JP2005222501A - Simulation system, display system, database and program regarding network in living body - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide technology regarding a simulation system which grasps change of a network in the living body with high accuracy. <P>SOLUTION: The simulation system of the network in the living body is provided with a network information acquisition part 123 which acquires a network model in the living body having a plurality of pieces of element data including names of elements in the living body and element states expressing chemical states or physical states in the elements in the living body, an element state update part 18 which adds or updates one or more pieces of element data according to a user's request, a network update part 19 which sequentially updates the element data included in the network in the living body in consideration of update of the element states by the element state update part 18 and reconstructs element relation in the network in the living body, and an output part 17 which presents information regarding the reconstructed network model in the living body to a user. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

  The present invention relates to a simulation system, a display system, a database, and a program related to an in vivo network.

  An in vivo network is a gene regulatory network that describes the relationship in which a gene controls another gene, a protein interaction network that describes a relationship in which two proteins interact, and that a compound becomes another compound by an enzyme It is a generic name for the network representation of element states and element relationships of in vivo elements such as metabolic pathways describing reactions.

  In recent years, research on in-vivo networks has been actively conducted, and some of the results have been made public via the Internet. Since the number of genes, proteins, and compounds in vivo is enormous, there is a need for a system that enables researchers to search and partially display relationships of interest from in vivo networks.

  An example of a conventional in-vivo network simulation system is as follows.

  For example, as a conventional in vivo network simulation system, element information and relation information of genes and proteins accumulated in a database are used to reconfigure a network with elements as nodes and relationships as arcs, and display a network diagram on the display There is a system to do. In this system, network editing can be performed when a user inputs an editing command from an input device. In addition, the user can select relationship information stored in the database and selectively display only a specific relationship, and can specify a start point element and an end point element to reconfigure the network (for example, Patent Documents) 1).

In addition, as a conventional in vivo network simulation system, there is also a system that displays an in vivo network by assigning element figures to the types and states of in vivo elements, and interactions between in vivo elements (for example, Patent Documents). 2).
JP 2002-91991 A JP 2003-109019 A

  Since in vivo networks are complex, it is important for users who are studying in vivo networks to know the effects of changes in the state of in vivo elements. For example, the following cases can be considered. Phosphorylated protein A and phosphorylated protein B bind to form a protein complex AB. The complex is attached to the chromosome and gene C is expressed. Protein D is further expressed from the expressed gene C.

  In such a case, the in vivo network such as a gene or protein is in a state where a relationship between the elements is established and the state of another in vivo element changes when the condition is satisfied. Is formed.

  In an in vivo network, generally, one in vivo element can have a plurality of element states. For example, even in the same in vivo element, there can be a phosphorylated state, a non-phosphorylated state, an ionized state, a non-ionized state, and the like. Alternatively, a plurality of states may have a complex influence, such as being in a phosphorylated state when present in the cell membrane, but not elsewhere.

  Therefore, it is very important for the user to establish the element relation and grasp the influence range by the change of the element state of the in-vivo element.

  The conventional in vivo network simulation system has room for improvement in that it is difficult to grasp the range of influence due to a change in the state of one or more in vivo elements such as genes and proteins. This is because the in-vivo network is not searched in consideration of the establishment of the element relation due to the change in the element state between the in-vivo elements.

  The conventional in-vivo network simulation system described in Patent Document 1 and Patent Document 2 only displays data stored in a network format as it is, and element relationships between in-vivo elements due to changes in element states of in-vivo elements. Whether or not is satisfied is hardly considered. Therefore, there is room for improvement in that it is difficult to grasp the range of influence due to the state change of the in-vivo element.

  For example, when the above example is displayed in a conventional system, only the in vivo network in which protein A, protein B, protein complex AB, gene C, and protein D are nodes and these relationships are connected by an arc is displayed. .

  On the other hand, in an actual living body, when protein A is only in a phosphorylated state or protein B is only in a phosphorylated state, the in vivo network may not be formed. For example, when protein A is in a phosphorylated state and protein B is in a phosphorylated state, it is assumed that an elemental relationship between in vivo elements is first established and an in vivo network is formed.

  Therefore, in the in-vivo network simulation system described in Patent Document 1, what element relationship between which in-vivo elements is established and which in-vivo elements are in what state by changes in element states of in-vivo elements It is difficult to grasp the chained influence range, such as whether to change, in a form that accurately reflects the actual phenomenon in the living body.

  In addition, in the conventional in vivo network simulation system described in Patent Document 2, element graphics are assigned and displayed to element relations and element states between in vivo elements, but the conditions for establishing the element relations are not considered. . For this reason, it is possible to grasp what element state the in-vivo element has, but it is difficult to grasp to what extent the element state affects and in what order.

  That is, in the in-vivo network simulation system described in Patent Literature 2, only in-vivo elements are assigned to nodes, element relations are arcs, and graphics indicating element states are only assigned to arc heads. Therefore, since the condition for establishing the element relationship is not taken into consideration, the element state between the two in vivo elements can be grasped, but it is difficult to grasp the change in the element state between many in vivo elements.

  The present invention has been made in view of the above circumstances, and an object thereof is to provide a technique related to a simulation system capable of accurately grasping a change in an in vivo network.

  According to the present invention, a plurality of in-vivo elements are included, and the in-vivo elements are represented by an element relationship represented by a state change between in-vivo elements, a cause element before the state change, and a result element after the state change. A simulation system that analyzes an in vivo network model that describes the relationship between the in vivo elements and analyzes how the element relation between in vivo elements changes when the state of any in vivo element changes. An in-vivo network model having a plurality of element data including in-vivo elements and element states of the in-vivo elements, and acquiring the in-vivo network model, and adding or updating the element data according to a user request, In consideration of the update of the element data, a simulation system including a search unit for reconstructing the in-vivo network is provided.

  According to the present invention, since it is a configuration for grasping how the element relation between the in vivo elements changes due to the change in the element state of the in vivo element, one or more added or updated according to the user's request The change in the in-vivo network starting from the element data can be grasped in a chain manner, and the change in the in-vivo network can be grasped with high accuracy.

  As mentioned above, although the structure of this invention was demonstrated, what combined these structures arbitrarily is effective as an aspect of this invention. Moreover, what converted the expression of this invention into the other category is also effective as an aspect of this invention.

  It should be noted that any combination of the above-described constituent elements and a conversion of the expression of the present invention between a method, an apparatus, a system, a recording medium, a computer program, etc. are also effective as an aspect of the present invention.

  ADVANTAGE OF THE INVENTION According to this invention, the technique regarding the simulation system which can grasp | ascertain the change of a biological network accurately can be provided.

  The simulation system of the present embodiment includes a plurality of in-vivo elements, and this in-vivo is represented by an element relationship represented by a state change between in-vivo elements, a cause element before the state change, and a result element after the state change. A simulation system that analyzes in vivo network models that describe the relationship between elements and analyzes how the element relationship between in vivo elements changes when the state of any in vivo element changes. A network information acquisition unit for acquiring the in-vivo network model having a plurality of element data including a name of an in-vivo element and an element state representing a chemical state or a physical state of the in-vivo element, and a user request Depending on the element state update unit that adds or updates one or more of this element data and the element state update by this element state update unit. A network update unit that sequentially updates element data included in the in-vivo network, reconstructs element relationships in the in-vivo network, and an output unit that presents information regarding the reconstructed in-vivo network model to the user. The simulation system provided may be sufficient.

  Even with such a configuration, it is a configuration for grasping how the element relation between the in vivo elements changes due to the change in the element state of the in vivo element. The change in the in-vivo network starting from the above element data is grasped in a chain manner, and the change in the in-vivo network can be grasped with high accuracy.

  In the simulation system of the present embodiment, the network update unit generates a new element relationship using the added or updated element data as a cause element, and transmits element data corresponding to a result element of the element relationship to the element data. You may comprise so that operation added to the in-vivo network may be performed sequentially.

  With this configuration, in order to sequentially update the element data contained in the in vivo network in the downstream direction in consideration of the conditions for establishing the element relation between the in vivo elements, the state change of in vivo elements such as genes and proteins The contents and range of the effect on the in-vivo network in the downstream direction can be presented by simulation.

  Further, the simulation system of the present embodiment includes an element table for storing element data, a satisfaction condition specified by element data of one or more cause elements, and element data of a result element generated when this satisfaction condition is satisfied And the network updating unit extracts the element data of the causal element constituting the establishment condition from the in-vivo network model with reference to the element relation table. The element data of the result element corresponding to the extracted element data of the cause element may be generated, and the operation of adding the generated element data to the in-vivo network may be sequentially executed.

  With such a configuration, it is possible to perform the update in the downstream direction sequentially, so the contents and range of the effects on the in vivo network in the downstream direction due to changes in the state of in vivo elements such as genes and proteins are simulated. Can be presented.

  Alternatively, in the simulation system of the present embodiment, the network update unit generates a new element relationship using the added or updated element data as a result element, and element data corresponding to a cause element of the element relationship May be configured to sequentially execute the operation of adding the above to the in-vivo network.

  With this configuration, in order to sequentially update the element data contained in the in vivo network in the upstream direction in consideration of the conditions for establishing the element relationship between the in vivo elements, the state change of in vivo elements such as genes and proteins The contents and range of the effect on the in vivo network in the upstream direction can be presented by simulation.

  In addition, the simulation system of the present embodiment includes an element table that stores element data, a formation result specified by element data of one or more result elements, and element data of a cause element that causes the formation result to be generated. And the network update unit extracts the element data of the result elements constituting the establishment result from the in-vivo network model with reference to the element relation table. The element data of the cause element corresponding to the element data of the extracted result element may be generated, and the operation of adding the generated element data to the in-vivo network may be sequentially executed.

  With this configuration, it is possible to sequentially perform the above-mentioned update in the upstream direction, so the contents and range of the effects on the in-vivo network in the upstream direction due to changes in the state of in vivo elements such as genes and proteins are simulated. Can be presented.

  In the simulation system according to the present embodiment, the element state update unit adds or updates two or more pieces of the element data according to the user's request, and the network update unit includes the element state. The element data included in the in-vivo network is sequentially updated in consideration of the update of the element state by the updating unit, and the element relation connecting the two or more element data in the in-vivo network is reconstructed. It may be configured.

  With this configuration, it is possible to reconstruct an element relationship that connects two or more element data included in the in-vivo network in consideration of a condition for establishing an element relationship between in-vivo elements. Pathways that connect in vivo elements such as genes and proteins inside can be presented by simulation.

  The simulation system according to the present embodiment may further include an element data storage unit that sequentially stores addition or update of the element data as a change process of the in-vivo element.

  With such a configuration, the change process of the in vivo element can be acquired later and presented to the user, so the contents of the influence on the in vivo network due to the state change of the in vivo element such as a gene or protein The range can be presented to the user at a suitable time by simulation.

  The simulation system according to the present embodiment may further include an established element relation storage unit that sequentially stores element relation records in which the establishment condition or the establishment result is established in the element relation table as an element relation establishment process.

  With such a configuration, since the formation process of the element relations can be acquired later and presented to the user, the contents of the influence on the in vivo network due to the state change of the in vivo elements such as genes and proteins and its contents The range can be presented to the user at an appropriate time by simulation.

  The simulation system of the present embodiment further includes an unestablished element relation storage unit that stores an unestablished element relation record in which only a part of the established condition or the establishment result is established in the element relation table as an unestablished element relation. You may prepare.

  With such a configuration, since it is possible to acquire the unestablished element relationship later and present it to the user, the element state of any in vivo element relative to the element state of the in vivo element input by the user If it is added, it can be shown to the user at an appropriate time whether the range of influence on the in-vivo network will be further expanded.

  The simulation system of the present embodiment may be configured to allow one or more different element data having only one of the names or element states of the in-vivo element to be the same as the element data. .

  With this configuration, it is possible to handle an in-vivo network in which the same in-vivo element can have a plurality of element states. It is possible to grasp a chained influence range such as which element relation is established and which in vivo element causes what kind of state change in a form that accurately reflects an actual phenomenon in the living body.

  In the simulation system of this embodiment, the in vivo element includes one or more in vivo elements selected from the group consisting of genes, DNA, RNA, proteins, low molecular compounds, ions, and complexes thereof. The above element states are phosphorylation, ionization, GTP binding, GDP binding, dephosphorylation, activation, inactivation, expression activation, expression suppression, binding, degradation, transcription, translation, intracellular station It may include one or more element states selected from the group consisting of presence, in-vivo tissue name, environmental condition, and composite conditions thereof.

  With such a configuration, various types of in-vivo elements or element states can be handled. Therefore, what element relationships between which in-vivo elements are established by changing the element states of in-vivo elements, and which It is possible to grasp the chained influence range such as what kind of state change occurs in the living body element in a form that accurately reflects the actual phenomenon in the living body.

  Further, in the simulation system of the present embodiment, the output unit acquires a change process of the element data stored in the element data storage unit, and stores the above-described element data stored in the established element relationship storage unit. The establishment process of the element relationship may be acquired, and a simulation result representing the effect of the one or more element data added or updated according to the user's request may be generated and presented to the user. .

  With such a configuration, the change process of the element data and the establishment process of the element relation can be collectively presented to the user, so that the simulation result can be presented to the user in an easily understandable form.

  Further, in the simulation system of the present embodiment, the output unit obtains an unestablished relationship of the element relationship stored in the unestablished element relationship storage unit, and adds or adds to the user request. You may comprise so that the simulation result showing the range which may be influenced by the updated one or more said element data is further produced, and it shows to said user.

  With such a configuration, the above-described incomplete element relationship can be acquired and presented to the user, so what kind of in vivo element state is added to the in vivo element state input by the user Then, it can be shown to the user in an easy-to-understand manner whether the range of influence on the in-vivo network is further expanded.

  Further, in the above simulation system, the output unit is configured to generate the simulation result as an animation in a display order associated with an order of establishment of the element relations and present the result to the user. May be.

  With such a configuration, an animation reflecting the order in which the above element relations are established can be presented to the user, so that the simulation result can be presented to the user in a more easily understandable form.

  The simulation system of the present embodiment further includes an experiment result correspondence storage unit that stores experimental data including element data, experiment conditions, and experiment results associated with each other. In response to the request, a combination of one or more experimental conditions and experimental results is acquired, element data associated with the combination is acquired from the experimental result correspondence storage unit, and element data of the in vivo network is added or You may comprise so that it may update.

  With such a configuration, element data corresponding to a combination of experimental conditions and experimental results can be acquired, and element data of the in-vivo network can be added or updated, so that it corresponds to a combination of experimental conditions and experimental results. The contents and range of the influence on the in-vivo network due to the state change of the in-vivo element can be presented by simulation.

  In addition, the display system of the present embodiment includes a plurality of in-vivo elements, and this is represented by an element relationship represented by a state change between in-vivo elements, a cause element before the state change, and a result element after the state change. A display system for displaying an in-vivo network model describing a relationship between in-vivo elements, including a name of the in-vivo element and an element state representing a chemical state or a physical state of the in-vivo element It may be a display system including an output unit that displays a cause element and a result element composed of element data and an establishment condition composed of one or a plurality of element data for establishing this element relation in association with each other. .

  With such a configuration, the element data constituting the in-vivo network model and the conditions for establishing the element relation can be collectively presented to the user, so that the chain of element data in the in-vivo network model can be easily understood. The in-vivo network model can be presented to the user.

  In addition, the database of the present embodiment includes a plurality of in-vivo elements, and this generation is based on an element relationship represented by a state change between in-vivo elements, a cause element before the state change, and a result element after the state change. A database that accumulates in-vivo network models describing relationships between in-vivo elements, an element table that stores element data, a fulfillment condition specified by element data of one or more causal elements, and the fulfillment condition The database may include an element relation table including element data of result elements that are sometimes generated.

  By using a database having such a configuration, it is possible to accurately perform the simulation of the in-vivo network in consideration of the conditions for establishing the element relationships of the in-vivo elements.

  The program of this embodiment includes a plurality of in-vivo elements in a computer, and an element relationship represented by a state change between in-vivo elements, a cause element before the state change, and a result element after the state change. Analyzes how the relationship between in vivo elements changes when the state of any in vivo element changes, using the in vivo network model describing the relationship between the in vivo elements as described above The in-vivo network model having a plurality of element data including a name of an in-vivo element and an element state representing a chemical state or a physical state of the in-vivo element Network information acquisition means for acquiring the element state update means for adding or updating one or more of the element data in response to a user request, and the element state update Updating the element data included in the in-vivo network in consideration of the update of the element state by the unit, and re-establishing the element relationship in the in-vivo network, and the re-established in-vivo network model It is good also as a program which functions as an output means which presents the information regarding to said user.

  With such a configuration, the computer can grasp how the element relation between the in vivo elements changes due to the change in the element state of the in vivo element, and is added or updated according to the user's request. In addition, the change in the in-vivo network starting with one or more element data can be grasped in a chained manner, and the change in the in-vivo network can be grasped with high accuracy.

  In the present specification, the element relationship means a relationship represented by a state change between in-vivo elements, a cause element before the state change, and a result element after the state change. The in-vivo network includes a plurality of in-vivo elements, and the in-vivo network has an element relationship represented by a state change between in-vivo elements, a cause element before the state change, and a result element after the state change. Assume that the relationship between elements is described. Furthermore, the in-vivo network simulation system is a system that analyzes in-vivo networks and analyzes how the element relationship between in-vivo elements changes when the state of any in-vivo element changes. It shall be.

  Here, in the present specification, the establishment condition of the element relationship is also simply referred to as the establishment condition. The condition for establishing the element relationship is a combination of element data including one or a plurality of in-vivo elements and an element state to be satisfied in order to establish the element relationship. In the present specification, an in-vivo element may be simply referred to as an element. Furthermore, in this specification, element data is a concept including an in-vivo element and an element state of the in-vivo element. Further, the element data may further include other data. For example, data regarding the number of chains may be included. Alternatively, related journal information may be included.

  In the present specification, the in vivo element means any molecule existing in the living body such as a gene, DNA, RNA, protein, low molecular compound, ion, and a complex thereof. Many in vivo elements are composed of natural polymers, but are not limited to proteins, lipids, carbohydrates, and natural polymers, and may be low molecular weight, inorganic, or metal ions. It may be.

  In the present specification, the element state means phosphorylation, ionization, GTP binding, GDP binding, dephosphorylation, activation, inactivation, expression activation, expression suppression, binding, degradation, transcription, It means a physical state or a chemical state that can be taken by in vivo elements such as translation, subcellular localization, in vivo tissue name, environmental conditions, and combined conditions thereof.

  Further, in the present specification, the causal element means one or a plurality of element data constituting a condition for establishing a certain element relationship. That is, the cause element is a set of element data before the state change.

  Further, in this specification, a result element means one or a plurality of element data that constitutes a result of establishment of a certain element relationship. That is, the result element is a set of element data after the state change.

  In the case of performing the simulation to the downstream side, it is assumed that the element relation is established when the element relation satisfies the establishment condition. A combination of element data including one or a plurality of in-vivo elements and element states obtained as a result of the establishment is called an establishment result. At this time, the condition for establishing the element relationship includes one or more cause elements. In addition, the establishment result of the element relation includes one or a plurality of result elements.

  Or, as will be described later, in the case of performing a simulation to the upstream side, when this element relation satisfies the establishment result, it is said that the element relation is established. Unlike the simulation to the downstream side, a combination of element data including one or a plurality of in-vivo elements and element states that can change to the establishment result via the established element relation is called an establishment condition. . Also at this time, the formation condition of the element relationship includes one or a plurality of causal elements. In addition, the establishment result of the element relation includes one or a plurality of result elements.

  The chain is a connection between the establishment of a certain element relationship and a change in the element state of the in vivo element. The number of chains is the number of chains.

  In this specification, the database is also simply referred to as DB.

  Hereinafter, embodiments of the present invention will be described with reference to the drawings. In all the drawings, the same reference numerals are given to the same components, and the description will be omitted as appropriate.

<First Embodiment>
FIG. 1 is a block diagram showing a configuration of an in-vivo network simulation system in the present embodiment.

  The in vivo network simulation system 10 stores an element relation table that constitutes an in vivo network model including a plurality of in vivo elements based on element data including in vivo elements and element states input by a user. A simulation is performed by referring to the database 23 and searching for a chain in consideration of the condition for establishing the element relationship.

  When searching this chain, the process of establishing the established element relation and the process of changing the element state to be added or updated are sequentially held as the search process. By reconfiguring the network and presenting it to the user based on this search process, it is possible to grasp the chain change of the in-vivo network caused by the change of the element state. Further, based on the search process, it is possible to present to the user what kind of in vivo element state is added to further expand the range of influence on the in vivo network.

  Specifically, the in-vivo network simulation system 10 acquires an in-vivo network model having a plurality of element data including a name of an in-vivo element and an element state representing a chemical state or a physical state of the in-vivo element. Network information acquisition unit 123, input unit 11 that receives input from the user, element state update unit 18 that adds or updates one or more element data in response to a user request, and element state update by the element state update unit In consideration of updating, the element data included in the in-vivo network is sequentially updated, the network update unit 19 for reconstructing the element relation in the in-vivo network, and the element relation table including the information on the in-vivo elements and the element relations In-vivo network model DB 23 and element states in searching for linkages in the in-vivo network The element state storage unit 21 that holds the change process, the formation element relationship storage unit 22 that holds the formation process of the element relation in the search of the chain in the in vivo network, and the result of the change process of the element state and the formation process of the element relation The display processing unit 13 for reconfiguring the network and the display device 14 for displaying the network and the like to the user.

  In addition, a network information storage unit 27 that stores information on the in-vivo network that the network information acquisition unit 123 has acquired in advance from the in-vivo network model DB 23 may be provided. At this time, instead of accessing the in-vivo network model DB 23, the network acquisition unit 123 may access the network information storage unit 27 and acquire the in-vivo network model.

  In the present embodiment, a description will be given centering on a form in which the in-vivo network model 23 is accessed via the network acquisition unit 123, but the present invention is not particularly limited to such a form. That is, the data acquired from the network information storage unit 27 via the network acquisition unit 123 is preferably used in any functional block referred to in the present embodiment, instead of the data acquired from the in-vivo network model 23. it can.

  In the present invention, also in other embodiments, as in the present embodiment, the network information acquisition unit includes a network information storage unit that stores in-vivo network information acquired from the in-vivo network model DB in advance. It may be provided. Similarly in other embodiments, the network acquisition unit may access the network information storage unit and acquire the in-vivo network model instead of accessing the in-vivo network model DB.

  The network information acquisition unit 123, the element state update unit 18, and the network update unit 19 constitute a search unit 12 that searches for a chain in the in-vivo network.

  In addition, the display processing unit 13 and the display device 14 constitute an output unit 17 that outputs information on the reconstructed in-vivo network model to the user. Here, the output device included in the output unit 17 is not limited to the display device 14. For example, instead of a display device using a cathode ray tube display, a liquid crystal display, a plasma display panel, etc., various printers such as inkjet printers and laser printers may be used, or websites on various networks such as the Internet, WAN, and LAN. An output device such as a modem or a router may be used to display the result.

  Each component of the in-vivo network simulation system 10 is a component that is specifically realized by cooperation of software and hardware configured to operate on a computer under program control.

  Here, the in-vivo network model DB 23 accumulates information on in-vivo elements such as in-vivo element names and information on element relationships such as establishment conditions and result elements. The in-vivo network model DB 23 may be stored in a recording medium such as a CPU cache, memory, or HD built in the system of the present embodiment, but is not limited to the built-in, and is not limited to FD, CD, It may be stored in a recording medium such as MD, MO, or DVD, or may be stored in a server connected to the Internet.

  The method for constructing the in vivo network model DB 23 is not particularly limited, and various molecular biology-related databases provided by, for example, the Human Genome Center of the University of Tokyo Medical Science Institute can be used. Biological researchers may create their own data by referring to such information and papers.

  In addition, the element state storage unit 21 displays the change process of the element state that is changed by the establishment of the element relation when the search unit 12 including the element state update unit 18 and the network update unit 19 searches for a chain in the in vivo network. Hold.

  The established element relation storage unit 22 is a process of establishing an element relation established by a change in the element state when the search unit 12 including the element state update unit 18 and the network update unit 19 searches for a chain in the in vivo network. Hold.

  Both the element state storage unit 21 and the established element relationship storage unit 22 may be CPU caches, memories, HDs, or other recording media built into the system of the present embodiment, but are not limited to being built in. , FD, CD, MD, MO, DVD and the like, or a folder in a server connected to the Internet.

  Next, an outline of the operation of these components will be described.

  The input unit 11 receives the element data from the user, and passes the element data to the search unit 12 including the network information acquisition unit 123, the element state update unit 18, and the network update unit 19 (11012).

  The search unit 12 receives element data from the input unit 11 (11012), refers to the in-vivo network model DB 23 by the network information acquisition unit 123 (23012), and searches for a chain in consideration of the establishment condition. The chain search is performed as follows. With reference to the in-vivo network model DB 23, the element state update unit 18 and the network update unit 19 verify whether the element relationship is established. If it is established, the element relation is further verified based on the result element, and the search is sequentially performed until no element relation is established. The search unit 12 holds the establishment process of the element relationship in the established element relation storage unit 22 by the element state update unit 18 (12022), and holds the change process of the element state in the element state storage unit 21 by the network update unit (12021). ). When the search is completed, the display processing unit 13 is notified (12013).

  The output unit 17 reconfigures the network from the search result obtained by the search unit 12 and outputs the result to the user. The result is output as follows. The display processing unit 13 refers to the established element relation storage unit 22 and the element state storage unit 21 (22013, 21013), creates information such as nodes and arc positions for reconfiguring and displaying the network, It is passed to the display device 14 (13014).

  The display device 14 receives the information passed by the display processing unit 13 (13014) and presents it to the user.

  The in-vivo network simulation system 10 operates as follows. First, the input unit 11 receives an element and an element state from the user and passes them to the search unit 12. Next, the search unit 12 refers to the in-vivo network model DB 23 by the network information acquisition unit 123, and searches for a chain while considering the establishment condition. The search process is held in the element state storage unit 21 and the established element relationship storage unit 22 by the element state update unit 18 and the network update unit 19. The search unit 12 notifies the display processing unit 13 that is a component of the output unit 17 that the search has been completed. Next, the display processing unit 13 creates information for displaying the network based on the information in the element state storage unit 21 and the established element relationship storage unit 22 and passes the information to the display device 14. Is displayed.

  Next, the overall operation of the present embodiment will be described in more detail with reference to FIG.

  First, the input unit 11 receives designation of element data including a set of one or more in-vivo elements and element states from the user. If the maximum number of chains is specified, it is received. The received information is passed to the search unit 12 (11012).

  Specify one or more element data that the user is interested in. In addition, it is possible to designate all element states in a specific in vivo element or all in vivo elements in a specific element state. The maximum number of chains specifies the number of chains to be searched.

  FIG. 5 is a diagram illustrating an example of a screen for obtaining information specified by the input unit 11 in the present embodiment. The input unit 11 receives a user designation through such a graphical user interface, for example. This graphical user interface includes a designated portion of element data and a designated portion of the maximum chain number. In the element data designation part, an element and an element state can be added by pressing an add button, and a plurality of element data can be designated. Furthermore, when specifying all elements and element states, “*” is specified.

  This designation method is an example, and the in vivo network model DB 23 may be referred to in advance, and elements and element states may be selected from a list. On the other hand, the designation part of the maximum number of chains specifies whether or not to designate the maximum number of chains, and the number of chains in the case of designation. This designation method is an example, and the maximum number of chains may be set in advance, or the maximum number of chains may not be designated. In the example of FIG. 5, the input unit 11 includes three elements “A”, an element state “phosphorylation”, an element “B”, an element state “phosphorylation”, an element “I”, and an element state “ionization”. The internal element, element state, and maximum chain number “5” are received. The received element data and the maximum number of chains are passed to the search unit 12.

  Returning to FIG. 1, the search unit 12 receives element data from the input unit 11. If the maximum number of chains is specified, it is received (11012). Next, the network information acquisition unit 123 refers to the in-vivo network model DB 23 (23012), and searches for a chain in consideration of the conditions for establishing the element relationship. Further, the search unit 12 holds this search process in the element state storage unit 21 and the established element relationship storage unit 22 by the element state update unit 18 and the network update unit 19 (12021, 12022). When the chain search is completed, the display processing unit 13 that is a component of the output unit 17 is notified that the search is completed (12013).

  The in-vivo network model DB 23 has an element table and an element relation table for storing information on in-vivo elements and element relationships in the in-vivo network. The element table shows information on in-vivo elements in the in-vivo network, and has element names and types for identifying each in-vivo element.

  The information for identifying the in-vivo element may be an ID indicating the element instead of the element name. In addition, an element name alias or function classification may be included. The element relationship table shows the relationship between two in-vivo elements, and has a relation name for identifying each element relation, a connection-source in-vivo element name, a connection in-vivo element name, an establishment condition, and a result element. The information for identifying the element relationship may be an ID indicating the element relationship instead of the relationship name. In addition to this, classification of element relations and the like may be included.

  FIG. 2 is a diagram illustrating an example of an in-vivo network model database. This in vivo network model DB includes an element table and an element relation table. The element table stores element names and types. For example, the first record represents an in vivo element whose element name is “A” and whose type is “protein”. In the element relation table, the relation name, the connection source element name, the connection destination element name, the establishment condition, and the element state at the time of establishment (combining with the connection destination element name constitute the result element) are accumulated. For example, the first record is an element relationship in which the relationship name is “Arc 1”, the connection source element name is “A”, and the connection destination element name is “AB”. If there is a causal element that the element “A” is in the element state “phosphorylated” and a causal element that the element “B” is in the element state “phosphorylated” from the satisfaction condition, this element relation Indicates that a result element is obtained in which the element state “AB” becomes the element state “combined”.

  Here, the establishment condition specifies element data including a combination of a plurality of in-vivo elements and element states by a logical operator. The establishment condition includes element data related to the connection source element. For example, the condition for establishing the relation name “arc 1” in the figure is that the element state “phosphorylation” relating to the connection source element “A” is the condition, and the element state “phosphorylation” relating to “B” that is not the connection source element The logical product is specified. In this way, element state changes of a plurality of in vivo elements can be set as conditions. Further, there may be an elemental relationship whose establishment condition is unknown, such as an arc 10 in the figure.

  The element state when the result element is established designates the element state of the connection destination element when the element relation is established. Like the arc 10 in the figure, there may be an element relationship in which the element state when the result element is established is unknown.

  The element state storage unit 21 holds the process of changing the element state caused by the sequentially established element relationship when the search unit 12 searches the chain. The information to be held includes element data such as in-vivo elements and element states, the number of chains in which the element state has changed, and the search status of the element state.

  FIG. 4 is a diagram illustrating an example of the element state storage unit and the established element relationship storage unit in the present embodiment. An example of the element state storage unit 21 is shown in FIG. It has an element status table, and holds the element name, element status, the number of chains in which the element status has changed, and the search status (a field for recording whether or not it has been read). The search status is progress information indicating whether the search unit 12 has searched for a chain based on the element state of the record. For example, the first record indicates that an in-vivo element having an element state “A” and an element state “phosphorylated” has undergone a state change when the number of chains is “0”, and has already searched for a chain based on the element state. ing.

  The established element relationship storage unit 22 holds the establishment process of the element relationships that are sequentially established by the chain search in the search unit 12. The information to be held includes the relation name, the establishment condition, the result element that changes state when established, the establishment state of the element relation, and the chain number at the time of establishment.

  An example of the establishment element relationship storage unit 22 is shown in FIG. Has an established element relation table, relation name, establishment condition, element name that changes state when established, element state when established (result element is combined with element name when established), established state of element relation, established Holds the chain number. The establishment condition column is rewritten when there is a change in the element state in the chain search by the search unit 12. When there is a change in the element state, the corresponding part is replaced with “True”. The element name that changes state when established is the connection destination element of the element relationship in the in vivo network model DB 23.

  For example, the first record is the relation name “arc 1”, and referring to the establishment condition, all element states corresponding to arc 1 have already changed, arc 1 has been established, and the number of established chains is “1”. ". This method is an example, and an attribute for holding the changed element state may be prepared separately.

  Next, the operation of the search unit 12 will be described in detail with reference to the block diagram of FIG. 19 and the flowchart of FIG.

  FIG. 19 is a block diagram showing the configuration of the search unit 12 in the present embodiment. The search unit 12 is chained from the element state writing unit 121 that writes changes in the element state to the element state storage unit 21, the element state reading unit 122 that reads the element state from the element state storage unit 21, and the in vivo network model DB 23. A network information acquisition unit 123 that extracts a related element relationship and writes it in the established element relationship storage unit 22; an element state change unit 124 that writes a change in the element state in the established element relationship storage unit 22; An element relationship verification unit 125 that verifies whether the element relationship is established. The element state writing unit 121 and the element state reading unit 122 constitute an element state updating unit 18, and the element state changing unit 124 and the element relationship verification unit 125 constitute a network updating unit 19.

  The element state writing unit 121 writes element data including elements and element states in the element state storage unit 21. The element state writing unit 121 operates as follows. The element data designated by the user is received from the input unit 11 (110121), and the element data is written in the element state storage unit 21 (121021). In addition, the element relation verification unit 125 receives the element data of the result element including the element whose state changes when established and the element state, the number of chains currently being searched (1250121), and writes the element data and the number of chains. Next, the number of chains currently being searched is passed to the element state reading unit 122 (1210122).

  The element state reading unit 122 reads element data including elements and element states in the chain currently being searched from the element state storage unit 21. It works as follows. The element state reading unit 122 receives the number of chains currently being searched from the element state writing unit 121 (1210122), refers to the element state storage unit 21, and reads element data based on the number of chains being searched (210122). ). This element data and the number of chains currently being searched are passed to the network information acquisition unit 123 (1220123).

  The network information acquisition unit 123 extracts the element relation related to the chain currently being searched from the in-vivo network model DB 23 and writes it in the established element relation storage unit 22. The network information acquisition unit 123 operates as follows. The element status reading unit 122 receives the element data including the element and the element status, and the number of chains currently being searched (1220123). Next, with reference to the in-vivo network model DB 23, the element relation including the received element data as a cause element in the formation condition is extracted (230123). Next, the extracted element relation is written into the established element relation storage unit 22 (1230302). Next, the received element data and the number of chains currently being searched are passed to the element state changing unit 124 (1230124).

  The element state change unit 124 writes that the element state has changed in the establishment condition column of the establishment element relationship storage unit 22. It works as follows. The element state changing unit 124 receives element data including element and element state and the number of chains currently being searched from the network information acquiring unit 123 (1230124). Next, the part corresponding to the received element data in the element relation condition column of the established element relation storage unit 22 is rewritten (124402). Next, the number of chains currently being searched is passed to the element relation verification unit 125 (1240125).

  The element relationship verification unit 125 verifies whether the element relationship is established with reference to the establishment condition of the established element relationship storage unit 22. It works as follows. The element relationship verification unit 125 receives the number of chains currently being searched from the element state change unit 124 (1240125). Next, the established element relation storage unit 22 is referred to (220125), and it is verified whether or not the element relation is established from the information on the establishment condition of each element relation. If there is an established element relationship, the number of chains currently being searched is written in the established element relationship storage unit 22 (125022), the element data of the result element consisting of the combination of the connection destination element and element state of the element relationship, and the current search The chain number is passed to the element state writing unit 121 (1250121).

  FIG. 3 is a flowchart showing the operation of the simulation system of this embodiment. The process of the search unit 12 will be described with reference to the flowchart of FIG.

  First, element data is written in the element state storage unit 21, the maximum number of chains is held, and the number of chains currently being searched is initialized (step S1). Next, the element state reading unit 122 reads element data (step S2). Next, the network information acquisition unit 123 extracts the element relation related to the element data from the in-vivo network model DB 23 and writes it in the established element relation storage unit 22 (step S3). Next, the element state changing unit 124 writes that the element of the element data or the element state has changed into the established element relation storage unit 22 (step S4).

  Next, the element relationship verification unit 125 verifies whether the element relationship in the established element relationship storage unit 22 is established, and reads a result element of the established element relationship (step S5). Next, the element state writing unit 121 writes the obtained result element in the element state storage unit 21 (step S6). Then, the number of chains currently being searched is increased (step S7). Next, if there is unread element data in the element state storage unit 21 and the number of chains currently being searched is smaller than the maximum number of chains, the process proceeds to step S2, and the chain is continuously searched. The process proceeds to S9 (step S8).

  Subsequently, the element state reading unit 122 reads unread element data if there is element data in the element state storage unit 21 (step S9). The network information acquisition unit 123 extracts the element relation related to the element data and writes it in the established element relation storage unit 22 (step S10).

  Next, each of the above steps will be described in detail.

  Step S1) First, the inputted element data is written in the element state storage unit 21, and the maximum number of chains and the number of chains currently being searched are initialized.

  The element state writing unit 121 writes the element data received from the input unit 11 (110121) to the element state storage unit 21 (121021).

  For example, when the element “A” / element state “phosphorylation”, element “B” / element state “phosphorylation”, element “I” / element state “ionization” are designated by the input unit 11 as shown in FIG. , Each is written in the element state storage unit 21, the chain number at that time is “0”, and the read attribute is empty.

  The search unit 12 initializes a variable N and a variable n. The variable N is the maximum number of chains, and if there is a maximum number of chains received from the input unit 11, it is substituted, and if not, a sufficiently large value is substituted. The variable n is the number of chains currently being searched, and “0” is substituted. For example, when the maximum number of chains “5” is received from the input unit 11, N = 5 and n = 0.

  The number n of chains currently being searched is passed to the element state reading unit 122 (1210122).

  Step S2) Next, the element state reading unit 122 reads element data that changes with the number of chains currently being searched from the element state storage unit 21.

  The element state reading unit 122 receives the number n of chains currently being searched (1210122), refers to the element state storage unit 21 and reads any unread element data of the number of chains n (210122). At this time, the fact that it has been read is written in the read attribute of the record read in the element state storage unit 21. The read element data is transferred to the network information acquisition unit 123 (1220123).

  For example, if n is “0”, element “A”, element state “phosphorylation”, element “B”, element state “phosphorylation”, element “I”, element state “ionization”, The number of chains n = 0 being searched is read, and “completed” is written in the read attribute of these records. A set of three elements and element states read, n = 0, is passed to the network information acquisition unit 123.

  Step S3) Next, the element relation related to the received element data is extracted from the in-vivo network model DB 23 and written into the established element relation storage unit 22.

  The network information acquisition unit 123 receives the element data and the number of chains currently being searched (1220123). Next, the in-vivo network model DB 23 is referred to (230123), and if there is an element relation including element data as a cause element in the formation condition, it is extracted. Next, if the extracted element relation is not written in the established element relation storage unit 22, it is written (1230302).

  For example, three element data of element “A”, element state “phosphorylation”, element “B”, element state “phosphorylation”, element “I” and element state “ionization”, the number of chains currently being searched n = Consider the case where 0 is received. Referring to the element relation table of the in-vivo network model DB 23 as shown in FIG. 2, the element relations “arc 1” and “arc 2” including the element “A” and the element state “phosphorylation” in the establishment condition, The element relation “Arc 1”, “Arc 2”, “Arc 9”, “Arc 11” including the element “B” and the element state “phosphorylation”, and the element “I” and the element state “ionization” as the formation conditions The element relation “arc 3” to be included is extracted. Next, a result element composed of a set of a relation name of the element relation, an establishment condition, an element whose state changes upon establishment and an element state upon establishment is written into the establishment element relation storage unit 22, and the establishment attribute is empty. An element whose state changes when established is a connection destination element in the element relationship.

  Here, when the element information including the element and the element state is received and the element state is “*”, the network information acquisition unit 123 extracts all the element relations including the element as a fulfillment condition. If the element is “*”, all element relationships including the element state in the establishment condition are extracted. For example, when the element “AB” and the element state “*” are received, the element relation table of the in-vivo network model DB 23 as shown in FIG. 2 is referred to, and the element relation “arc 3”, “ “Arc 4”, “Arc 5”, and “Arc 6” are extracted. As described above, even when any in-vivo element or element state is received, all element relationships that may be established can be extracted.

  Furthermore, in the element relation table of the in-vivo network model DB 23, when the element state of the establishment condition is unknown, it is handled that all the element states of the connection source element are set. If the element state at the time when the result element is established is unknown, it is handled as all element states. For example, in the case of the relation name “arc 10” in the in-vivo network model DB 23 as shown in FIG. 2, it is assumed that “F (*)” is set as the establishment condition and “*” is set as the element state when the result element is established. deal with. By processing in this way, even if the element state of the establishment condition is unknown or the element state at the time of establishment of the result element is unknown, it can be established by treating all the element states as being set. All element relationships can be extracted.

  The network information acquisition unit 123 passes the received element data and the number of chains currently being searched to the element state change unit 124 (1230124).

  Step S4) Next, the fact that the element and the element state have changed is written in the established element relation storage unit 22.

  The element state changing unit 124 receives the element data and the number of chains currently being searched (1230124). Next, the element state is changed with reference to the established element relationship storage unit 22 (124402). The element state is changed as follows. The part corresponding to the received element data is replaced with “True” in the column of the condition for all records in the established element relation storage unit 22.

  For example, three element data of element “A”, element state “phosphorylation”, element “B”, element state “phosphorylation”, element “I” and element state “ionization”, the number of chains currently being searched n = Consider the case where 0 is received. Rewrite the corresponding part of the condition “A (phosphorylation) AND B (phosphorylation)” of the element relation “arc 1” for the element “A” and the element state “phosphorylation” “True AND B (phosphorylation)” " Similarly, the element relationship “arc 2” is “B (phosphorylated) AND True”.

  Subsequently, when the corresponding part of the element “B” / element state “phosphorylation” is further rewritten, the element relation “Arc 1” is “True AND True”, the relation name “Arc 2” is “True AND True”, and the element relation “Arc 9” is “True AND D (phosphorylated)”, and the element relationship “Arc 11” is “D (phosphorylated) AND True”. Furthermore, when the corresponding portion of the element “I” and the element state “ionization” is rewritten, the element relation “arc 3” becomes “True AND AB (join)”.

  Here, when the element state change unit 124 receives element data including an element and an element state, if the element state is “*”, the element state change unit 124 sets “True” if the element corresponds to the element state, and the element indicates “*”. In this case, if the element state corresponds, “True” is set. Further, when the establishment condition of the establishment element relationship storage unit 22 is unknown, it is regarded that the establishment condition is established, and the column of the establishment condition is set to “True”.

  The element state changing unit 124 passes the chain number n currently being searched to the element relation verifying unit 125 (1240125).

  Step S5) Next, the established element relationship storage unit 22 is referenced to verify whether there is an established element relationship, and a result element of the established element relationship is read.

  The element relationship verification unit 125 receives the number n of chains currently being searched (1240125), refers to the established element relationship storage unit 22 (125022), checks whether the establishment condition is satisfied, and determines whether or not the element relationship is established. Verify that. In order to verify the establishment condition, the logical expression is evaluated by paying attention to the “True” portion of the establishment conditions in the establishment element relation storage unit 22, and if the logical expression is true, the element relation is established. If there is an established element relationship, the number n + 1 of the currently searched chain is written in the chain number attribute of the established element relation storage unit 22, “completed” is written in the established attribute, and the element that changes the state at the time of establishment and the change in the element state Read from the established element relationship storage unit 22 (220125).

  For example, the chain number n = 0 currently being searched is received. With reference to the established element relation storage unit 22, when the logical expressions of the establishment conditions of the element relation “arc 1” and the element relation “arc 2” are evaluated, if the result is true, the relation name “arc 1” and the relation name “arc” It can be seen that “2” is established. In this case, the number of chains is “1” and “completed” is written in the establishment attribute to the corresponding record in the establishment element relationship storage unit 22, and element data of the element “AB” / element state “combined” is read.

  The element relation verification unit 125 passes the element data of the result element that changes state when established, and the number of chains currently being searched to the element state writing unit 121 (1250121).

  Step S6) If there is an established result element, it is written in the element state storage unit 21.

  If there is an element relationship established in step S5, the element state writing unit 121 receives the element data of the result element and the number of chains currently being searched (1250121), and this element data is written into the element state storage unit 21. If not, it is written (121021). At this time, n + 1 is written in the chain number attribute. For example, the element “AB”, the element state “combined”, the number of chains currently being searched n = 0 is received, the element / element state and the number of chains “1” are written, and the read attribute is not written.

  Step S7) Next, the number of chains currently being searched is increased by adding 1 to the number n of chains currently being searched. For example, n = 1.

  Step S8) Next, when the number of chains currently being searched is smaller than the maximum number of chains and there is unread element data in the element state storage unit 21, the process proceeds to step S2 to search for the next chain. For example, if the maximum number of chains N is “5”, the current number of chains n is “1”, the element “AB” / element state “bound”, and the number of chains “1” is unread, the next chain is searched. To do.

  In the next chain, in step S2, unread element data of the current chain number n = 1 is read as a cause element. For example, the element “AB” and the element state “join” are read. Referring to the in-vivo network model DB 23 in FIG. 2, in step S3, the element relation “arc 3” and the element relation “arc 6” are extracted, and only the element relation “arc 6” that has not been written yet is written. In step S4, the element data of the element relation “arc 3” and the element relation “arc 6” is changed. In step S5, “arc 3” and “arc 6” are established, and two result elements of element “AB” / element state “decomposition” and element “C” / element state “expression activity” are obtained. In step S7, this result element is written.

  If the condition is not met in step S8, the process proceeds to step S9.

  Step S9) Read unread element data in the element state storage unit 21.

  The element state reading unit 122 refers to the element state storage unit 21 according to an instruction from the search unit 12 and reads unread element data regardless of the number of chains. The read element data is deleted from the element state storage unit 21.

  The search unit 12 acquires the read element data from the element state reading unit 122.

  Step S 10) Element relationships are extracted with reference to the in vivo network model DB 23, and are written in the established element relationship storage unit 22.

  The search unit 12 passes the element data including the combination of the element and the element state received in step S <b> 9 to the network information acquisition unit 123.

  The network information acquisition unit 123 receives element data from the search unit 12. Next, as in step S <b> 3, the element relation is extracted with reference to the in vivo network model DB 23 and written into the established element relation storage unit 22.

  The search unit 12 notifies the display processing unit 13 that is a component of the output unit 16 that the search has been completed (12013).

  The search unit 12 has the following features. A feature of the search unit 12 is that a plurality of element states are considered for one element.

  In the processing of the search unit 12, it is important to search for one element in consideration of a plurality of element states. This is because in an in vivo network, one in vivo element is in various element states at the same time. For example, let us consider a case where an element “AB” in which the element “A” and the element “B” are combined and an element “I” that decomposes the element “AB” are present in the living body at the same time. At this time, even if the element “I” decomposes the element “AB”, not all the elements “AB” are decomposed at a time, and the element “AB” that is connected remains.

  Therefore, the state change that occurs in a chain according to the state in which the elements “AB” are combined continues to occur. That is, the element “AB” is simultaneously in two element states of “combined” and “decomposed”. The search unit 12 performs a search in consideration of the fact that one in-vivo element simultaneously becomes a plurality of element states by searching based on element data including a pair of elements and element states in the process of searching for a chain. doing.

  Returning to FIG. 1, next, the display processing unit 13 refers to the established element relationship storage unit 22 and the element state storage unit 21 (22013, 21013), and positions of nodes and arcs for reconfiguring and displaying the network. Is created and passed to the display device 14 (13014).

  First, the display processing unit 13 creates an element relation list of the in-vivo network and an expandable element state list that is a list of element data necessary for extending the influence range. Next, the display processing unit 13 reconfigures the in-vivo network from the element relation list, and creates information such as nodes and arc positions for displaying the in-vivo network.

  First, the display processing unit 13 creates an element relation list of the in-vivo network and an expandable element state list that is a list of element data necessary for extending the influence range.

  FIG. 7 is a diagram illustrating an example of an element relation list and an expandable element state list created by the display processing unit according to the present embodiment.

  FIG. 7A is an example of an element relation list. It consists of the element name of the connection source of each element relationship, its type, its element state, element name of the connection destination, its type, element state, the number of chains established in the search process, related elements, and conditions for establishment. Here, the related element is a cause element other than the connection source element among the cause elements constituting the establishment condition.

  FIG. 7B is an example of the expandable element state list. The expandable element state list is a table showing what kind of element state is added to the element state designated by the user and the influence range is further expanded. It is composed of expandable element data, conditions for establishing element relations established thereby, connection source element names and element states, and connection destination element names and element states.

  For example, suppose that the result of the search by the search unit 12 is the formation element relationship table of FIG. If attention is paid to the conditions for establishing the element relations “Arc 9” and “Arc 11” that are not established, this element relation is established by adding the element “D” and the element state “phosphorylation” that are not “True”. It can be seen that the range of influence of the in-vivo network is widened. At this time, the element “D” and the element relationship “phosphorylation” are included in the list as expandable element data.

  The element relation list is created as follows.

  First, the display processing unit 13 reads the relationship name and chain number of the established element relationship from the established element relationship storage unit 22 (22013). Next, the in-vivo network model DB 23 is referred to via the network information acquisition unit 123 and searched using the relationship name as a key, and the connection source element name and its element state, the connection destination element name and its element state, and establishment conditions are obtained. Reading, reading the type of in-vivo element using the element name as a key (23013), and creating element relation list information.

  The connection source element state is an element state related to the connection source element in the condition for establishing the element relationship. For example, in the relation name “arc 1” in the in vivo network model DB 23 as shown in FIG. “A”, connection element state “phosphorylated”.

  Next, the display processing unit 13 adds element data that does not appear in the element relation but appears only in the element state storage unit 21 to the element relation list. The read element data is read from the element state storage unit 21 (21013). Compared with the connection source element / element state and connection destination element / element state fields of the element relation list created earlier, element data that appears only in the element state storage unit 21 is extracted. The element type is acquired from the in-vivo network model DB 23 via the network information acquisition unit 123 using the element name of the extracted element data as a key (23013). The extracted element / element state / type is set as the connection source element / element state / type, and a record in which the connection destination element, type, element state, chain number, related element, and establishment condition are empty is added to the element relation list.

  For example, when the search unit 12 receives only the element “A” and the element state “phosphorylation” from the input unit 11 and performs a search with reference to the in vivo network model DB 23 as shown in FIG. There is no. Therefore, the established element relationship storage unit 22 has no established element relationship. However, the element state storage unit 21 holds the element “A” and the element state “phosphorylation” as read. In this case, the input element “A” and element state “phosphorylation” are added to the list as no connection destination.

  The extensible element state list is created as follows.

  First, the display processing unit 13 refers to the established element relation storage unit 22 and acquires the relation name and establishment condition of the element relation that has not been established (22013). Next, paying attention to the establishment condition, a part of element data that is not “True” is extracted, and this is set as expandable element data. Next, the in-vivo network model DB 23 is referred to via the network information acquisition unit 123, and the connection source element and its element state, the connection destination element and its element state, and establishment conditions are acquired using the relation name as a key (23013). Next, information on the expandable element state list is created.

  At this time, the simulation system of the present embodiment includes an unestablished element relation storage unit that stores an unestablished element relation record in which only a part of the establishment condition or the establishment result is established in the element relation table as an unestablished element relation. Further, it may be provided.

  If such an unestablished element relationship storage unit is provided, the display processing unit 13 creates information on the expandable element state list described above by acquiring the unestablished element relationship from the unestablished element relationship storage unit. This is because it becomes easy.

  Here, the connection source element state is an element state related to the connection source element in the condition for establishing the element relation. The connection destination element state is an element state related to the connection destination element in the result of establishment of the element relation.

  Returning to FIG. 1, next, the display processing unit 13 creates information for displaying the in-vivo network according to the display method based on the element relation list, and passes the information to the display device 14 (13014).

  One display method is a method of expressing a living body element as a node, an element state as a subnode, and a network in which one record of the element relation list is an arc. Here, the display information is generated so that one sub-node exists as element data including a combination of the in-vivo element and its element state, and the arc is represented by a directed arc between the element states that are sub-nodes.

  For example, the arc of the first record of the element relation list in FIG. 7A is the sub-node “phosphorylation” of the node “A” as the connection source, the sub-node “join” of the node “AB”, and the second record , The connection source is the sub-node “phosphorylation” of the node “B”, and the connection destination is the sub-node “coupling” of the node “AB”. At this time, there is one node “AB” and one sub-node “join”, and the arc of the first record and the second record uses this sub-node as the connection destination. The node shape is changed for each type of in-vivo element, and the sub-node shape is changed for each element state for display.

  In this display method, arrangement information of each node, sub-node, and arc is created as information corresponding to the display method of the in-vivo network.

  The arrangement information is created using a conventional arrangement method such as a spring model. However, since the conventional arrangement method cannot process subnodes, the following processing is added.

  Prior to the creation of placement information by a placement method such as a conventional spring model, the relative position of each sub-node with respect to the node is determined in advance, and the arc is connected to the node. Based on only the nodes and arcs, the placement is determined by the conventional method. After the arrangement is completed, the subnode is placed at a relative position, and the connection source and connection destination of each arc are set as the subnode positions.

  As another method, before the arrangement information is created by a conventional method such as a spring model, all the subnodes are also considered as nodes, an arc is assumed between the nodes and the subnodes, and the conventional arrangement method is used. When using the placement method, the assumed arc distance is placed while adjusting so that the node and the sub-node can be seen close to each other. For example, if the node is circular, the assumed arc distance is the radius, and if the node is square, the distance from the center of gravity to the vertex is used.

  The display processing unit 13 passes the arrangement information of each node, subnode, and arc and the shape of the node and subnode to the display device 14.

  Returning to FIG. 1, next, the display device 14 acquires information for displaying the in-vivo network from the display processing unit 13, and displays the in-vivo network.

  FIG. 6 is a diagram illustrating an example in which display information regarding the in-vivo network created by the display processing unit in the present embodiment is output by the display device.

  In this example, the node shape is changed for each type of in-vivo element, and the sub-node shape is changed for each element state. For example, D1 is a node and represents an in-vivo element of the element “A”, and it can be seen from the shape that the type is protein. D2 is a sub-node and represents the element state “phosphorylation” of the element “A”. D3 is a sub-node and represents an element state “bond” of the element “AB”, D4 is an arc, and the element “A” / element state “phosphorylation” is related to the element state “bond” of the element “AB” I understand. The types of in-vivo elements may be divided by node color or node name, and element states may be divided by sub-node color or arc color.

  In this way, by displaying the connection relationship for each element state of the in vivo element, the user can easily find not only the relationship between the in vivo elements of the in vivo network but also the relationship including the conditions for establishment thereof. Can do.

  In the conventional in-vivo network display method, since the in-vivo element is a node, when the in-vivo element related to a certain in-vivo element is illustrated, the node connected to the certain node is displayed as related. . However, the in-vivo network needs a condition for establishing an element relationship in order to be in a certain element state. Further, the condition is expressed by a combination of element states of a plurality of elements. Therefore, it is important to display the connection relationship for each element state of the in-vivo element and to illustrate the establishment condition.

  In this embodiment, it is easy to find the establishment condition by displaying the element relation for each element state of the in-vivo element. For example, referring to the sub-node of D3 in FIG. 6, the relevant establishment condition for becoming the element state “binding” of the element “AB” is the element state “phosphorylation” of the elements “A” and “B”. The element state “phosphorylation” of element “I” is not relevant. Further, referring to the sub-node of D5, it can be readily understood that the establishment condition related to the element state “decomposition” is the element “I”.

  Returning to FIG. 1, the display processing unit 13 can further create a chained moving image for visually showing the establishment condition and the chain movement as another display method.

  This display method using chained animation is expressed as a network in which the elements in the living body are nodes and one record of the element relation list is an arc, each arc is displayed at the timing when the chain occurs, and the display of each arc is also visually animated This is a display method.

  First, on the basis of the element relation list, arrangement information is created by an arrangement method such as a conventional spring model using in vivo elements as nodes and element relations as arcs.

  Next, the timing for displaying the arc is obtained based on the element relation list. The element relation list is arranged in ascending order of the number of chains, and the display timing of each arc is set as the number of chains.

  Next, the arc animation table describing the animation method held in the display processing unit 13 is referred to determine the animation method for each arc.

  For example, FIG. 20 is a diagram illustrating an example of an animation image displayed on the arc animation table and display device held in the display processing unit of the present embodiment.

  Describes the element type and element state of the connection source, the element type and element state of the connection destination, and the type of animation. For example, if the element type of the connection source is “protein”, the element state is “phosphorylated”, the element type of the connection destination is “protein”, and the element state is “phosphorylated”, the first record is “animation” 1 ”. The animation 1 displays (1), (2), and (3) in order in the figure, and performs animation by describing the node name in “X”. When multiple element relationships are established in each chain, animations are displayed in an overlapping manner.

  FIG. 8 is a diagram illustrating an example of an animation created by the display processing unit in the present embodiment. It is an animation when the chain number is “1” in the element relation list of FIG. Referring to FIG. 7A, it can be seen that two arcs are displayed when the chain number is “1”. From the arc animation table of FIG. 20, it can be seen that the animation of these arcs is animation 2. When the animations of these two arcs are superimposed and displayed, the moving images are in the order of FIGS. 8 (1), (2), and (3).

  The display processing unit 13 passes this chained moving image to the display device 14, and the display device 14 displays them in order.

  Returning to FIG. 1, the display processing unit 13 can further display an element relation list and an expandable element relation list as another display method.

  The display processing unit 13 receives an instruction to display an element relation list or an expandable element list from the input unit 11 (11013). The element relation list or the expandable element list created earlier is passed to the display device 14 (13014).

  The display device 14 displays the element relation list or the expandable element list delivered from the display processing unit 13.

  Returning to FIG. 1, with the support of the user, the input unit further receives a search condition including new element data for the simulation result output from the output unit, and the search unit further searches the chain, and the search process is performed in the element state. It can be added to the storage unit and the established element relationship storage unit and displayed on the output unit. For example, the user can display how much the range of influence actually expands by selecting an element from the expandable element list and further searching based on this element data.

  Next, the effect of this embodiment will be described. In the present embodiment, the search unit is configured to be able to search for a chained state change caused by addition or update of element data. Therefore, the chained change of the element state of the in vivo element in the in vivo network is moved. It is possible to simulate the influence on the in-vivo network by performing a search.

  In the present embodiment, since the search process in the search unit is held in the element state storage unit and the established element relationship storage unit, the display processing unit uses these pieces of information to exchange the element data of the in vivo network. The establishment conditions can be displayed, and a list of element data that can be expanded can also be displayed.

<Second Embodiment>
Next, another embodiment for carrying out the invention of the present invention will be described in detail with reference to the drawings.

  FIG. 9 is a block diagram showing the configuration of the simulation system of this embodiment. In this embodiment, the search unit 12 of the first embodiment is replaced with a search unit 12A. With such a configuration, not only searching in the forward direction (downstream) but also searching in the reverse direction (upstream) is performed.

  Here, the forward search is the search method of the first embodiment, and when element data including a combination of an element and an element state is input, the cause element included in the condition for establishing the element relation is considered. Then, the established element relation is extracted, and further, the result element including the set of the element after the state change and the element state occurring as a result is sequentially searched.

  On the other hand, in the reverse search, when element data is input, the element relation result element is considered, the element relation that becomes the input element data as a result of the element relation being established is searched and specified by the condition The search is performed sequentially based on the cause element including the pair of the current element and the element state. That is, the reverse search searches for the input element and the causal element that is in the element state.

  In addition to the plurality of element data from the input unit 11, the search unit 12A further receives an instruction whether to perform a forward search or whether to perform a reverse search (11012). Then, according to the instruction content, the in vivo network model DB 23 is referred to (23012), and not only the cause element included in the element condition but also the result element is considered, and the reverse search is performed.

  The search in the reverse direction is performed as follows, referring to the in-vivo network model DB 23, and extracting an element relationship using the received element data as a result element after the state change. If extraction is possible, a cause element that is element data necessary for establishment is acquired based on the conditions for establishment of the extracted element relation.

  This cause element is further assumed as a result element, and further search is performed, and the search is sequentially performed until there is no element relation that can be extracted. The search unit 12A holds the search process in the established element relationship storage unit 22 and the element state storage unit 21 (12022, 12023).

  By adopting such a configuration, it becomes possible to search not only the influence due to the element state but also the in-vivo element that causes the element state and the element state.

  Next, the overall operation in the present embodiment will be described in detail with reference to FIG.

  This embodiment is different from the first embodiment in that the search unit 12 is replaced with a search unit 12A.

  FIG. 10 is a flowchart showing the operation of the simulation system of this embodiment. FIG. 21 is a block diagram showing the configuration of the search unit in this embodiment.

  The operation of the search unit 12A will be described in detail with reference to the block diagram of FIG. 21 and the flowchart of FIG. The search unit 12A of the present embodiment is different from the search unit 12 in that the network information acquisition unit 123 is replaced with another network information acquisition unit 126.

  This network information acquisition unit 126 extracts element relationships related to the chain currently being searched from the in vivo network model DB 23 in consideration of not only the cause element included in the establishment condition but also the result element included in the establishment result. Then, it is written in the formation element relationship storage unit 22.

  The network information acquisition unit 126 operates as follows. The search unit 12A receives an instruction indicating whether the search is forward search or reverse search, and receives element data and the number of chains currently being searched from the element state reading unit 122 (1220126). Next, in the case of forward search, processing similar to that performed by the network information acquisition unit 123 is performed. In the reverse search, the result element of the in-vivo network model DB 23 is referred to, and the element relation using the received element data as the result element is extracted (230126).

  Next, the extracted element relation is written into the established element relation storage unit 22 (126022). Next, element data (cause element) necessary for establishment is extracted from the conditions for establishment of the extracted element relation. The extracted element data and the number of chains currently being searched are passed to the element state writing unit 121 (1260121). The search unit 12A controls which of the forward search and the reverse search is used.

  Further, the operation of the search unit 12A will be described in detail with reference to the flowchart of FIG.

  Step 21) First, element data, whether to search in the forward direction or in the reverse direction, is obtained from the input unit 11, or the maximum number of chains is obtained. The received element data is written in the element state storage unit 21, and the maximum number of chains and the number of chains currently being searched are initialized.

  FIG. 11 is a diagram illustrating an example of a screen for obtaining information specified by the input unit in the present embodiment.

  The input unit 11 receives a user designation through such a graphical user interface, for example. In addition to the first embodiment, it is possible to select whether to perform a forward chain search or a backward chain search. Through such a screen, the element / element state pair, the maximum number of chains, whether to perform forward chaining, and whether to perform backward chaining search are acquired. This screen is an example, and the maximum number of chains may be input separately for forward search and reverse search.

  Returning to FIG. 10, the element state writing unit 121 writes the received element data in the element state storage unit 21 as in step S <b> 1. Further, similarly to step S1, a variable N representing the maximum number of chains and a number n of chains currently being searched are initialized.

  Step S22) Next, the search unit 12A determines whether or not to perform a forward search. If the forward search is to be performed, the process proceeds to step S23. If not, the process proceeds to step S24.

  Step S23) As shown in the flowchart of FIG. 3, the same process as the search process 1 of the search unit 12 of the first embodiment is performed. Thereby, a forward search is performed.

  Step S24) It is determined whether or not the search unit 12A performs a reverse search. If searching in the reverse direction is performed, the process proceeds to step S25.

  Step S25) The search unit 12A performs initialization for searching in the reverse direction.

  The search unit 12A sets N as the maximum number of chains in the reverse search, and 0 as the number of chains currently being searched. Further, the search unit 12A sets the record of the chain number 0 in the element state storage unit 21 to be unread. For example, in the case of the input as shown in FIG. 11, N = 5, n = 0, element “A” / element state “phosphorylated”, element “B” / element state “phosphorylated”, element in the element state storage unit 21 The record of “I” / element state “ionization” is made unread.

  Step S26) Next, as in step S2, the element state reading unit 122 reads element data that changes depending on the number of chains currently being searched from the element state storage unit 21.

  The read element data and the number of chains currently being searched are passed to the network information acquisition unit 126.

  Step S27) Next, the network information acquisition unit 126 extracts related element relationships from the in-vivo network model DB 23.

  The network information acquisition unit 126 receives element data including a set of elements and element states, and the number of chains currently being searched (1220126). Next, the in-vivo network model DB 23 is referred to (230126), and element relationships in which the read element data is a result element including a set of a connection destination element and its element state are extracted.

  Next, if the extracted element relation is not written in the established element relation storage unit 22, the extracted element relation is written, and the established attribute is set to “completed”. If written, the formation attribute of the corresponding record is set to “completed” (126022).

  Here, when the element information is received and the element state is “*”, the network information acquisition unit 126 extracts all element relationships having the element as a connection destination element. If the element is “*”, all element relationships having the element state as a result element are extracted. Furthermore, in the element relation table of the in-vivo network model DB 23, when the establishment condition is unknown, it is handled that all the element states of the connection source element are set. Further, when the element state of the result element included in the establishment result is unknown, it is treated as if all element states are set.

  Step S28) Next, the network information acquisition unit 126 refers to the extracted condition for establishing the element relation, and extracts element data (cause element) including a set of elements and element states necessary for establishing the element relation.

  This network information acquisition unit 126 refers to the element relation establishment condition extracted in step S27, and extracts element data of the cause element necessary for establishment. For example, if the establishment condition is “D (phosphorylation) AND B (phosphorylation)”, two causal elements of element “D”, element state “phosphorylation”, element “B” and element state “phosphorylation” Extract element data of. Further, when the element state is not specified in the fulfillment condition, the specified element is treated as a connection source element, and the element state is treated as all element states.

  The extracted element data and the number of chains currently being searched are passed to the element state writing unit 121.

  Step S29) The element state writing unit 121 writes the extracted element data into the element state storage unit 21.

  The element state writing unit 121 receives the element data and the number of chains currently being searched (step 1260121), and writes them to the element state storage unit 21, as in step S6. However, the number of chains at the time of writing is n-1, and when the number of chains is 0 or less and the same element data is already written, the number is not written.

  Step S210) Next, the number of chains currently being searched is reduced by subtracting 1 from the number n of chains currently being searched. For example, n = −1.

  Step S211) Next, when the absolute value of the number n of chains currently being searched is smaller than the maximum number of chains and there is an unread record in the element state storage unit 21, the next chain is searched. Otherwise, the process proceeds to step S212.

  Step S212) Next, the element state reading unit 122 refers to the element state storage unit 21 in accordance with an instruction from the search unit 12A, and extracts all element data and reading attributes of the record having a negative chain number.

  However, when unread element data is read, the record is deleted from the element state storage unit 21.

  The extracted element data and read attributes are passed to the search unit 12A.

  Step S213) Next, the element state changing unit 124 changes the element data in accordance with an instruction from the searching unit 12A.

  Of the element data received in step S212, the search unit 12A passes the element data whose read attribute has been read to the element state change unit.

  The element state change unit 124 receives element data from the search unit 12 </ b> A and changes the element data in the established element relationship storage unit 22. The changing method is the same as in the first embodiment. The reverse search is performed here because the element data is not changed.

  Step S214) Next, the network information acquisition unit 126 performs the same processing as Step S10 of the first embodiment in accordance with an instruction from the search unit 12A, and writes the element relationship in the established element relationship storage unit 22.

  The search unit 12A passes all the element data received in step S212 to the network information acquisition unit 126.

  The network information acquisition unit 126 receives the element / element state from the search unit 12A, extracts the element relationship with reference to the in-vivo network model DB 23, as in step S10 of the first embodiment, and the established element relationship storage unit 22 Write to.

  The search unit 12A notifies the display processing unit 13 that is a component of the output unit 17 that the search has been completed (12013).

  The effect of this embodiment will be described. In the present embodiment for carrying out the present invention, since the search unit is configured to perform a reverse search, a simulation for searching the cause of the input element data using the in vivo network is performed. Can do.

<Third Embodiment>
Next, a third embodiment of the present invention will be described in detail with reference to the drawings.

  FIG. 12 is a block diagram showing the configuration of the simulation system of this embodiment.

  Referring to FIG. 12, the simulation system according to the present embodiment is different from the simulation system according to the second embodiment in that an experiment result DB 31 of an external database, an experiment result correspondence unit 15, and an experiment result correspondence storage unit 24 are added. Yes.

  FIG. 13 is a diagram showing an example of an experiment result database in the present embodiment. The experiment result DB 31 stores a plurality of experiment results associated with experiment types and experiment names. FIG. 13 shows the experimental results of the experiment type “DNA microarray” and the experiment name “experiment 1”. The experimental result is composed of a plurality of elements and experimental result values. For example, in the first record, the value of the experimental result of the element “x” is “0.4”. This is an example, and other experimental types such as electrophoresis may be included, and information such as element types may be included. Note that experimental conditions may be used instead of experimental types. This is because the interpretation of the value of the experimental result can be changed if the experimental condition is different even for the same experimental type.

  FIG. 14 is a diagram illustrating an example of an experiment result correspondence storage unit in the present embodiment. The experimental result correspondence storage unit 24 stores experimental data including element data, experimental types (or experimental conditions), and experimental result values associated with each other.

  For example, the first record indicates that if the experiment type is “DNA microarray” and the experimental value is an element of 0.5 or less, the element state corresponds to “expression suppression”.

  The experiment result handling unit 15 receives, from the input unit 11, whether to perform a forward search or a reverse search, or to specify the maximum number of chains, and an experiment type and a set of experiment results (11015). Next, the experiment result correspondence storage unit 24 is referred to (24015), and the element state corresponding to this is obtained from the value of the experiment result of each element. Next, the obtained element data, an instruction on whether to perform a forward search or a reverse search, and the maximum number of chains are passed to an element state update unit included in the search unit 12A (15012).

  In addition, although this experiment result corresponding | compatible part 15 may be provided separately from the element state update part contained in 12 A of search parts, it is good also as a one part block of this element state update part.

  That is, the element state updating unit acquires a combination of one or more experimental conditions and experimental results in response to a user request, creates element data associated with the combination from the experimental result correspondence storage unit 24, and The element data of the in-vivo network stored in the state storage unit 21 may be added or updated.

  In any of the above-described configurations, when an experiment type (or experiment condition) and an experiment result are input, a chained influence caused by a corresponding set of in-vivo elements and element states or In addition, it is possible to perform a simulation for searching for a set of in-vivo elements that cause the experiment results and combinations of the element states in the experiment type.

  Next, the overall operation in the present embodiment will be described in detail with reference to FIG.

  This embodiment is different from the second embodiment in that an experiment result DB 31, an experiment result correspondence unit 15, and an experiment result correspondence storage unit 24 are added.

  First, the input unit 11 receives the experiment type and experiment name designated by the user, designation of the forward or reverse direction, designation of the maximum chain number, refers to the experiment result DB 31, and is associated with the experiment type and experiment name. A table of experimental results is acquired and passed to the experimental result handling unit 15 (11015).

  Next, the experiment result correspondence unit 15 refers to the experiment result correspondence storage unit 24 (24015), and obtains associated element data based on the experiment type (or experiment condition) and the experiment value of each element. For example, when the experimental result correspondence unit 15 refers to the experimental result table of FIG. 13 stored in the experimental result correspondence storage unit 24, the element “C” has the experimental value “2.6”, and the element state is “expression”. Corresponds to "activity". The element “D” has an experimental value of “0.6”, and this element state is unknown.

  Next, the experiment result handling unit 15 passes the element data whose element state is unknown, the designation of forward or reverse direction, and the maximum chain number to the search unit 12A (15012).

  Next, the search unit 12A searches the in vivo network in a chained manner by performing step S21 and subsequent steps in the second embodiment.

  The effect of this embodiment will be described. In the present embodiment for carrying out the present invention, a set of in vivo elements and element states corresponding to a set of input experiment types (or experiment conditions) and experiment results can be obtained and searched. . Therefore, when an experiment type (or experiment condition) and an experiment result are input, it is possible to perform a simulation for grasping a chain effect on the in-vivo network caused by the combination of the experiment type and the experiment result. Alternatively, it is possible to perform a simulation for retrieving a set of in-vivo elements and element states that are the cause of the combination of the experiment type and the experiment result.

<Fourth embodiment>
Next, a fourth embodiment of the present invention will be described in detail with reference to the drawings.

  FIG. 15 is a block diagram showing a configuration of the in-vivo network simulation system in the present embodiment.

  Referring to FIG. 15, the simulation system of the present embodiment has a configuration in which a path search unit 16 and a path search storage unit 25 are added to the simulation system of the second embodiment.

  The path search unit 16 searches the input unit 11 for start element data including a start in vivo element / element state, end element data including an end in vivo element / element state, and a number of paths from the shortest or longest. An instruction on whether to do so is received (11016), and the in vivo network model DB 23 is referred to via the network information acquisition unit 126 (23016), and a path connecting start element data and end element data is searched. The path search unit 16 holds the search result in the path search storage unit 25 (16025). Next, a set of all in-vivo elements and element states existing on the path, a designation for performing a forward or reverse search, and the maximum chain number “1” are passed to the search unit 12A (16012).

  The path search storage unit 25 holds search results obtained by the path search unit 16. FIG. 17 is a diagram illustrating an example of a path search storage unit in the present embodiment. The path search storage unit has a path search result table, and holds a path having a combination of an element and an element state as a node.

  By configuring in this way, it is searched whether two or more element data are influencing each other, and further, what is the set of in vivo elements and element states related to the influence when they are influencing? Simulation can be performed.

  Next, referring to FIG. 15, the overall operation in the present embodiment will be described in detail.

  The simulation system of the present embodiment is different from the simulation system of the second embodiment in that the path search unit 16 and the path search storage unit 25 are added.

  First, from the user, the input unit 11 receives start element data including an in vivo element / element state to be started, end element data including an in vivo element / element state to be ended, the number of search result paths, forward direction and reverse Get the maximum number of chains, whether to search for directions.

  FIG. 16 is a diagram illustrating an example of a screen for obtaining information specified by the input unit in the present embodiment.

  The input unit 11 receives a user's designation through, for example, a graphical user interface as shown in FIG. The graphical user interface of FIG. 16 specifies a set of start and end elements and element states. Also, the number of paths to be displayed as a search result from the longest path or the shortest path is designated. Here, the start element “B”, element state “*”, end element “H”, element state “*”, and the number of result paths are designated to be displayed from the shortest path to “5”. In the figure, there is no place for specifying whether or not to search in the forward direction or the reverse direction, and there is no place for specifying the maximum number of chains, but these may be included.

  Next, the path search unit 16 receives, from the input unit 11, the in-vivo element / element state to be started, the in-vivo element / element state to be ended, the number of paths from the shortest or longest, and the order if specified. Whether the search in the direction or the reverse direction is performed, the maximum number of chains is received (11016).

  Next, the path search unit 16 refers to the in-vivo network model DB 23 (23016) and performs path search.

  At this time, a node for path search is element data including a combination of an element and an element state, and an arc has an element relation. The arc connection source node corresponds to the connection source element and the element state in the establishment condition, and the arc connection destination node corresponds to the connection destination element included in the result element and the element state related to the connection destination element. Node.

  For example, the relation name “arc 2” in the in-vivo network model DB 23 in FIG. 2 has a connection source node of element “B” / element state “phosphorylation” and a connection destination node of element “AB” / element state “coupled”. ”. As the path search method, a conventional method such as height-first search or width-first search is used.

  However, in the conventional path search method, when the start or end element or element state is “*” indicating all elements or element states, the following preprocessing is performed.

  When the received element is “*”, the in-vivo network model DB 23 is referred to, and all nodes including the element state associated with the received element are set as start or end nodes. If the received element state is “*”, all nodes including the element associated with the received element state are set as start or end nodes. When there are a plurality of start nodes and end nodes, a path having the respective combinations as start nodes and end nodes is searched.

  For example, when element “B” / element state “*” is received at the start and element “H” / element state “*” is received at the end node, referring to the in vivo network model DB 23 of FIG. “B” —the element state “phosphorylation” and two nodes corresponding to the element “B” —the element state “inactive”, and the end node is the node of the element “H” —the element state “expression active” I understand that. Path with start node as element “B”, element state “phosphorylation”, end node as element “H”, element state “expression active”, start node as element “B”, element state “inactive”, end The node is searched for two paths of element “H” and element state “expression activity”.

  When a path having the element “B” / element state “phosphorylation” as the start node and the element “H” / element state “expression activity” as the end node is searched with reference to the in vivo network model DB 23 of FIG. The path is found. “B (phosphorylation) → BD (binding) → G (expression activity) → H (expression activity)”, “B (phosphorylation) → AB (binding) → C (expression activity) → D (expression activity) → BD (Binding) → G (expression activity) → H (expression activity) ”. There is no path in which the start node is element “B” / element state “inactivated” and the end node is element “H” / element state “expression active”.

  Next, the path search unit 16 sorts the plurality of search results by their lengths, and holds the number of the shortest or longest path received from the input unit 11 in the path search storage unit 25 (16025). ).

  Next, the path search unit 16 extracts the element data existing on the path of the path search result, and searches for the element data, an instruction for the forward search or the reverse search, and designation of the maximum chain number. It is passed to the part 12A (16012). If the input unit has not received an instruction as to whether to search in the forward direction or the reverse direction and the designation of the maximum number of chains, a specified value is set. For example, by setting the maximum number of chains to 1 in the reverse search, it is possible to search for the cause and establishment condition of the element state.

  Next, the search unit 12A searches the chain by the element / element state pair received from the path search unit 16, the forward or reverse search, and the maximum number of chains. The search result is held in the element state storage unit 21 and the established element relationship storage unit 22.

  Next, in addition to the display method of the first embodiment so far, the display processing unit 13 performs display together with the path search result.

  FIG. 18 is a diagram illustrating an example of a path search result display in the present embodiment.

  The display processing unit 13 refers to the path search storage unit 25 together with the in-vivo network, and displays a list of path search results. The path search result list displays one path as one record. When one of the records in the path search result list is selected, a pair of element relation and element / element state corresponding to this is highlighted. Further, the element / element state pair existing in the formation condition is highlighted with reference to the formation condition of each element relation.

  The effect of this embodiment will be described. In this embodiment, the path search unit searches for paths of two in-vivo elements, holds the results, and further searches the cause data (cause elements) or the affected element data (result elements) from the results. It is configured as follows. Therefore, it is possible to perform a simulation to search whether a certain in vivo element has an influence on another in vivo element, and further, what is an in vivo element related to the in vivo element.

  As mentioned above, although the structure of this invention was demonstrated, what combined these structures arbitrarily is effective as an aspect of this invention. In addition, the expression of the present invention is converted into another category, such as an information search device that searches for a state change of an in vivo element that occurs in a chain in the in vivo network, or a program for realizing the information search device on a computer. Those are also effective as an embodiment of the present invention.

  For example, in the above embodiment, as the in vivo network model DB 23, a molecular biology database provided by the Human Genome Center, the University of Tokyo Institute of Medical Science is used. For example, a database uniquely constructed by the user is used. It may be used, and the following major databases on molecular biology shown below may be used.

DNA All nucleotide sequences (GenBank + EMBL + DDBJ)
Protein all amino acid sequences (SwissProt + PIR + PRF + PDBSTR)
nr-nt base sequence without duplication (created from GenBank, EMBL)
Amino acid sequence excluding nr-aa duplication (created from SwissProt, PIR, PRF, GenPept)
GenBank Nucleotide Sequence (including DDBJ) US NCBI, National Institute of Genetics
EMBL Nucleotide sequence European EBI
SwissProt protein amino acid sequence University of Geneva, EBI
PIR protein amino acid sequence Georgetown University (USA)
PRF protein amino acid sequence protein research promotion society
Three-dimensional structure of PDB protein Brookhaven National Laboratory
PDBSTR PDB amino acid sequence Institute for Chemical Research, Kyoto University
EPD Eukaryotic Promoter Swiss Cancer Institute
TRANSFAC transcription factor German Institute for Biotechnology
PROSITE protein sequence motif University of Geneva
LIGAND Enzyme Reaction Compound Institute for Chemical Research, Kyoto University
PATHWAY Metabolic Pathway Kyoto University
PMD mutant protein National Institute of Genetics
AAindex Amino Acid Index Institute for Chemical Research, Kyoto University
LITDB Protein Related Literature Protein Research Promotion Committee
OMIM genetic disease Johns Hopkins University
LinkDB Link information database Institute for Chemical Research, Kyoto University
Medline Medical and Biological Literature National Library of Medicine (NLM)
By using these various molecular biology databases, there is an advantage that simulation of in vivo networks including combinations of various types of in vivo elements and element states can be performed. In addition, since the contents of many of these molecular biology databases are continuously updated every day, there is an advantage that simulation can always be performed using the latest in vivo network.

It is a block diagram which shows the structure of the in-vivo network simulation system in one Embodiment of this invention. It is a figure which shows an example of the in-vivo network model database in one Embodiment of this invention. It is a flowchart figure which shows operation | movement of the simulation system of one Embodiment of this invention. It is a figure which shows an example of the element state memory | storage part and the formation element relationship memory | storage part in one Embodiment of this invention. It is a figure which shows an example of the screen for obtaining the information designated from the input part in one Embodiment of this invention. It is a figure which shows an example which output the display information regarding the in-vivo network produced with the display process part in one Embodiment of this invention with the display apparatus. It is a figure which shows an example of the element relation list | wrist produced by the display process part in one Embodiment of this invention, and an expandable element state list | wrist. It is a figure which shows an example of the animation produced in the display process part in one Embodiment of this invention. It is a block diagram which shows the structure of the in-vivo network simulation system in one Embodiment of this invention. It is a flowchart figure which shows operation | movement of the simulation system of one Embodiment of this invention. In one Embodiment of this invention, it is a figure which shows an example of the screen for obtaining the information designated from the input part. It is a block diagram which shows the structure of the simulation system of one Embodiment of this invention. It is a figure which shows an example of the experiment result database in one Embodiment of this invention. It is a figure which shows an example of the test result corresponding | compatible memory | storage part in one Embodiment of this invention. It is a block diagram which shows the structure of the in-vivo network simulation system in one Embodiment of this invention. In one Embodiment of this invention, it is a figure which shows an example of the screen for obtaining the information designated from the input part. It is a figure which shows an example of the path search memory | storage part in one Embodiment of this invention. It is a figure which shows an example of the path search result display in one Embodiment of this invention. It is the block diagram which showed the structure of the search part in one Embodiment of this invention. It is a figure which shows an example of the animation image displayed with the arc animation table produced by the display process part of one Embodiment of this invention, and a display apparatus. It is a block diagram which shows the structure of the search part in one Embodiment of this invention.

Explanation of symbols

DESCRIPTION OF SYMBOLS 10 In vivo network simulation system 11 Input part 12 Search part 12A Search part 13 Display processing part 14 Display apparatus 15 Experiment result response part 16 Path search part 31 Experiment result database 17 Output part 18 Element state update part 19 Network update part 21 Element state Storage unit 22 Established element relationship storage unit 23 In vivo network model database 24 Test result correspondence storage unit 25 Path search storage unit 27 Network information storage unit 121 Element state writing unit 122 Element state reading unit 123 Network information acquisition unit 124 Element state change Part 125 element relation verification part 126 network information acquisition part

Claims (19)

A living body including a plurality of in-vivo elements and describing the relation between the in-vivo elements by an element relation represented by a state change between the in-vivo elements, a cause element before the state change, and a result element after the state change. A simulation system that analyzes an in-vivo network model and analyzes how an element relationship between in vivo elements changes when the state of any in vivo element changes.
Obtaining the in-vivo network model having a plurality of element data including in-vivo elements and element states of the in-vivo elements, adding or updating the element data according to a user request, and updating the element data In consideration, a simulation system comprising a search unit for reconstructing the in-vivo network. A living body including a plurality of in-vivo elements and describing the relation between the in-vivo elements by an element relation represented by a state change between the in-vivo elements, a cause element before the state change, and a result element after the state change. A simulation system that analyzes an in-vivo network model and analyzes how an element relationship between in vivo elements changes when the state of any in vivo element changes.
A network information acquisition unit for acquiring the in vivo network model having a plurality of element data including a name of an in vivo element and an element state representing a chemical state or a physical state of the in vivo element;
An element state update unit that adds or updates one or more of the element data in response to a user request;
A network update unit that sequentially updates the element data included in the in vivo network in consideration of the update of the element state by the element state update unit,
An output unit for presenting information on the reconstructed in vivo network model to the user;
A simulation system comprising: The system according to claim 2, wherein the network update unit includes:
It is configured to sequentially execute an operation of generating a new element relation using the added or updated element data as a cause element and adding element data corresponding to a result element of the element relation to the in vivo network. A simulation system characterized by that. The system of claim 3, wherein
An element table for storing element data;
An element relation table including an establishment condition specified by element data of one or more cause elements, and element data of a result element generated when the establishment condition is satisfied;
Further comprising
The network update unit refers to the element relation table,
Extracting element data constituting the establishment condition from the in vivo network model,
Generate element data of the result element corresponding to the extracted cause element,
A simulation system configured to sequentially execute an operation of adding generated element data to the in-vivo network. 5. The system according to claim 2, wherein the network update unit includes:
It is configured to sequentially execute an operation of generating a new element relationship using the added or updated element data as a result element and adding element data corresponding to a cause element of the element relationship to the in-vivo network. A simulation system characterized by that. The system of claim 5, wherein
An element table for storing element data;
An element relation table including an establishment result specified by element data of one or more result elements and element data of a cause element that causes the establishment result to be generated;
Further comprising
The network update unit refers to the element relation table,
Extracting element data constituting the establishment result from the in vivo network model,
Generate element data of the cause element corresponding to the extracted result element,
A simulation system configured to sequentially execute an operation of adding generated element data to the in-vivo network. The system according to any one of claims 2 to 6,
The element state update unit adds or updates two or more element data according to the user's request,
The network update unit sequentially updates the element data included in the in-vivo network in consideration of the update of the element state by the element state update unit, and connects the two or more element data in the in-vivo network A simulation system characterized in that the system is configured to be reconstructed. The system according to any one of claims 2 to 7,
A simulation system further comprising an element data storage unit that sequentially stores addition or update of the element data as a change process of an in vivo element. The system according to any one of claims 2 to 8,
A simulation system, further comprising: an established element relation storage unit that sequentially stores element relation records in which the establishment condition or the establishment result is established in the element relation table as an element relation establishment process. The system of claim 9, wherein
A simulation system, further comprising: an unestablished element relation storage unit that stores, as an unestablished element relation, an unestablished element relation record in which only a part of the establishment condition or the establishment result is established in the element relation table. The system according to any one of claims 2 to 10,
The simulation system is configured to allow one or more different element data having only one of the names or element states of the in-vivo element to be the same as the element data. The system according to any one of claims 2 to 11,
The in vivo element includes one or more in vivo elements selected from the group consisting of genes, DNA, RNA, proteins, low molecular compounds, ions, and complexes thereof,
The element states include phosphorylation, ionization, GTP binding, GDP binding, dephosphorylation, activation, inactivation, expression activation, expression suppression, binding, degradation, transcription, translation, subcellular localization, A simulation system comprising one or more element states selected from the group consisting of in vivo tissue names, environmental conditions, and composite conditions thereof. The system according to any one of claims 2 to 12, wherein the output unit includes:
The change process of the element data stored in the element data storage unit is acquired, the formation process of the element relationship stored in the formation element relationship storage unit is acquired, and the one added or updated according to the request of the user A simulation system configured to create a simulation result representing the influence of the above element data and present it to the user. 14. The system according to claim 13, wherein the output unit includes:
A simulation representing a range that may be affected by one or more of the element data added or updated in response to a request from the user by acquiring an incomplete relation of the element relation stored in the non-established element relation storage unit A simulation system configured to further create a result and present the result to the user. The system according to claim 13 or 14, wherein the output unit includes:
A simulation system configured to create and present the simulation result as an animation in a display order associated with an establishment order of the establishment process of the element relation. The system according to any one of claims 2 to 15,
An experimental result correspondence storage unit for storing experimental data including element data, experimental conditions, and experimental results associated with each other;
The element state update unit acquires a combination of one or more experimental conditions and experimental results in response to a user request, acquires element data associated with the combination from the experimental result correspondence storage unit, A simulation system configured to add or update element data. A living body including a plurality of in-vivo elements and describing the relation between the in-vivo elements by an element relation represented by a state change between the in-vivo elements, a cause element before the state change, and a result element after the state change. A display system for displaying an in-vivo network model,
A cause element and a result element composed of element data including a name of an in vivo element and an element state representing a chemical state or a physical state of the in vivo element;
An establishment condition consisting of one or more element data for establishing the element relationship;
A display system comprising an output unit that associates and displays as an element relationship. A living body including a plurality of in-vivo elements and describing the relation between the in-vivo elements by an element relation represented by a state change between the in-vivo elements, a cause element before the state change, and a result element after the state change. A database that stores in-vivo network models,
An element table for storing element data;
An element relation table including an establishment condition specified by element data of one or more cause elements, and element data of a result element generated when the establishment condition is satisfied;
A database characterized by comprising. The computer includes a plurality of in-vivo elements, and the relationship between the in-vivo elements is represented by an element relationship represented by a state change between the in-vivo elements, a cause element before the state change, and a result element after the state change. A program for analyzing the in vivo network model described, and analyzing how the element relationship between in vivo elements changes when the state of any in vivo element changes,
The computer,
Network information acquisition means for acquiring the in-vivo network model having a plurality of element data including a name of an in-vivo element and an element state representing a chemical state or a physical state of the in-vivo element;
Element state updating means for adding or updating one or more of the element data in response to a user request;
Network update means for sequentially updating the element data included in the in vivo network in consideration of the update of the element state by the element state update unit,
Output means for presenting information about the reconstructed in vivo network model to the user;
A program characterized by functioning as

Images