Patent Publication Number: US-2023143768-A1

Title: System for determining material to be proposed to user

Description:
INCORPORATION BY REFERENCE 
     This application claims priority to Japanese Patent Application No. 2020 080755 filed on Apr. 30, 2020, the contents of which are incorporated herein by reference. 
     TECHNICAL FIELD 
     The present invention relates to a system for determining a material to be proposed to a user. 
     BACKGROUND ART 
     A virtual screening method is used for a new material searching task. In the virtual screening, a machine learning model is applied to data of a known compound, and a physical property value estimation model having a descriptor of the compound as an input is configured. The physical property value estimation model is applied to the newly generated chemical formula, and screening is performed based on the calculated estimated value. As a result, a new compound candidate that matches the purpose of the user can be presented. 
     Another related art of the present specification is Japanese Patent Laid-open Publication No. 2014-92930. This document discloses that “the information providing device  101  acquires a compound name of a target compound. The information providing device  101  searches the database  110  for a chemical formula candidate corresponding to the acquired compound name of the target compound. The information providing device  101  extracts a character string representing a substituent of the target compound from the compound name of the target compound. The information providing device  101  specifies a bonding position of a substituent bonded to a mother nucleus of a compound having a compound name including a character string representing an extracted substituent among a group of compound names stored in the database  110  in association with chemical formula candidates, thereby calculating the number of variations of the bonding position of the substituent. The information providing device  101  outputs the calculated number of variations of bonding position of the substituent in association with the chemical formula candidate.” (Abstract) 
     CITATION LIST 
     Patent Literature 
     PTL 1: JP 2014-92930 A 
     SUMMARY OF INVENTION 
     Technical Problem 
     In a case where compound candidates presented only by the physical property value estimation result are selected in the virtual screening, there is a case where they are unavailable to the user. The compound unavailable to the user is, for example, a compound that cannot be synthesized or is not practical to the user from the standpoint of cost, yield, stability, or the like. Such compounds should be excluded from the candidates of the compound to be presented. On the other hand, a compound similar to an unavailable compound may have an extremely excellent physical property value. 
     JP 2014-92930 A discloses that a candidate of a structural formula is created from a compound name and presented to a user, but does not disclose presenting a new compound desirable to the user. Therefore, a technology capable of more appropriately presenting a compound candidate desired by the user is desired. 
     Solution to Problem 
     One aspect of the present invention is a system for determining a material to be proposed to a user, the system including one or more processors; and one or more storage devices that store a program executed by the one or more processors. The one or more processors calculate an availability evaluation value indicating availability for a user of each of the plurality of materials based on a chemical formula of each of the plurality of materials. The one or more processors estimate a physical property value of each of the plurality of materials based on a chemical formula of each of the plurality of materials. The one or more processors calculate a physical property evaluation value of each of the plurality of materials based on an estimation result of the physical property value of each of the plurality of materials. The one or more processors calculate an overlooking risk evaluation value indicating priority of presenting each of the plurality of materials to the user based on the availability evaluation value and the physical property evaluation value of each of the plurality of materials. The one or more processors select a material to be presented as a candidate material from the plurality of materials according to the overlooking risk evaluation value. 
     Advantageous Effects of Invention 
     According to one aspect of the present invention, a compound candidate desired by a user can be more appropriately presented. 
    
    
     
       BRIEF DESCRIPTION OF DRAWINGS 
         FIG.  1    illustrates an example of a configuration of an experimental design support system that supports an experimental design of a compound (material) to be newly synthesized according to a first embodiment. 
         FIG.  2    illustrates a hardware configuration example of an experimental design support device and a client computer. 
         FIG.  3    illustrates a configuration example of an experimental database. 
         FIG.  4    illustrates a configuration example of an availability database. 
         FIG.  5    illustrates a process of presenting an experimental candidate compound for the first time. 
         FIG.  6    illustrates second and subsequent experimental candidate compound presenting processes. 
         FIG.  7    illustrates a flowchart of an example of a first experimental candidate compound presenting process. 
         FIG.  8    illustrates an example of a candidate presentation request input screen displayed on a monitor of a client computer by a candidate compound display unit. 
         FIG.  9    illustrates a configuration example of a candidate presentation request. 
         FIG.  10    schematically illustrates processes of generation of a candidate compound, estimation of physical property values of the candidate compound, and selection of a compound to be presented from the candidate compound. 
         FIG.  11    illustrates a flowchart of an example of second and subsequent experimental candidate compound presenting processes. 
         FIG.  12    illustrates an example of a candidate addition request input screen displayed on the monitor of the client computer by the candidate compound display unit. 
         FIG.  13    illustrates a configuration example of a candidate addition request. 
         FIG.  14    is a flowchart of an example of a candidate compound selecting process based on user feedback. 
         FIG.  15    illustrates a configuration example of a candidate addition request according to a second embodiment. 
         FIG.  16    illustrates a configuration example of an availability database according to the second embodiment. 
         FIG.  17    is a flowchart of an example of a candidate compound selecting process based on user feedback according to the second embodiment. 
     
    
    
     DESCRIPTION OF EMBODIMENTS 
     In the following description, when it is necessary for the sake of convenience, the description will be divided into a plurality of sections or embodiments, but unless otherwise specified, the sections or examples are not unrelated to each other, and one is in a relationship of some or all modified examples, details, supplementary explanations, and the like of the other. Furthermore, in the following, when referring to the number of elements and the like (including number, numerical value, amount, range, etc.), the number of elements is not limited to a specific number unless otherwise stated or unless clearly limited to the specific number in principle, and the number of elements may be greater than or equal to or less than or equal to the specific number. 
     The present system may be a physical computer system (one or more physical computers) or a system built on a calculation resource group (a plurality of calculation resources) such as a cloud foundation. The computer system or the calculation resource group includes one or more interface devices (e.g., including a communication device and an input/output device), one or more storage devices (e.g., including a memory (main storage) and an auxiliary storage device), and one or more processors. 
     In a case where the function is realized by executing the program by the processor, the determined process is appropriately performed using the storage device and/or the interface device, and thus the function may be at least a part of the processor. The process described with the function as the subject may be a process performed by a processor or a system including the processor. The program may be installed from a program source. The program source may be, for example, a program distribution computer or a computer-readable storage medium (e.g., a computer-readable non-transitory storage medium). The description of each function is an example, and a plurality of functions may be integrated into one function or one function may be divided into a plurality of functions. 
     [Outline] 
     Hereinafter, a system that supports development of a new compound by a user is disclosed. The system according to an embodiment of the present specification presents materials to be candidates for experiments and simulations to a user. The system quantifies the evaluation of the physical properties of the candidate material and the availability of the candidate material and calculates an evaluation value of the candidate material (hereinafter also referred to as overlooking evaluation value) based thereon. The system ranks the candidate materials according to their evaluation values and presents the high-ranking candidate materials to the user. 
     In this way, by quantifying the evaluation of each of the physical properties and the availability of the candidate material and selecting the candidate material to be presented to the user by the evaluation value obtained by combining the above, the possibility of presenting a material that is not available to the user can be reduced and the possibility of presenting a material having excellent physical properties even though the availability is low can be increased. Therefore, it is possible to efficiently search for a new material having desired physical properties by the user. 
     First Embodiment 
       FIG.  1    illustrates an example of a configuration of an experimental design support system that supports an experimental design of a compound (material) to be newly synthesized according to a first embodiment. Note that the user may design a simulation in addition to or instead of the compound experiment with the support of the present system. The system includes an experimental design support device  10  and a client computer  20  that can communicate with each other via a network. 
     The experimental design support device  10  presents candidates of a compound (material) for which the user newly conducts an experiment or simulation. Hereinafter, for ease of explanation, a candidate compound presented by the experimental design support device  10  is assumed as an experimental target candidate to be newly synthesized. In addition to displaying the candidate compound presented by the experimental design support device  10  to the user, the client computer  20  transmits feedback on the presented compound input from the user to the experimental design support device  10 . 
     In the configuration example of  FIG.  1   , the experimental design support device  10  includes a physical property estimation unit  11 , a candidate compound generation unit  12 , a candidate compound selection unit  13 , an overlooking risk evaluation unit  14 , and a displayed information transmission/reception unit  15 . These are programs. The experimental design support device  10  further stores an experimental database (DB)  16  and an availability database  17 . 
     The client computer  20  stores and executes a Web browser  21  which is a program. The Web browser  21  includes a candidate compound display unit  23 . This is an internal module of the Web browser  21 . 
       FIG.  2    illustrates a hardware configuration example of the experimental design support device  10  and the client computer  20 . In the configuration example of  FIG.  2   , the experimental design support device  10  includes a processor  205  having calculation performance and a DRAM  208  that provides a volatile temporary storage area for storing programs executed by the processor  205  and data. 
     The experimental design support device  10  further includes a communication device  206  that performs data communication with other devices including the client computer  20 , and an auxiliary storage device  207  that provides a permanent information storage area using a hard disk drive (HDD), a flash memory, or the like. 
     For example, the auxiliary storage device  207 , the experimental design support device  10  stores programs of the physical property estimation unit  11 , the candidate compound generation unit  12 , the candidate compound selection unit  13 , the overlooking risk evaluation unit  14 , the displayed information transmission/reception unit  15 , and the like. The auxiliary storage device  207  further stores various data such as the experimental database  16  and the availability database  17 . The programs executed by the processor  205  and the data to be processed are loaded from the auxiliary storage device  207  to the DRAM  208 . 
     Furthermore, the experimental design support device  10  includes an input device  210  that receives an operation from the user, and a monitor  209  (an example of an output device) that presents an output result in each process to the user. 
     The client computer  20  includes hardware components similar to those of the experimental design support device  10 , and the same components are denoted with the same reference numerals. Note that functions divided to a plurality of devices may be integrated in one device, or the plurality of functions may be distributed to more devices. In addition, distributed functions of a plurality of devices may be integrated in one device. As described above, the experimental design support device  10 , the client computer  20 , and the system including them include one or more storage devices and one or more processors. 
       FIG.  3    illustrates a configuration example of an experimental database  16 . The experimental database  16  stores information of the experiment results of the compound, and stores data of the material for which physical property values of interest have been measured. Each record stored in the experimental database  16  includes fields for an experiment ID  161 , a chemical formula 162, a physical property identifier  163 , and a physical property value  164 . 
     The experiment ID  161  indicates an ID uniquely indicating the experiment. A plurality of records include the same experiment ID  161 . As will be described later, the experimental design support device  10  presents candidates of a compound to be newly synthesized and experimented with respect to experimental data (record group) identified by the experiment ID. The chemical formula 162 indicates a chemical formula of the material to be experimented. The chemical formula includes a chemical structural formula and a composition formula, and an appropriate chemical formula is assigned according to the material. 
     The physical property identifier  163  indicates an identifier of the measured physical property value, for example, a type name of the physical property value. As the type of physical property value, both a type representing a physical property and a type representing a chemical property can be adopted. The physical property value  164  indicates a measured physical property value. Note that the experimental database  16  may include information on simulation result in addition to or in place of the experimental data. The physical property value  164  indicates a measurement value by simulation instead of a measurement value by experiment. 
       FIG.  4    illustrates a configuration example of an availability database  17 . The availability database  17  stores information on availability for the user of each of the plurality of materials. As will be described later, the availability database  17  stores information on feedback from the user with respect to the candidate compound presented to the user. The feedback includes information on the availability of the candidate compound. 
     In the example of  FIG.  4   , the records in the availability database  17  include fields for experiment ID  171 , chemical formula 172, and availability  173 . The experiment ID  171  indicates an ID uniquely indicating an experiment, and is common to the experiment ID  161  of the experimental database  16 . The chemical formula 172 indicates a chemical formula of the target material. The availability  173  indicates whether the target material is available to the user. 
     The compound unavailable to the user is a compound that the user does not use, and is, for example, a compound that cannot be synthesized or is not practical to the user from the standpoint of cost, yield, stability, or the like. The available materials are materials that a user may possibly use. Thus, the availability/unavailability of a material in the availability database  17  is designated by the user. 
     In the examples described below, the availability  173  of each record indicates one of “experimented”, “unavailable”, or “postpone”. “Experimented” indicates that the experiment of the material has been executed and is available to the user. “Unavailable” indicates that it is unavailable by the user. “Postpone” indicates that it is available to the user, but the experiment has been postponed. Note that these are examples, and the availability  173  can define an arbitrary category that indicates whether or not the material is available to the user. For example, “postpone” may be omitted and available material and unavailable material may be indicated regardless of the presence or absence of experiment. 
       FIGS.  5  and  6    schematically illustrate an outline of processing of the experimental design support system.  FIG.  5    illustrates a process of presenting an experimental candidate compound for the first time, and  FIG.  6    illustrates a second and subsequent experimental candidate compound presenting processes. The user conducts an experiment of a compound selected from the candidate compounds presented by the experimental design support system, and feeds back the experiment result to the experimental design support system. 
     The experimental design support system receives the feedback and presents the new candidate compound. The experimental design support system and the user repeat presentation of the candidate compound and the experiment. A new material search including these series of presentation and experiments is also referred to as a project. The same presentation process ID is assigned to the series of candidate presentation, and associated with the experiment ID. 
     Referring to  FIG.  5   , the user operates the client computer  20  with the input device  210  while referring to the screen of the monitor  209 . The user transmits a candidate presentation request  31  to the experimental design support device  10  through the candidate compound display unit  23  of the Web browser  21 . 
     In response to the received candidate presentation request  31 , the displayed information transmission/reception unit  15  of the experimental design support device  10  requests the candidate compound selection unit  13  to select a candidate compound to present to the user. The candidate compound selection unit  13  requests the candidate compound generation unit  12  to generate a candidate compound list. The candidate compound generation unit  12  generates a candidate compound list indicating the candidate compounds. 
     The candidate compound generation unit  12  generates a new compound from the compound of the experimental data corresponding to the candidate presentation request  31  in the experimental database  16 . In the embodiment of the present specification, the experimental database  16  stores in advance initial data corresponding to the candidate presentation request  31 . The candidate compound generation unit  12  may use data of a compound different from the experimental data (e.g., open data or initial data set in advance in the system). 
     The candidate compound selection unit  13  receives the candidate compound list from the candidate compound generation unit  12 . Furthermore, the candidate compound selection unit  13  requests the physical property estimation unit  11  to estimate the physical property value of each of the candidate compounds indicated by the candidate compound list. The physical property estimation unit  11  estimates a physical property value of each of the compounds listed in the candidate compound list through a method defined in advance. 
     As will be described later, for example, one physical property value may be estimated, or a probability distribution of the physical property values may be estimated. The estimated probability distribution also corresponds to the estimated physical property value. The number of physical property value types to be estimated may be one or more. Hereinafter, an example in which the number of physical property value types to be estimated is one will be specifically described. 
     The candidate compound selection unit  13  receives physical property values of each of the compounds listed in the candidate compound list from the physical property estimation unit  11 . The candidate compound selection unit  13  selects a candidate compound to present to the user from the candidate compound list based on the estimation result of the physical property value without considering the availability. 
     The candidate compound selection unit  13  passes information on each of the selected candidate compounds to the displayed information transmission/reception unit  15 . The displayed information transmission/reception unit  15  generates (data of) a candidate presentation screen  35  indicating information on each of the selected candidate compounds, and transmits the candidate presentation screen  33  to the client computer  20 . 
     The user executes the Web browser  21  on the client computer  20 , and the candidate compound display unit  23  displays the candidate presentation screen  33  on the monitor  209 . The user refers to the candidate presentation screen  33  to select a compound to be subjected to an experiment from among the candidate compounds. The user conducts experiments on the selected compounds and measures their physical property values. 
     Next, second and subsequent experimental candidate compound presenting processes will be described with reference to  FIG.  6   . After conducting an experiment of a compound selected from the previously presented candidate compounds, the user transmits the feedback thereof to the experimental design support device  10 . Specifically, the user operates the client computer  20  with the input device  210  while referring to the screen of the monitor  209 . The user transmits a candidate addition request  35  to the experimental design support device  10  through the candidate compound display unit  23  of the Web browser  21 . The candidate addition request  35  includes feedback information from the user with respect to a previous presentation candidate compound including experiment results. 
     The displayed information transmission/reception unit  15  of the experimental design support device  10  stores the feedback information included in the candidate addition request  35  in the experimental database  16  and the availability database  17 . The feedback information in the candidate addition request  35  includes information of the experiment result and information of availability designated by the user with respect to the previous presentation candidate compound. 
     Next, the displayed information transmission/reception unit  15  requests the candidate compound selection unit  13  to select a candidate compound to be additionally presented to the user. The candidate compound selection unit  13  requests the candidate compound generation unit  12  to generate a candidate compound list. The candidate compound generation unit  12  generates a candidate compound list indicating the candidate compounds. The candidate compound generation unit  12  generates, for example, a new compound from the compounds of the data of the experiment ID of the candidate addition request  35  in the experimental database  16 . 
     The candidate compound selection unit  13  receives the candidate compound list from the candidate compound generation unit  12 . Furthermore, the candidate compound selection unit  13  requests the physical property estimation unit  11  to estimate the physical property value of each of the candidate compounds indicated by the candidate compound list. The physical property estimation unit  11  estimates a physical property value of each of the compounds listed in the candidate compound list through a method defined in advance. The estimation of the physical property value is similar to the estimation of the physical property value in the first candidate compound presentation. The estimation method may be different between the first presentation and the second and subsequent presentations. 
     The candidate compound selection unit  13  receives physical property values of each of the compounds listed in the candidate compound list from the physical property estimation unit  11 . The candidate compound selection unit  13  further requests the overlooking risk evaluation unit  14  to evaluate the overlooking risk. The overlooking risk evaluation unit  14  calculates an overlooking risk evaluation value of each of the candidate compounds based on the estimated physical property value and the evaluation value of each availability of the candidate compound on which the candidate compound list is formed. The overlooking risk evaluation value indicates the priority to be presented to the user. 
     For example, the overlooking risk evaluation unit  14  evaluates the availability of the candidate compound based on the information in the availability database  17 . The availability for the user can be more appropriately calculated by calculating the availability evaluation value based on the information of the availability designated by the user. In another example, the overlooking risk evaluation unit  14  may evaluate the availability by an evaluation value (e.g., SA score) indicating the synthesis difficulty of the candidate compound. In this case, the availability database  17  can be omitted. 
     The candidate compound selection unit  13  acquires an overlooking risk evaluation value of each of the candidate compounds from the overlooking risk evaluation unit  14 . The candidate compound selection unit  13  ranks the candidate compounds based on the overlooking risk evaluation value, and selects a candidate compound to present to the user from the candidate compound list. The candidate compound selection unit  13  passes information on each of the selected candidate compounds to the displayed information transmission/reception unit  15 . 
     The displayed information transmission/reception unit  15  generates (data of) a candidate presentation screen  35  indicating information on each of the selected candidate compounds, and transmits the candidate presentation screen  33  to the client computer  20 . The user executes the Web browser  21  on the client computer  20 , and the candidate compound display unit  23  displays the candidate presentation screen  33  on the monitor  209 . The user refers to the candidate presentation screen  33  to select a compound to be subjected to an experiment from among the candidate compounds. The user conducts experiments on the selected compounds and measures their physical property values. 
     Hereinafter, details of the experimental candidate compound presenting process will be described.  FIG.  7    illustrates a flowchart of an example of a first experimental candidate compound presenting process. First, in step S 101 , the candidate compound display unit  23  executed by the client computer  20  transmits a candidate presentation request to the experimental design support device  10 . The user executes the browser  21  on the client computer  20 , and inputs information of the candidate presentation request in the screen displayed by the candidate compound display unit  23 . 
       FIG.  8    illustrates an example of a candidate presentation request input screen  91  displayed on the monitor  209  of the client computer  20  by the candidate compound display unit  23 . The candidate compound display unit  23  acquires the candidate presentation request input screen  91 , for example, from the experimental design support device  10 . The candidate presentation request input screen  91  includes an experiment name section  911 , a physical property value type section  912 , and a physical property value condition section  913 . 
     The user inputs an experiment name representing the current project in the experiment name section  911 . The experiment name is associated with the experiment ID. In the present example, the user selects an experiment name for which experimental data already exists from the pull-down menu. The user inputs a target physical property value type for which a request for a value exists in the physical property value type section  912 . In the present example, only one physical property value type is designated, but a plurality of physical property value types may be designated. 
     Furthermore, the user inputs a condition required for the physical property value of the above type. In the example of  FIG.  8   , the condition is maximization of a physical property value, minimization of a physical property value, or a target value of a physical property value. When the target value is set, a compound estimated to have a physical property value close to the target value is presented. 
     The candidate compound display unit  23  generates a candidate presentation request  31  from the information input to the candidate presentation request input screen  91 . FIG.  9  illustrates a configuration example of the candidate presentation request  31 . The candidate presentation request  31  includes fields for a candidate presentation process ID  311 , an experiment ID  312 , a physical property identifier  313 , and a search condition  314 . 
     The candidate presentation process ID  311  is blank (e.g., NULL value) in the initial state, and when the experimental design support device  10  receives the candidate presentation request  31 , the candidate presentation process ID  311  is assigned. The experiment ID  312  is an ID associated in advance with the experiment name  911  input by the user. The physical property identifier  313  indicates an identifier associated in advance with the input physical property value type  912 . The search condition  314  indicates the input condition  913 . Note that, in the present specification, the identifier and the ID are the same in that they are values for identifying a target. 
     Returning to  FIG.  7   , in step S 102 , the displayed information transmission/reception unit  15  receives the candidate presentation request  31 , and requests the candidate compound selection unit  13  for the corresponding experimental candidate compound. The displayed information transmission/reception unit  15  assigns a new candidate presentation process ID  311  to the candidate presentation request  31 . The displayed information transmission/reception unit  15  stores the candidate presentation request  31  in a database (not illustrated). The displayed information transmission/reception unit  15  requests the candidate compound selection unit  13  for an experimental candidate compound to present along with the candidate presentation request  31 . 
     Next, in step S 103 , the candidate compound generation unit  12  generates a candidate compound list. Specifically, the candidate compound selection unit  13  requests the candidate compound generation unit  12  to generate a candidate compound together with the candidate presentation request  31 . The candidate compound generation unit  12  generates a candidate compound list indicating the candidate compounds, and passes it to the candidate compound selection unit  13 . The candidate compound generation unit  12  can generate, for example, a new candidate compound through an arbitrary method from the compounds of the experimental data indicated by the experiment ID  312  in the experimental database  16 . 
     For example, the candidate compound generation unit  12  can generate a descriptor of a new compound from descriptors of existing compounds by a reinforcement learning model, a variational auto-encoder (VAE), a Generative Adversarial Network (GAN), or the like. 
     Next, in step S 104 , the physical property estimation unit  11  estimates the respective physical property values of the candidate compound list. Specifically, the candidate compound selection unit  13  requests the physical property estimation unit  11  to estimate the physical property value together with the candidate compound list. The physical property estimation unit  11  can estimate the physical property value of each compound in the candidate compound list from the descriptor of the compound using, for example, a machine learning model or a density functional method. For example, the physical property estimation unit  11  estimates a single physical property value or a probability distribution of the physical property values. One expected value (estimated value) can also be determined from the probability distribution. 
     Next, in step S 105 , the candidate compound selection unit  13  selects a compound whose estimated physical property value is close to the ideal value defined in the candidate presentation request. The candidate compound selection unit  13  selects a compound based on the condition designated by the candidate presentation request  31 . When maximization or minimization of the physical property values is designated, the ideal value is, for example, a maximum value or a minimum value in the estimated value. When the target value is designated, the ideal value is the target value. 
       FIG.  10    schematically illustrates processes of generation of a candidate compound, estimation of physical property values of the candidate compound, and selection of a compound to be presented from the candidate compound. As described above, the candidate compound generation unit  12  generates new candidate compounds (chemical formulas A to D) from the compounds in the experimental database  16 . The physical property estimation unit  11  estimates the value of the designated physical property value type of each of the candidate compounds. The candidate compound selection unit  13  selects high-ranking X compounds whose estimated physical property value is close to the ideal value. In the example of  FIG.  10   , two compounds (chemical formula B and chemical formula D) having the highest estimated physical property values are selected. 
     Returning to  FIG.  7   , in step S 106 , the displayed information transmission/reception unit  15  generates the candidate presentation screen  33  and transmits the screen to the client computer  20 . The candidate presentation screen  33  includes information on the candidate compound selected by the candidate compound selection unit  13 . For example, the candidate presentation screen  33  shows a chemical formula (chemical structural formula or composition formula) and an estimated physical property value of the candidate compound. The displayed information transmission/reception unit  15  stores information of the selected candidate compound in a database (not illustrated) in association with the candidate presentation request. In step S 107 , the candidate compound display unit  23  displays the candidate presentation screen  33  on the monitor  209 . 
     Next, the second and subsequent experimental candidate compound presenting processes (experimental candidate compound additional presenting process) will be described. In the second and subsequent times, the experimental design support device  10  performs an experimental candidate compound selection in consideration of the feedback information from the user. 
       FIG.  11    illustrates a flowchart of an example of second and subsequent experimental candidate compound presenting processes. First, in step S 201 , the candidate compound display unit  23  executed by the client computer  20  transmits a candidate addition request  35  including the feedback information from the user to the experimental design support device  10 . 
     The user executes the browser  21  on the client computer  20 , and inputs information of the candidate addition request in the screen displayed by the candidate compound display unit  23 .  FIG.  12    illustrates an example of a candidate addition request input screen  92  displayed on the monitor  209  of the client computer  20  by the candidate compound display unit  23 . The candidate addition request input screen  92  shows information on the previously presented candidate compound and feedback information with respect to the candidate compound input by the user in the screen  92 . The candidate addition request input screen  92  indicates a candidate presentation process ID common to candidate presentation in a series of one project. 
     For example, the user designates an experiment name and a candidate presentation process ID, and the candidate compound display unit  23  acquires a candidate addition request input screen  92  of the designated project from the experimental design support device  10 . Note that the experimental candidate compound presentation screen may have the section of the feedback information eliminated from the candidate addition request input screen  92  of  FIG.  12   . 
     The candidate addition request input screen  92  includes, for each candidate compound, a chemical formula section  921  and an estimated physical property value section  922 . The chemical formula section  921  indicates a chemical formula (chemical structural formula in  FIG.  12   ) of the candidate compound, and the estimated physical property value section  922  indicates an estimated physical property value by the experimental design support device  10 . The candidate addition request input screen  92  further includes a user feedback section  923 . 
     In the user feedback section  923 , the user inputs information on the availability of the candidate compound. In the example of  FIG.  12   , any one of “experimented”, “postpone”, or “unavailable” can be designated. In addition, in a case of experimented, the measurement value can be input. As described above, “experimented” and “postpone” indicate that the material is available (available material). “Experimented” indicates that measurement of the physical property value by experiment of the material has been conducted, and “postpone” indicates that no experiment has been conducted. “Unavailable” indicates that the material is unavailable to the user. When “experimented” is selected, the user also inputs the measurement value obtained by the experiment. 
     The candidate compound display unit  23  generates a candidate addition request  35  from the input user feedback information and information acquired from the experimental design support device  10  (displayed information transmission/reception unit  15 ) together with the candidate addition request input screen  92 .  FIG.  13    illustrates a configuration example of the candidate addition request  35 . The candidate addition request  35  includes fields for a candidate presentation process ID  351 , an experiment ID  352 , a physical property identifier  353 , a search condition  354 , and feedback data  355 . 
     The candidate presentation process ID  351  indicates an ID previously assigned to the experimental design support device  10 . The experiment ID  352 , the physical property identifier  353 , and the search condition  354  are the same as the information of the field having the same name in the candidate presentation request  31  of the same project. For example, the candidate compound display unit  23  acquires these values from the displayed information transmission/reception unit  15 . 
     The feedback data  355  indicates feedback information for each of the candidate compounds input by the user in the candidate addition request input screen  92 . In the example of  FIG.  13   , each record of the feedback data  355  includes fields for a chemical formula 541, a physical property value  542 , and availability  543 . The chemical formula 541 represents a chemical formula of the compound, and the physical property value  542  represents a physical property value measured by an experiment. The availability  543  indicates a category for the availability of the compound, specifically, any of “experimented”, “postpone”, or “unavailable”. Note that some data, for example, experimental data may not be included. 
     Returning to  FIG.  11   , in step S 202 , the displayed information transmission/reception unit  15  receives the candidate addition request  35  from the client computer  20 . The displayed information transmission/reception unit  15  stores the experimental data indicated by the candidate addition request  35  in the experimental database  16 , and stores information on the availability in the availability database  17 . As a result, the information stored in the two databases  16  and  17  can be increased. The displayed information transmission/reception unit  15  stores the candidate addition request  35  in a database (not illustrated) The displayed information transmission/reception unit  15  further requests the candidate compound selection unit  13  for an additional candidate compound to present along with the candidate addition request  35 . 
     Next, in step S 203 , the candidate compound generation unit  12  generates a candidate compound list. Specifically, the candidate compound selection unit  13  requests the candidate compound generation unit  12  to generate a candidate compound together with the candidate addition request  35  from which the feedback data  355  is eliminated. The candidate compound generation unit  12  generates a candidate compound list indicating the candidate compounds, and passes it to the candidate compound selection unit  13 . 
     The candidate compound generation unit  12  can generate, for example, a new candidate compound from the compounds of the data of the project of the experimental database  16 . In addition, a wider variety of candidate compounds may be generated by using data of compounds used in other applications. The candidate compound generation unit  12  may generate a new candidate compound from the available compounds of the project in the availability database  17 . As the new candidate compound, an unavailable compound may be generated. The candidate compound generation unit  12  refers to the availability database  17  and excludes the already presented compound from the candidate compound list. 
     Next, in step S 204 , the physical property estimation unit  11  estimates the respective physical property values of the candidate compound list. Step S 204  is similar to step  104  illustrated in  FIG.  7   . Next, in step S 205 , the candidate compound selection unit  13  executes a presentation candidate compound selecting process based on the user feedback. Details will be described later with reference to  FIG.  14   . 
     Next, in step S 206 , the displayed information transmission/reception unit  15  generates the candidate presentation screen  33  and transmits the screen to the client computer  20 . The information on the candidate presentation screen  33  is similar to the information on the candidate presentation screen  33  transmitted in step S 106  in  FIG.  7    except that the compound is different. The displayed information transmission/reception unit  15  stores information of the selected candidate compound in a database (not illustrated) in association with the candidate addition request. In step S 207 , the candidate compound display unit  23  displays the candidate presentation screen  33  on the monitor  209 . 
       FIG.  14    is a flowchart of an example of a candidate compound selecting process S 205  based on user feedback. In  FIG.  14   , first, in step S 301 , the candidate compound selection unit  13  associates each candidate compound with the corresponding estimated physical property value (expected value and variance G). The example described here estimates a probability distribution of the physical property values of the compound. As an example, the estimated physical property value is assumed to follow the Gaussian distribution. Such a probability distribution is obtained by, for example, a Gaussian process regression model. 
     Next, in response to the request from the candidate compound selection unit  13 , the overlooking risk evaluation unit  14  executes steps S 302  to S 305  for each candidate compound. First, in step S 302 , the overlooking risk evaluation unit  14  calculates the similarity between each of the compounds that are available (experimented or postpone) in the data of the current project in the availability database  17  and the candidate compound. Any method can be used to calculate the similarity of the compounds. The overlooking risk evaluation unit  14  selects the maximum value S 1  of the similarity. 
     Furthermore, in step S 303 , the overlooking risk evaluation unit  14  calculates similarity between each of the compounds unavailable in the data of the current project in the availability database  17  and the candidate compound. The overlooking risk evaluation unit  14  selects the maximum value S 2  of the similarity. 
     Furthermore, in step S 304 , the overlooking risk evaluation unit  14  calculates similarity between each of the compounds in the data of the current project in the experimental database  16  and the candidate compound. The overlooking risk evaluation unit  14  selects the maximum value S 3  of the similarity. 
     Next, in step S 305 , the overlooking risk evaluation unit  14  substitutes the estimated physical property values S 1 , S 2 , and S 3  into a predetermined mathematical formula to calculate an overlooking risk evaluation value. The overlooking risk evaluation unit  14  returns the calculated overlooking risk evaluation values of all the candidate compounds to the candidate compound selection unit  13 . In step S 306 , the candidate compound selection unit  13  selects a compound ranked high in the overlooking risk evaluation value as an experimental candidate to be presented. 
     An example of a method of calculating the overlooking risk evaluation value will be described. For example, the overlooking risk evaluation unit  14  can calculate the overlooking risk evaluation value f by the following mathematical formula (1). N represents a normal distribution. 
       [Mathematical formula 1] 
         f ( X,S   1   ,S   2   ,S   3 )=ln∫ X     0     ∞   N ( X−y ;σ) dy+lnS   1   −lnS   2   −lnS   3   (1)
 
     The above mathematical formula (1) can be used in an example in which the condition for improving the physical property value is maximized. In the above mathematical formula (1), X 0  is a target value determined from the maximum value in the experimental data, and is, for example, the maximum value itself or a value smaller or larger than the maximum value by a predetermined value. The integral value indicates a probability that the physical property value of the candidate compound becomes greater than or equal to X 0 , and indicates an evaluation value (physical property evaluation value) for the physical property value of the candidate compound. 
     The terms of the similarities S 1  and S 2  indicate evaluation values for the availability of the candidate compound. A high similarity with an available compound means that a probability that a candidate compound is available is high. In addition, the high similarity with the unavailable compound means that a probability that the candidate compound is unavailable is high. 
     The overlooking risk evaluation value f increases as the probability that the physical property value becomes greater than or equal to X 0  increases. In addition, it becomes larger the larger the similarity S 1  with the available compound, and smaller the larger the similarity S 2  with the unavailable compound. Furthermore, it becomes smaller the larger the similarity S 3  to the experimented compound. 
     Based on the overlooking risk evaluation value f, a candidate compound estimated to have high probability of being available and exhibit good physical property values (with high probability) can be included in the candidate compound list to be presented to the user. In addition, even when the probability of being unavailable is high, the candidate compound estimated to exhibit extremely good physical property values can be included in the candidate compounds to be presented. Furthermore, it is possible to improve the efficiency of the experiment by excluding a compound having a high similarity with the experimented compound from the presentation list. 
     An overlooking risk evaluation value under other conditions of physical property values can be calculated by modifying the above mathematical formula (1). When the condition for improving the physical property value is minimized, for example, X 0  in the above mathematical formula (1) is determined from the minimum value in the experimental data, and the range of integration is set to X 0  to −∞, so that the overlooking risk evaluation value can be calculated. When the condition for improving the physical property value designates a target value, for example, the overlooking risk evaluation value can be calculated by setting the integration range to a predetermined range including the target value. 
     In the calculation of the evaluation value of the physical property value, a numerical value of the estimated physical property value may be used instead of the probability distribution of the physical property value. The integral in the above mathematical formula (1) is replaced with a function of the numerical value estimated by the physical property estimation unit  11 . For example, the function of the condition of maximization becomes larger as the estimated value becomes larger, the function of the condition of minimization becomes larger as the estimated value becomes smaller, and the function of the condition for designating the target value becomes larger as it becomes closer to the target value. 
     The above mathematical formula (1) is an example, and the overlooking risk evaluation value may be calculated by other mathematical formulas. The above examples refer to the similarity with the experimented compound, but in other examples, reference to the similarity with the experimented compound may be omitted. The evaluation value of the availability may be calculated by a method different from the above method based on the similarities S 1  and S 2 . For example, an evaluation value (e.g., SA score) of the synthesis difficulty determined from the chemical formula of the compound may be used, and one of S 1  or S 2  may be omitted. In both methods, the availability evaluation value is calculated based on the chemical formula of the candidate compound. 
     The overlooking risk evaluation unit  14  may calculate a plurality of overlooking risk evaluation values by different mathematical formulas (different criteria). The candidate compound selection unit  13  selects a high-ranking candidate compound from the overlooking risk evaluation value for each of the different mathematical formulas. 
     For example, mathematical formulas having different priorities (contributions) of physical property values, availability, and dissimilarities to the experimented compound can be prepared. A high priority means that a change in the value causes a greater change in the overlooking risk evaluation value. 
     For example, by increasing the weighting coefficient of the integral term of the above mathematical formula (1), the contribution of the term to the overlooking risk evaluation value increases, and the possibility of obtaining a compound exceeding the past physical property value can be prioritized. The presentation of the unavailable compound can be more reliably avoided by configuring the mathematical formula so as to increase the contribution of the term of the similarity with the unavailable compound, that is, so as to greatly decrease the evaluation value with respect to the increase in the similarity with the unavailable compound. 
     The candidate compound selection unit  13  may exclude one of the similar candidate compounds from the candidate compounds to present. For example, the candidate compound selection unit  13  may calculate the similarity between the compounds selected in accordance with the overlooking risk evaluation value, and exclude a compound having a low overlooking risk evaluation value from the compounds having a similarity exceeding a threshold value. A dissimilar compound having a lower overlooking risk evaluation value may be selected instead of the excluded compound. As a result, the range of compound candidates to be presented to the user can be expanded, and more efficient or development can be made. 
     Second Embodiment 
     Hereinafter, a second embodiment will be described. Differences from the first embodiment will be mainly described. In the second embodiment, a history of presentation of candidate compounds is used in the calculation of the overlooking risk evaluation value. In the second embodiment, as the number of presentations of the candidate compound increases, the possibility that a candidate compound that has not been selected before will be presented increases. Thus, the number of experiments can be avoided from continuously increasing without specific candidate compounds being presented. This makes it possible to present, for example, a compound having low availability but exhibiting satisfactory physical property values, and to reduce the possibility that a desired compound cannot be obtained even if the experiment is repeated. 
       FIG.  15    illustrates a configuration example of a candidate addition request  35  according to a second embodiment. A field for the number of feedbacks  357  is added to the candidate addition request according to the first embodiment illustrated in  FIG.  13   . In this way, the present embodiment manages the number of feedbacks in the project, that is, the number of presentations of the candidate compound or the number of experiments. 
     For example, the displayed information transmission/reception unit  15  of the experimental design support device  10  manages a series of candidate addition requests, and includes information on the number of feedbacks in the data of the candidate addition request input screen  92  to be transmitted to the client computer  20 . The candidate compound display unit  23  of the client computer  20  stores the numerical value determined with reference to the number of times in the field for the number of feedbacks  357 . 
       FIG.  16    illustrates a configuration example of an availability database  17  according to the second embodiment. A field for the number of feedbacks  175  is added to the availability database according to the first embodiment illustrated in  FIG.  4   . The displayed information transmission/reception unit  15  stores the number of feedbacks indicated by the received candidate addition request  35  in the field for the number of feedbacks  175  together with other data. 
       FIG.  17    is a flowchart of an example of a candidate compound selecting process S 205  based on user feedback according to the second embodiment. Steps S 401  to S 403  are similar to steps S 301  to S 303  of the flowchart illustrated in  FIG.  14   . In step S 404 , the overlooking risk evaluation unit  14  calculates the maximum value S 4  of the number of feedbacks of the project in the availability database  17 . Step S 405  is similar to step S 304  of the flowchart illustrated in  FIG.  14   . 
     Next, in step S 406 , the overlooking risk evaluation unit  14  substitutes the estimated physical property values S 1 , S 2 , S 3  and S 4  into a predetermined mathematical formula to calculate an overlooking risk evaluation value. The overlooking risk evaluation unit  14  returns the calculated overlooking risk evaluation values of all the candidate compounds to the candidate compound selection unit  13 . In step S 407 , the candidate compound selection unit  13  selects a high-ranking compound in the overlooking risk evaluation value as an experimental candidate. 
     An example of a method of calculating the overlooking risk evaluation value will be described. For example, the overlooking risk evaluation unit  14  can calculate the overlooking risk evaluation value f by the following mathematical formula (2). 
       [Mathematical formula 2] 
         f ( X,S   1   ,S   2   ,S   3   ,S   4 ) =ln∫ X     0     ∞   N ( X−y ;σ) dy+lnS   1   −lnS   2   −lnS   3   +S   4  rand( )  (2)
 
     In the above mathematical formula (2), a random number element S 4 rand ( ) is added to the mathematical formula (1) in the first embodiment. rand( ) means a random number. The number of feedbacks S 4  increases with the number of experiments. Therefore, as the number of experiments (the number of presentations or the number of feedbacks) increases, the magnitude of the random number element S 4 rand( ) increases, and the contribution to the overlooking risk evaluation value f increases. 
     That is, regardless of the physical property value, the availability, and the similarity to the experimented compound, the overlooking risk evaluation value f of the randomly selected candidate compound increases. As a result, a compound under a condition that has not been selected so far is selected as a compound to be presented, and as the number of experiments increases, the possibility can be increased. 
     The overlooking risk evaluation unit  14  can calculate the overlooking risk evaluation value f by the following mathematical formula (3) in place of or in addition to the above mathematical formula (2). 
       [Mathematical formula 3] 
         f ( X,S   1   ,S   2   ,S   3   ,S   4 ) =ln∫ X     0     ∞   N ( X−y ;σ) dy +( lnS   1   −lnS   2   −lnS   3 )/ S   4   (3)
 
     In the above mathematical formula (3), a divisor S 4  for (lnS 1 −lnS 2 −lnS 3 ) is added to the mathematical formula (1) in the first embodiment. The number of feedbacks S 4  increases with the number of experiments. Therefore, as the number of experiments (the number of presentations) increases, the contribution of the evaluation value of an element other than the physical property value to the overlooking risk evaluation value f decreases. The priority of the physical property value in the overlooking risk evaluation value f is relatively high. That is, the possibility that a candidate compound exhibiting good physical property values is selected increases regardless of the availability and the similarity with the experimented compound. As a result, compounds that have not been selected due to factors other than physical property values can be included in the presentation list. 
     The candidate compound selection unit  13  may use, for example, one of mathematical formula (2) or mathematical formula (3) to select a candidate compound to present. A predetermined number of candidate compounds having a high overlooking risk evaluation value f are selected. In another example, the candidate compound selection unit  13  may select a predetermined number of candidate compounds high-ranking in the overlooking risk evaluation values f of each of the mathematical formulas (2) and (3). A more exhaustive candidate compounds can be selected by using a plurality of mathematical formulas. 
     Note that the present invention is not limited to the embodiments described above, and includes various modified examples. For example, the embodiments described above have been described in detail for the sake of easy understanding of the present invention, and are not necessarily limited to those having all the described configurations. In addition, a part of the configuration of a certain embodiment can be replaced with a configuration of another embodiment, and the configuration of a certain embodiment can be added with the configuration of another embodiment. Furthermore, for a part of the configuration of each embodiment, other configurations can be added, deleted, and replaced. 
     In addition, some or all of the above-described configurations, functions, processing units, and the like may be realized by hardware, for example, by designing with an integrated circuit. In addition, each of the above-described configurations, functions, and the like may be realized by software by a processor interpreting and executing a program for realizing each function. Information such as a program, a table, and a file for realizing each function can be stored in a recording device such as a memory, a hard disk, and a solid state drive (SSD), or a recording medium such as an IC card and an SD card. 
     In addition, control lines and information lines that are considered necessary for the description are shown, and not all control lines and information lines are necessarily shown in terms of product. In practice, it may be considered that almost all the configurations are connected to each other.