Antibody selection system and operation method therefor
Patent Information
- Application Number
- JP2024536758
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2022-07-29
- Filing Date
- 2022-07-29
- Publication Date
- 2025-04-16
- Estimated Expiration
- 2042-07-29
AI Technical Summary
Researchers face difficulties in selecting appropriate antibodies for antibody staining or immunoprecipitation due to limited information availability on antibody manufacturers' websites, making it challenging to identify suitable antibodies for specific genes and their related proteins, especially when investigating gene expression in disease-related tissues.
A system connected to an antibody information server that displays microscopic images and base sequences of biological tissues, allowing users to select genes, retrieve information on antibodies against encoded proteins, and order suitable antibodies through the internet, with features like GUIs for displaying antibody characteristics and staining results.
Facilitates easy selection and procurement of antibodies based on gene-specific requirements, enhancing the efficiency of gene expression investigation and providing a platform for sharing staining results, thus improving the antibody selection process for researchers.
Abstract
Description
System for selecting antibodies and method of operation thereof
[0001] The present invention relates to a system for selecting antibodies and a method of operating the same.
[0002] Once the gene that causes the disease is identified, researchers use antibody staining or immunoprecipitation to confirm the expression of the protein that the gene encodes and investigate the function of that gene. At this time, it is necessary to examine whether the expression of this causative gene and other related genes is increased or decreased when compared with the surrounding normal tissue.
[0003] 1) Which genes are related to the causative gene?
[0004] 2) If the relevant gene is identified, are there antibodies suitable for antibody staining or immunoprecipitation?
[0005] 3) Which manufacturer's antibody is suitable?
[0006] 4) Which antibody should I choose from antibodies from the same manufacturer?
[0007] 5) Information is needed on whether staining is successful when a certain antibody is used.
[0008] Such information often cannot be found on the antibody manufacturer's website alone.
[0009] An object of the present invention is to provide a system for easily selecting antibodies and a method for operating the system.
[0010] One embodiment of the present invention is a method for operating a system for selecting antibodies that is communicatively connected to an antibody information server, the system having a control device and a display device, the method including: a first step in which the control device causes the display device to display a microscopic image of a biological tissue or cell, a base sequence of a nucleic acid contained in the biological tissue or cell, data indicating characteristics of the nucleic acid or characteristics of the base sequence, and the names of one or more genes obtained based on the data; a second step in which the control device transmits to the antibody information server the ID of a gene selected from the one or more genes; a third step in which the control device receives from the antibody information server information on an antibody against a protein encoded by the selected gene; and a fourth step in which the control device causes the display device to display information on the antibody.
[0011] Other embodiments of the present invention will become apparent from the detailed description that follows.
[0012] 7A is a flowchart showing a method of operating a system for selecting an antibody in one embodiment of the present invention. FIG. 7B is a schematic diagram showing an overall view including a system for selecting an antibody, and other systems and an external server related to the system in one embodiment of the present invention. FIG. 7C is a diagram showing an example of the relationship between the system for selecting an antibody and an external server in one embodiment of the present invention. FIG. 7D is a diagram showing an example of the relationship between the system for selecting an antibody and an external server in one embodiment of the present invention. FIG. 7D is a diagram showing an example of the relationship between the system for selecting an antibody and an external server in one embodiment of the present invention. FIG. 7D is a diagram showing an example of the relationship between the system for selecting an antibody and an external server in one embodiment of the present invention. FIG. 7D is a diagram showing an example of the GUI displayed on a monitor in one embodiment of the present invention. FIG. 7D is a diagram showing an example of the GUI displayed on a monitor in one embodiment of the present invention.
[0013] The objectives, features, advantages, and ideas of the present invention will be apparent to those skilled in the art from the description in this specification, and those skilled in the art can easily reproduce the present invention from the description in this specification. The embodiments and specific examples of the invention described below show preferred embodiments of the present invention and are shown for illustrative or explanatory purposes, and are not intended to limit the present invention thereto. It will be apparent to those skilled in the art that various changes and modifications can be made based on the description in this specification within the spirit and scope of the present invention disclosed in this specification.
[0014] ==Main embodiments of the present invention== [1] A method for operating a system for selecting antibodies that is communicatively connected to an antibody information server, the system having a control device and a display device, the method including: a first step in which the control device causes the display device to display a microscopic image of a biological tissue or cell, a base sequence of a nucleic acid contained in the biological tissue or cell, data indicating characteristics of the nucleic acid or characteristics of the base sequence, and the names of one or more genes obtained based on the data; a second step in which the control device transmits to the antibody information server the ID of a gene selected from the one or more genes; a third step in which the control device receives from the antibody information server information on an antibody against a protein encoded by the selected gene; and a fourth step in which the control device causes the display device to display the information on the antibody.
[0015] [2] The method of claim [1], wherein the one or more genes include a first gene obtained based on the data and one or more second genes related to the first gene.
[0016] [3] The operating method described in item [1] or [2], further comprising a fifth step in which the control device orders the antibody or its production through the Internet or the antibody information server to which the system is communicatively connected.
[0017] [4] The operating method described in item [3] further includes a sixth step in which the control device causes the display device to display an image of biological tissue or cells stained using the antibody ordered in the fifth step and delivered to the orderer.
[0018] [5] The operating method described in item [3] or [4], further comprising a seventh step in which the control device transmits to the antibody information server an image of biological tissue or cells stained using the antibody ordered in the fifth step and delivered to the orderer.
[0019] [6] The antibody information server has a storage device that stores a list of information on one or more antibodies against proteins encoded by multiple genes, and the antibody information server receives the ID of the selected gene, identifies the selected gene in the list stored in the storage device, and transmits information on the antibody linked to the selected gene to the system. The operating method described in any one of [1] to [5].
[0020] [7] An operating method described in any one of items [1] to [6], wherein the first step includes a substep in which the control device receives the microscope image via the Internet.
[0021] [8] The operating method described in any one of items [1] to [6], wherein the system further has a microscope device, and the first step includes a substep of receiving the microscope image from the microscope device.
[0022] [9] The method of any one of items [1] to [8], wherein the first step includes a substep in which the control device receives the base sequence of the nucleic acid via the Internet.
[0023]
[10] The system further includes a base sequence analyzer, and the first step includes a substep in which the control device receives the base sequence of the nucleic acid from the base sequence analyzer. The operating method described in any one of items [1] to [9].
[0024]
[11] The method of operation described in items [1] to [6], [8], and [9], wherein the system further includes a base sequence analyzer, and the first step includes a substep in which the control device receives the base sequence of the nucleic acid from the base sequence analyzer, and the base sequence of the nucleic acid is the base sequence of a nucleic acid extracted from the biological tissue or cell.
[0025]
[12] The method of any one of items [1] to
[11] , wherein the first step includes a substep in which the control device receives data indicating characteristics of the nucleic acid or characteristics of the base sequence of the nucleic acid via the Internet.
[0026]
[13] The system further includes a genetic analysis device, and the first step includes a substep in which the genetic analysis device analyzes the base sequence of the nucleic acid to obtain data indicating characteristics of the nucleic acid or characteristics of the base sequence, and a substep in which the control device receives data indicating characteristics of the nucleic acid or characteristics of the base sequence from the genetic analysis device. The operating method described in any one of items [1] to
[12] .
[0027]
[14] The method according to any one of items [1] to
[13] , wherein the fourth step includes a substep in which the control device causes the display device to display the suitability of the antibody.
[0028]
[15] The operating method according to item
[14] , wherein the suitability is a compatibility.
[16] The operating method according to any one of items [1] to
[13] , wherein the fourth step includes a substep of causing the control device to display, on the display device, antibodies whose suitability satisfies a predetermined condition based on both the antibody information received in the third step and antibody information obtained via the Internet.
[0029]
[17] The method according to any one of items [1] to
[16] , wherein the characteristics of the nucleic acid or the characteristics of the base sequence are mutations in the base sequence, modification patterns of the nucleic acid, higher-order structures of the nucleic acid, or binding states of the nucleic acid with proteins.
[0030]
[18] The method of any one of items [1] to
[17] , wherein the information about the antibody against the selected gene includes an image of a biological tissue or cell stained with the antibody.
[0031]
[19] A program for selecting an antibody, the program causing the system to execute the method according to any one of items [1] to
[18] .
[0032]
[20] A storage medium storing the program according to item
[19] in a computer-readable manner.
[0033]
[21] A system for selecting antibodies that is communicatively connected to the Internet and communicatively connected to an antibody information server, the system having a control device and a display device, wherein the control device causes the display device to display a microscopic image of biological tissue or cells, a base sequence of nucleic acid contained in the biological tissue or cells, data indicating characteristics of the nucleic acid or characteristics of the base sequence, and the names of one or more genes obtained based on the data, the control device transmits the ID of a gene selected from the one or more genes to the antibody information server, the control device receives information on antibodies against proteins encoded by the selected genes from the antibody information server, and the control device causes the display device to display the information on the antibodies.
[0034]
[22] A system for ordering an antibody or its production, which is communicatively connected to the Internet and to an antibody information server, the system having a control device and a display device, wherein the control device causes the display device to display a microscopic image of a biological tissue or cell, a base sequence of a nucleic acid contained in the biological tissue or cell, data indicating characteristics of the nucleic acid or characteristics of the base sequence, and the names of one or more genes obtained based on the data, the control device transmits the ID of a gene selected from the one or more genes to the antibody information server, the control device receives information on an antibody against a protein encoded by the selected gene from the antibody information server, the control device causes the display device to display the information on the antibody, and the control device orders the antibody or its production via the Internet or the antibody information server.
[0035] System for Selecting Antibodies and Method for Operating the Same A method for operating a system for selecting antibodies (hereinafter sometimes referred to as an antibody selection system, or simply as a system) disclosed herein, which is communicatively connected to an antibody information server and has a control device and a display device, includes the following steps: a first step in which the control device causes the display device to display a microscopic image of a biological tissue or cell, a base sequence of the nucleic acid of the biological tissue or cell, data indicating characteristics of the nucleic acid or characteristics of the base sequence, and the names of one or more genes obtained based on the data; a second step in which the control device transmits the ID of a gene selected from the one or more genes to the antibody information server; a third step in which the control device receives information on antibodies against proteins encoded by the selected genes from the antibody information server; and a fourth step in which the control device causes the display device to display the antibody information. Typically, the control device is a CPU, and the display device is a monitor.
[0036] Each step will be described in detail below with reference to FIG.
[0037] <First step> First, the control device causes the display device to display a microscopic image of the biological tissue or cell, the base sequence of the nucleic acid contained in the biological tissue or cell, data indicating the characteristics of the nucleic acid or the base sequence, and the names of one or more genes obtained based on the data (102).
[0038] The microscopic image of the biological tissue or cell is not particularly limited, and may be a phase contrast image showing the morphology of the cell, a bright field image of cells stained with HE staining or the like, a fluorescent image of cells stained with an antibody, etc. The state of the biological tissue or cell is also not particularly limited, and may be a tissue culture or cell culture, or a tissue section such as a frozen section or paraffin section.
[0039] The microscope images may be received by the control device via the Internet, or may be received from a microscope device if the system has one. In the latter case, a user prepares biological tissues or cells, observes them under a microscope, and transmits the images captured using a CCD camera or the like to the control device.
[0040] The nucleic acid contained in the biological tissue or cells is the nucleic acid contained in at least some of the cells in the biological tissue or cells in the microscopic image, and may be derived from the same type of cell as the cell in the image, and may be nucleic acid extracted from the cell itself in the image, or nucleic acid extracted from a different cell of the same type as the cell in the image. The nucleic acid may be DNA or RNA.
[0041] The base sequence of this nucleic acid may be the entire base sequence of the nucleic acid or a desired portion of the base sequence. This base sequence may be obtained by the control device via the Internet, or the system may further include a base sequence analyzer that analyzes the base sequence of the target nucleic acid and transmits it to the control device. The nucleic acid analyzed by the base sequence analyzer may be extracted from at least some cells of the biological tissue or cells used to create the microscopic image, or may be extracted from cells of the same type as the cells in the image but different from them. The control device of this system may also use base sequences obtained and stored by another device or system from the Internet or a base sequence analyzer.
[0042] As used herein, homologous means of the same cell-type, and the nucleic acid may be obtained from the same tissue of the same individual as the biological tissue or cell used to generate the microscopic image, from the same tissue of a different individual but of the same biological species, from the same tissue of a different biological species, or from a homologous tissue of a different biological species.
[0043] Data indicating the characteristics of a nucleic acid or a base sequence refers to raw data, analytical data, or analytical data that indicate the physical or chemical characteristics of a nucleic acid or its base sequence, such as mutations in the base sequence (deletions, substitutions, insertions, or SNPs), nucleic acid modification patterns (e.g., the frequency and pattern of cytosine methylation), the higher-order structure of the nucleic acid (e.g., hairpin structure), and the binding state with a protein (e.g., the amount of histone binding).
[0044] The data indicating the characteristics of nucleic acids or base sequences may be data obtained via the Internet by searching based on the base sequences of nucleic acids, but the system may also have a genetic analysis device and obtain data indicating the characteristics of nucleic acids or base sequences by analyzing the structure of nucleic acids, the base sequences of nucleic acids, interactions between nucleic acids and proteins, etc. Furthermore, the control device of this system may use data that another device or system obtains from the Internet or a base sequence analysis device and stores.
[0045] "One or more genes" obtained based on data indicating nucleic acid characteristics or base sequence characteristics refers to genes directly or indirectly related to the nucleic acid characteristics or base sequence characteristics. For example, "directly related genes" refer to genes that partially or completely contain a sequence having that characteristic. "Indirectly related genes" refer to genes related to directly related genes, such as genes whose expression is controlled by directly related genes, genes genetically upstream or downstream of directly related genes, genes encoding proteins upstream or downstream of proteins encoded by directly related genes in a signal transduction system, and genes encoding proteins that bind to sequences having that characteristic. Here, "gene" refers to the coding region and its expression control region. The expression control region may be upstream or downstream of the coding region. "Gene name" refers to a notation that can identify and identify an individual gene, a part of it, or a group of several genes, and may be represented by an ID such as a code or number. It is also possible that a gene cannot be obtained and displayed based on data indicating nucleic acid characteristics or base sequence characteristics.
[0046] The base sequence analyzer and gene analyzer may be connected to the control device via the Internet or directly via a LAN, etc. The base sequence analyzer and gene analyzer may be installed in an analysis facility independent of this system.
[0047] <Second Step> Next, the user selects one or more genes for which the user wishes to obtain an antibody to the protein they encode from the one or more genes obtained based on the data showing the nucleic acid characteristics or base sequence characteristics in the first step. The control device transmits the IDs of the selected genes to the antibody information server, which then receives the IDs (104).
[0048] The antibody information server and the system may be connected via the Internet or directly via a LAN.
[0049] The antibody information server preferably has a storage device, which may store a list of one or more antibodies against proteins encoded by various genes and information about the antibodies, including the epitope recognized by the antibody, sample images of biological tissues or cells stained with the antibody, the distributor of the antibody, characteristics of the antibody (monoclonal or polyclonal, the animal species from which it was produced, the fluorescent dye bound to it, suitable applications, etc.), and literature (e.g., patent documents, academic papers, etc.) describing experiments using the antibody.
[0050] <Third Step> Next, the antibody information server identifies the gene corresponding to the gene ID received in the second step, selects information on the antibody linked to that gene from the list (106), and transmits this information as antibody information to the system (108). If there is no antibody linked to the gene corresponding to the gene ID received in the second step, information is transmitted to the system that no antibody against that gene exists in the list. The system control device thus receives information on antibodies against proteins encoded by the selected genes from the antibody information server.
[0051] <Fourth step> The control device displays on the display device the gene name linked to the ID sent to the antibody information server and the antibody information received from the antibody information server (110). If there is no antibody linked to the gene corresponding to the gene ID received in the second step, a message such as "No antibody" may be displayed. Alternatively, if there is no specific information about the antibody, a message such as "(Specific information) is not available" may be displayed.
[0052] <Step 5> The antibody information acquired by the control device from the antibody information server includes whether or not the antibody exists, and if the antibody exists, the antibody sales company, antibody characteristics, etc. If multiple antibodies exist, the user can select the antibody that is most suitable for their application based on the antibody's properties, etc. Then, using the control device, the user can order the selected antibody from a company that sells that antibody via the Internet or the antibody information server to which the system is communicatively connected (112). If the antibody does not exist, the user can order the production of an antibody against the desired gene from a company that produces antibodies.
[0053] The evaluation of antibodies for antibody selection or the selection of antibodies based on the evaluation may be automated.
[0054] For example, the control device may score antibody information acquired from the antibody information server, such as agreement with usage conditions, feedback on past purchase history, feedback on customer ratings, past purchase frequency, and literature information, as appropriateness, and display the products on the display device in order of highest score along with the score. Alternatively, a threshold for appropriateness may be set for the score, and one or more antibodies exceeding the threshold may be recommended. Here, appropriateness refers to the degree to which a person skilled in the art would determine that an antibody is appropriate from all aspects. For example, this appropriateness may be expressed as suitability, indicating the degree to which the user's requirements for the antibody are met. In this case, the user may input factors such as the antibody's intended use and application, and the control device may evaluate the suitability of each antibody based on those factors. Alternatively, the user may input the importance of each piece of information to the user's application, and the control device may evaluate the antibodies by taking the importance into account as a weight. In these cases, since past purchase frequency is a particularly effective evaluation for selecting a suitable antibody, evaluation based on other factors may be performed, and multiple antibodies with scores higher than the threshold may be selected, and then the suitability may be evaluated in descending order of past purchase frequency. This method allows the user to select the antibody that is considered to be most suitable for their purpose. Alternatively, the control device may automatically select the antibody with the highest suitability score and present it to the user. In this case, too, the antibody with the highest past purchase frequency may be selected from among antibodies with scores above a threshold, rather than just the score.
[0055] The literature information may be, for example, the impact factor of the journal in which the literature is published, the number of citations of the literature, etc., for a literature in which the antibody is used, preferably a literature in which a stained image of the antibody is published, if the literature is a paper. Here, the literature in which the antibody is used or the literature in which a stained image of the antibody is published may be analyzed using AI.
[0056] Alternatively, AI may be used to score the quality of the antibody for a photograph in which the antibody is used. For example, a stained image with a high background and a stained image with a low background may be trained as training data, and a score may be obtained that evaluates the level of background of the stained image obtained as described above.
[0057] The evaluation of antibodies for antibody selection may be based not only on antibody information acquired by the control device from an antibody information server, but also on antibody information acquired via the Internet. For example, in the case of literature information, stained images can be obtained from company websites or personal social networking sites.
[0058] <Sixth step> Meanwhile, the user can stain biological tissues or cells using the ordered antibodies, and the control device can then display an image of the stained biological tissues or cells on the display device.
[0059] By using this system in this way, it becomes possible to easily purchase antibodies against proteins encoded by genes related to the characteristics and base sequences of nucleic acids, and to easily examine the expression of those genes.
[0060] <Seventh step> The control device may transmit, as feedback to the antibody information server, images of biological tissues or cells stained with the antibody ordered in step 5 and delivered to the orderer in step 6. This allows other users connected to the antibody information server to share the results as reference data.
[0061] <Step 8> At any point during steps 2 to 7, the user can reselect one or more genes different from the gene selected in step 2 from among the one or more genes obtained based on the data showing the characteristics of the nucleic acid or the characteristics of the base sequence in step 1. In this case, for the newly reselected gene, steps 2 through 7 can be repeated, starting with the step in step 2 in which the control device transmits the ID of the newly selected gene to the antibody information server.
[0062] <Step 9> At any point during steps 5 to 7, it is possible to select a different antibody from the antibodies displayed in step 4 that is different from the antibody selected in step 5. In this case, the steps from ordering in step 5 to step 7 can be repeated for the newly selected antibody.
[0063] ==Program and Storage Medium== One embodiment disclosed in the present specification is a program for selecting an antibody, which causes a system to execute any of the methods described above. A storage medium storing this program in a computer-readable manner is also another embodiment of the present invention.
[0064] ==Relationship Between the System for Antibody Selection and External Server== The relationship between the system disclosed in this specification and the external server will be described in detail below with reference to Figures 2 to 6. Here, the external server is a server to which the antibody management system and / or antibody selection system is connected so as to be able to communicate via the Internet, and which has functions related to the system. External servers include publicly available servers that can be used free of charge or for a fee, and examples of such external servers include gene banks and protein banks such as EMBL, and article search engines such as PubMed.
[0065] (1) The overall picture of the antibody selection system, including other systems and external servers related to the system
[0066] First, an overview of the antibody selection system, including other systems and external servers related to the system, will be described with reference to FIG.
[0067] A user who wishes to order an antibody has the antibody selection system 300 disclosed herein. This antibody selection system 300 is connected to an antibody management system 302 via the Internet. This antibody management system 302 is connected via a LAN or the Internet to a system 304 that manages antibody information at antibody manufacturing companies and / or antibody sales companies, and manages information on antibodies manufactured and / or sold by the companies (e.g., antibody details and inventory numbers at each company). The antibody selection system 300 is also connected via the Internet to a reference genome data storage server 306, which allows users to obtain various genome information.
[0068] (2) Basic Configuration of Antibody Selection System FIGS. 3 to 6 show specific configuration examples of the antibody selection system.
[0069] First, the basic configuration common to these will be described.
[0070] The antibody selection system 300 disclosed herein includes an analysis / ordering computer 314 (hereinafter referred to as the computer), which serves as a control device, and a monitor 316, which serves as a display device. The system may also include a microscope 318. The system may also include a base sequence analyzer 320, a genetic analyzer 320, and an image information storage device 322, which may be integrated or independent devices. The image information storage device 322 stores images obtained by the microscope 318 or via the Internet. The image information storage device 322 may be a memory such as an external hard disk, an independent computer, or an internal memory of the analysis / ordering computer 314. In the figure, the base sequence analyzer 320 and the genetic analyzer 320 are shown as an integrated device, while the image information storage device 322 is shown as an independent device. These devices may be directly connected to the central system center containing the analysis / ordering computer 314 via a LAN, or may be independent analytical equipment connected to the central system center via the Internet. In this configuration, however, they are directly connected via a LAN.
[0071] An antibody management system 302 is provided independent of the antibody selection system 300. The antibody management system 302 may include an antibody production management system 324, an antibody count management system 326, and an antibody ordering system 328, and may be owned by an antibody sales company alone or jointly, or by an antibody management company. The antibody production management system 324 manages the production of antibodies sold by the company. For example, when the number of a specific antibody decreases in the antibody count management system 326, the antibody production management system 324 notifies the antibody production management system 324 of the name of the antibody and the remaining number of antibodies, and the antibody production management system 324 requests the company 304 or the antibody production system owned by the company 304 to start producing the antibody. When the company 304 produces an antibody and inputs this information into the antibody count management system 326, the antibody count management system 326 updates the number of antibodies produced. The antibody ordering system 328 receives an order for antibodies or antibody production from a user 312, and the company 304 sells the antibody to the user 312 in accordance with the order or produces the antibody at the request of the user 312. In the figure, communication with the user is performed exclusively by the antibody ordering system 328, but the antibody production management system 324 and antibody number management system 326 may also be configured to be able to communicate with the user 312. In addition to these systems, the antibody selection system 300 may be communicably connected via the Internet to public servers 306 such as gene banks, antibody banks, WWW servers holding reference genome data, and literature search engines.
[0072] A literature analysis unit may also be provided in the antibody selection system or antibody management system. The literature analysis unit may be provided anywhere in the antibody selection system or antibody management system, but is preferably provided in the antibody information server or analysis / ordering computer. The literature analysis unit is communicatively connected to literature databases, such as literature search engines outside the antibody selection system or servers of literature publishers, and searches literature published on the Internet to collect literature in which a specific antibody is used, preferably literature in which stained images of the antibody are published. The antibody is then scored based on the impact factors of the journals in which the papers are published and the number of citations of the papers, and the score is provided to the user along with antibody information.
[0073] Below are shown several examples of system configurations that differ depending on the location of the antibody information server 330.
[0074] (1) When the antibody information server 330 is located in the antibody management system 302: In Fig. 3, the antibody selection system 300 and the antibody information server 330 are connected via the Internet. The antibody information server 330 and the antibody ordering system 328 are connected via a LAN.
[0075] The antibody management system 302 can centralize information management by connecting to the systems of each antibody sales company 304 and obtaining information.
[0076] In this case, the antibody information server 330 can be connected to multiple antibody selection systems 300, thereby enabling connection to multiple users. This facilitates the accumulation of information through feedback, etc. in the antibody information server 330. The antibody management system may be placed on a so-called cloud.
[0077] (2) When the antibody information server 330 is connected to the antibody selection system 300 via a LAN
[0078] 4, the antibody selection system 300 and the antibody information server 330 are connected via a LAN, and the antibody information server 330 and the antibody ordering system 328 are connected via the Internet.
[0079] In this case, the antibody information server 330 connects to the systems of each antibody sales company 304 via the Internet and collects information.
[0080] The antibody information server 330 owned by each user 312 is connected to an antibody ordering system 328, and each user can place an order for the antibody or antibody production that they require.
[0081] (3) When the antibody information server 330 is located within the antibody ordering system 328 In Fig. 5, the antibody information server 330 is located within the antibody ordering system 328. This basically has the same effect as (1), but since the antibody information server 330 is located within the antibody ordering system 328, the antibody information in the antibody information server 330 can be updated more quickly.
[0082] (4) When there are multiple antibody information servers 330, each connected to the antibody selection system 300 via a LAN and connected to the antibody management system 302 via the Internet
[0083] In (2), the antibody management system 302 does not have an antibody information server 330, so even if the antibody management system 302 is connected to multiple users, it is not easy to receive feedback from the users. In the configuration shown in Figure 6, antibody information server A 330 is connected to the antibody selection system via a LAN, and antibody information server B 330 exists in the antibody management system 302. This allows users to freely manage antibody information using antibody information server A, and antibody information server B is connected to multiple users 312, allowing feedback from users 312 to be accumulated.
[0084] In this case, it is preferable that both antibody information server A330 and antibody information server B330 have a storage device that stores a list of information on one or more antibodies against proteins encoded by multiple genes. Antibody information server B330 creates the list by obtaining information from company 304. On the other hand, antibody information server A330 may create the list by obtaining information from the company, but it is preferable that it creates the list by obtaining information from antibody information server B330.
[0085] ==GUI== An example of a GUI for monitoring the antibody selection system is shown in Figure 7. Figure 7 illustrates the analysis of methylation in DNA sequences extracted from specific regions within a microscopic image of a biological tissue or cell. Note that this system is computer-controlled.
[0086] 7B displays a microscopic image of biological tissue or cells, in this example a brightfield image of an HE-stained mouse embryo tissue section acquired by a user using the microscope device 318.
[0087] The user collects cells from each region (ROI 1 to n) from the tissue section, isolates genomic DNA from the collected cells, and determines the base sequence using a sequencer (base sequence analyzer / genetic analyzer 320).Then, the base sequence data for the specified chromosomal region and the deduced amino acid sequence obtained from it are displayed on the monitor (Figure 7E).
[0088] At the same time, the cytosine methylation of DNA obtained from cells in different ROIs was analyzed in the area displayed on the monitor as a gene ruler (top of Figure 7F). The results were analyzed by computer, and a methylation score was calculated and displayed as a graph on the monitor (bottom of Figure 7F).
[0089] In the method for calculating a score related to methylation, for example, the methylation frequency, i.e., the proportion of methylated bases among a specific type of base detected at a specific position or region on the genome, or the methylation amount, i.e., the number of methylations detected at a specific position or region on the genome, may be converted into a score. Alternatively, the change in the methylation rate or methylation amount may be converted into a score.
[0090] In a specific genomic DNA region, a score for nucleic acid methylation is determined for each ROI, and the ROIs are sorted in descending order (Figure 7A). The methylation scores may also be visualized on the image. For example, the corresponding ROIs may be colored according to their methylation scores, and the results may be displayed in a heatmap format overlaid on a bright-field image of a HE-stained mouse embryo tissue section (Figure 7B). Here, for example, the user may select ROI1, which has the highest score.
[0091] At the top of Figure 7F, along the gene ruler, the names and IDs of genes present in the described DNA region, genes in or near the base sequence, genes genetically downstream of the gene, genes encoding proteins that bind to the base sequence, etc. may be written at the position of the related base sequence.
[0092] When the user selects a gene of interest from among these genes and clicks on the gene name, a list of commercially available antibodies linked to the gene name and sent from the antibody information server is displayed in the position shown in Figure 7D, as shown in Figure 8. If the user subsequently selects a new gene, a list of antibodies for the newly selected gene is similarly displayed.
[0093] 8, information on each antibody can be obtained, such as the antibody manufacturer, antibody clonality, immunized animal species, fluorescent modification, enzyme modification, etc. All or part of this list may be displayed in a pull-down format.
[0094] When the user clicks on the column of an antibody of interest in list D1 of FIG. 8, details of that antibody are displayed, as shown in list D11 of FIG. 9 or list D12 of FIG.
[0095] Furthermore, when the user clicks on an antibody manufacturer of interest (e.g., Company A) in list D2 of Fig. 8, a list of antibodies produced by the same antibody manufacturer (here, Company A) is displayed, as shown in list D21 of Fig. 9. When the user clicks on an antibody of interest (e.g., a mouse-derived monoclonal antibody) in list D21 of Fig. 9, a list in Fig. 9D11 displays details of the clicked antibody.
[0096] Next, when the user clicks on an immunized animal species of interest (e.g., rat) in list D3 of Fig. 8, a list of antibodies produced in the same immunized animal species (here, rat) is displayed, as shown in list D31 of Fig. 10. When the user clicks on an antibody of interest (e.g., an antibody from manufacturer C) in list D31 of Fig. 10, a list in Fig. 10D12 displays details of the clicked antibody.
[0097] In this embodiment, antibody manufacturers or immunized animal species are used as examples, but antibodies may also be classified by experimental use (e.g., tissue staining, immunoprecipitation, Western blotting, etc.), antibody species (e.g., IgM, IgG, etc.), modifiers (e.g., fluorescent dyes, enzymes, etc.), etc., and sublists of antibodies such as List D21 and List D31 may be created using these as indices. Alternatively, sublists with two indices may be created by extracting antibodies with a second indices from a sublist created with a first indices and creating a further sublist.
[0098] In this way, when an antibody of interest is selected and clicked from the antibody list, detailed information about that antibody is sent from the antibody information server, as shown in FIG. 7D. At the same time, if an image stained with that antibody is included in the antibody information, it is displayed in FIG. 7C. If an image stained with that antibody is not included in the information, a message such as "There are no images of stained samples for the selected antibody" may be displayed, as shown in FIG. 11.
[0099] Furthermore, if the user reselects an antibody from the antibody list, detailed information about the newly selected antibody is similarly displayed.
[0100] Next, when the user finds an antibody from the list of commercially available antibodies that they would like to purchase or for which they would like to obtain a sample, they can order the antibody or sample by clicking the icon labeled "Order / Request Sample" in Figure 7D, which allows them to select whether to order the antibody or request an antibody sample. At the same time, Figure 7G shows a list of reagents (such as secondary antibodies and enzyme substrates) that are useful when using the antibody, and the user can use this information for actual testing.
[0101] An object of the present invention is to provide a system for easily selecting antibodies and a method for operating the system.
[0102] 300: Antibody selection system 302: Antibody management system 304: Company 306: Public server 312: User 314: Analysis / ordering computer 316: Monitor 318: Microscope device 320: Genetic analysis device 322: Image information storage device 324: Antibody production management system 326: Antibody number management system 328: Antibody ordering system 330: Antibody information server
Claims
1. 1. A method of operating a system for selecting an antibody, communicatively connected to an antibody information server, comprising: The system includes a controller and a display device; The control device causes the display device to A microscopic image of a biological tissue or cell; A base sequence of a nucleic acid contained in the biological tissue or cell; Data indicating characteristics of the nucleic acid or characteristics of the base sequence; the name of one or more genes obtained based on said data; A first step of displaying a second step in which the control device transmits an ID of a gene selected from the one or more genes to the antibody information server; a third step in which the control device receives information on an antibody against a protein encoded by the selected gene from the antibody information server; a fourth step in which the control device causes the display device to display information about the antibody; The method of operation includes:
2. The method of claim 1 , wherein the one or more genes include a first gene obtained based on the data and one or more second genes related to the first gene.
3. The method of claim 1 , further comprising a fifth step of the control device ordering the antibody or its production through the Internet or the antibody information server to which the system is communicatively connected.
4. The control device causes the display device to 4. The method of claim 3, further comprising a sixth step of displaying an image of biological tissue or cells stained using the antibody ordered in the fifth step and delivered to the orderer.
5. The operating method according to claim 3, further comprising a seventh step in which the control device transmits to the antibody information server an image of a biological tissue or cell stained using the antibody ordered in the fifth step and delivered to the orderer.
6. the antibody information server has a storage device for storing a list of information on one or more antibodies against proteins encoded by a plurality of genes; The operating method according to any one of claims 1 to 5, wherein the antibody information server receives an ID of the selected gene, identifies the selected gene in the list stored in the storage device, and transmits information on the antibody linked to the selected gene to the system.
7. The first step is A method according to any one of claims 3 to 5, comprising the sub-step of the control device receiving the microscopic images via the internet.
8. The system further comprises a microscope device; The first step is receiving the microscopy image from the microscopy device The method of any one of claims 1 to 5, comprising:
9. The first step is said control device receiving said nucleic acid sequence via said internet; The method of any one of claims 3 to 5, comprising:
10. The system further comprises a base sequence analyzer, The first step is the control device receiving the base sequence of the nucleic acid from the base sequence analyzer. The method of any one of claims 1 to 5, comprising:
11. The system further comprises a base sequence analyzer, The first step is the control device receiving the base sequence of the nucleic acid from the base sequence analyzer. Including, The method according to any one of claims 1 to 5, wherein the nucleic acid base sequence is a nucleic acid base sequence extracted from the biological tissue or cell.
12. The first step is the control device receiving data indicative of a characteristic of the nucleic acid or a characteristic of a base sequence of the nucleic acid via the internet. The method of any one of claims 3 to 5, comprising:
13. The system further comprises a genetic analyzer; The first step is a sub-step of the gene analysis device analyzing the base sequence of the nucleic acid to obtain data showing characteristics of the nucleic acid or characteristics of the base sequence; a sub-step of the control device receiving data indicating characteristics of the nucleic acid or characteristics of the base sequence from the genetic analysis device; The method of any one of claims 1 to 5, comprising:
14. The fourth step is a sub-step of causing the control device to display the suitability of the antibody on the display device; The method of any one of claims 1 to 5, comprising:
15. The method of claim 14 , wherein the measure of suitability is a measure of compatibility.
16. The fourth step is a sub-step of causing the control device to display, on the display device, antibodies whose suitability satisfies a predetermined condition based on both the antibody information received in the third step and the antibody information acquired via the Internet. The method of claim 14, comprising:
17. The method according to any one of claims 1 to 5, wherein the characteristic of the nucleic acid or the characteristic of the base sequence is a mutation in the base sequence, a modification pattern of the nucleic acid, a higher-order structure of the nucleic acid, or a binding state of the nucleic acid with a protein.
18. A method according to any one of claims 1 to 5, wherein said information of an antibody against a protein encoded by said selected gene comprises an image of biological tissue or cells stained with said antibody.
19. A program for selecting an antibody, the program causing the system to execute the method according to any one of claims 1 to 5.
20. A storage medium storing the program according to claim 19 in a computer readable manner.
21. A system for selecting an antibody, the system being communicatively connected to the Internet and to an antibody information server, the system comprising: The system includes a controller and a display device; The control device may include: A microscopic image of a biological tissue or cell; A base sequence of a nucleic acid contained in the biological tissue or cell; Data indicating characteristics of the nucleic acid or characteristics of the base sequence; the name of one or more genes obtained based on said data; Display The control device includes: Transmitting an ID of a gene selected from the one or more genes to the antibody information server; The control device receives information on an antibody against a protein encoded by the selected gene from the antibody information server, The control device may include: Displaying information about the antibody; system.
22. A system for ordering an antibody or its production, which is communicatively connected to the Internet and to an antibody information server, comprising: The system includes a controller and a display device; The control device may include: A microscopic image of a biological tissue or cell; A base sequence of a nucleic acid contained in the biological tissue or cell; Data indicating characteristics of the nucleic acid or characteristics of the base sequence; the name of one or more genes obtained based on said data; Display The control device includes: Transmitting an ID of a gene selected from the one or more genes to the antibody information server; The control device receives information on an antibody against a protein encoded by the selected gene from the antibody information server, The control device may include: Displaying information about the antibody; The control device includes: ordering the antibody or its production through the internet or the antibody information server; system.