.

[0050] Industrial Applicability

[0051] The biological information processing method and the biological information processing apparatus according to the present disclosure can be used in a processing apparatus such as a computer, for example.

[0052] Explanation of symbols

[0053] 10: acquisition unit; 20: storage unit; 30: calculation unit; 40: input device; 50: output device; 100: biological information processing device.

Claims

1. A biological information processing method, wherein: Determining the difference between the chromatin structure and the biological state of the organism at a first time point and the chromatin structure and the biological state of the organism at a second time point after the first time point; Based on the differences in the chromatin structure of the organism and each of the states of the organism, determining histone modifications that cause changes in the chromatin structure that will alter the state of the organism; obtaining correspondence information indicating correspondence between the determined histone modification and an organism state of the organism corresponding to the histone modification; Based on the correspondence information, the histone modification for activating or inhibiting expression of the designated organism state in a target organism of the same species as the organism is determined.

2. The biological information processing method according to claim 1, wherein: The organism at the first time point is an individual of the previous generation of the organism at the second time point, further determining the difference between the predetermined factor of the organism at the first time point and the predetermined factor of the organism at the second time point, determining the predetermined factor that changes the chromatin structure of the organism based on the difference between the chromatin structure of the organism and the predetermined factor, obtaining the previous generation correspondence information indicating the correspondence between the determined predetermined factor and the chromatin structure, Based on the corresponding information of the previous generation, changes in the chromatin structure of the target organism are estimated.

3. The biological information processing method according to claim 1, wherein: The organisms are the same individual, The first time point is a time point before a predetermined age, The second time point is a time point after the predetermined age.

4. A biological information processing device, comprising: a calculation unit that obtains each difference between the chromatin structure and the biological state of the organism at a first time point and the chromatin structure and the biological state of the organism at a second time point after the first time point, determines the histone modification that causes the change in the chromatin structure that will change the biological state based on each difference in the chromatin structure and the biological state of the organism, and obtains corresponding information that indicates the correspondence between the determined histone modification and the biological state of the organism corresponding to the histone modification; as well as an acquisition unit, which acquires designated information for activating or inhibiting expression of an organism state for a target organism of the same species as the organism, The calculation unit specifies the histone modification corresponding to the biological state specified by the specifying information based on the correspondence information and the specifying information.

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