Bespoke site-business functionality

Brief outline

If you intend to use the client portal to directly access your site’s compound data then all the code to do so will need to be written.

To assist in this process there is the generic site-business component available in the portal repository which represents a fictional site compound database - this component mirrors the configuration required for your site’s data to be passed to the generic business-manager processing via the business-manager-api.

Task responsibility

The primary objective of this activity involves a good deal of cooperation between the scientists and the relevant IT personnel in the organisation to determine how to extract the requisite assay data from the site databases.

The IT people involved will need to have some experience of Java software development (including Spring), as well as XML formats.

Technical Process

  1. For the of the installation of the generic portal components each component’s configuration requires the creation and assignment of site-specific files and values. Much of this process is based on deriving actual files from generic sample.X template files and then modifying their content to a site’s requirements by following each component’s specific installation instructions (e.g. as in the installation instructions).
  2. For a bespoke site-business component there will be additional steps required (illustrated below) which will ultimately make use of a Maven WarPath plugin to overlay site-specific functionality over compiled and Maven-installed business-manager code.

The structure below and explanations thereafter (taken from the sample site-business component used for demonstration purposes), can be used to explain specifications and operations of generally required bespoke site-business functionality.

site-business/src/main/java/uk/ac/ox/cs/epsrc/site_business/business/selection/maxresponse/CSDemoMaxRespStrategy.java                 --+
               |    |                                |          |                    +----/CSMaxRespDataSelector.java                   |
               |    |                                |          +---/SiteDataLoader.java                                                |
               |    |                                |-----/dao/SiteDAOImpl.java                                                        |
               |    |                                |-----/request/validator/SiteSimulationsRequestValidator.java                      |
               |    |                                |-----/service/ExperimentalDataServiceImpl.java                                    |
               |    |                                |-----/SiteIdenifiers.java                                                         |-- 1
               |    |                                +-----/value/object/datarecord/doseresponse/CSDoseResponseDataRecordVO.java        |
               |    |                                                         |----/individual/CSIndividualDataRecordVO.java            |
               |    |                                                         |          |----/CSManualPatchCaV12DataRecordVO.java      |
               |    |                                                         |          |----/CSManualPatchHERGDataRecordVO.java       |
               |    |                                                         |          +----/CSManualPatchNaV15DataRecordVO.java      |
               |    |                                                         +----/summary/CSSummaryDataRecordVO.java                --+
               |    |-/resources/log4j.xml
               |    |      +----/META-INF/properties/.gitignore
               |    |                |         +----/README
               |    |                |---/spring/ctx/appCtx.business.site.xml
               |    |                |            |-/config/appCtx.config.actionPotential.site.xml                                    --+
               |    |                |            |    |---/appCtx.config.assays.site.xml                                               |
               |    |                |            |    |---/appCtx.config.cellModel.site.xml                                            |
               |    |                |            |    |---/appCtx.config.changeCheckers.site.xml                                       |-- 2
               |    |                |            |    |---/appCtx.config.doseResponseFitting.site.xml                                  |
               |    |                |            |    |---/appCtx.config.ionChannels.site.xml                                          |
               |    |                |            |    |---/appCtx.config.pc50Evaluators.site.xml                                       |
               |    |                |            |    +---/appCtx.config.site.xml                                                    --+
               |    |                |            |-/data/site/appCtx.database.site.xml                                               ----- 3
               |    |                |            +-/integration/simulation/processing/experimental/appCtx.proc.site.experimental.xml --+
               |    |                |                                           |----/qsar/appCtx.proc.site.qsar.xml                   |-- 4
               |    |                |                                           +----/screening/appCtx.proc.site.screening.xml       --+
               |    |                +---/sql/site/site.embedded.sql                                                                  --+__ 5
               |    |                           +-/site.mysql.sql                                                                     --+
               |    +-/webapp/WEB-INF/spring/spring-site-config.xml
               |-/properties/database/site/.gitignore                                                                                 --+
               |       |                |-/README                                                                                       |-- 6
               |       |                +-/sample.site.database.properties                                                            --+
               |       |----/.gitignore                                                                                               --+__ 7
               |       +----/sample.env.properties                                                                                    --+
               +-/test/ ....                                                                                                          ----- 8

1 - Writing the Java classes

Java classes used to :

  1. Define site-specific data record structures derived from business-manager-api (e.g. extending AbstractIndividualDataRecordVO as in the case of CSManualPatchHERGDataRecordVO).
  2. Query the site database to load site data into those data records.
    For this the relevant SQL will most likely need defining to extract all the relevant information from the site databases.
  3. Return the site data to the generic business-manager processing.
  4. pIC50 evaluation.

2 - Define CellMLs, Assays, Ion Channels, etc.

Note

A site’s configuration files are ultimately derived from the XML files in the business-manager sample configs directory. Examples of how these templates are copied and modified to fit to a site’s unique specifications is demonstrated in the site-business component configs.

XML configuration files to define a site’s unique setup.

  1. appCtx.config.actionPotential.site.xml : ApPredict invocation settings.

    1. Default frequencies and compound concentrations in situations where there is no experimental data available (ApPredict’s --pacing-freq and --plasma-concs arg. values).
    2. Default credible interval percentiles (ApPredict’s --credible-intervals arg. value). [2]
      The extension of functionality of this argument appeared around end-May 2018 to improve on the previous use of an unmodifiable singular default credible interval percentile of 95%.
    3. Default maximum pacing time (ApPredict’s --pacing-max-time arg. value).
    4. Default plasma concentration count (ApPredict’s --plasma-conc-count arg. value).
    5. Default plasma concentration log scale (ApPredict’s --plasma-conc-logscale arg. value).

  2. appCtx.config.assays.site.xml : Assay details.

    1. Assay names.
    2. Assay levels. [1]
      Assays in AP-Portal are considered to be hierarchical and a level value is assigned to each assay. Historically the hierarchy has reflected assay accuract, with the least accurate assay assigned a level value of 0 (zero), and increasingly more accurate assays assigned incremental level values.
    3. Assay groups. [1]
      When different assays have similar characteristics they can be grouped, and as with assay levels, the grouping is hierarchical. Historically the assay groups levels assigned have mirrored the assay levels assigned, with the least accurate groups assigned a group level of 0 (zero) and increasingly more accurate assay groups assigned incremental group level values.
    4. Assay variability. [2]

  3. appCtx.config.cellModel.site.xml : CellML models.

    The collection of CellML models contained in this configuration file must correspond to the CellML models which ApPredict is expecting.
    If you are uncertain which CellML models ApPredict has been built to work with, then invoke ApPredict at the command line with no arguments supplied, which should generate output containing something like the following :

    ***********************************************************************************************
* ApPredict::Please provide some of these inputs:
*
* EITHER --model
*   options: 1 = Shannon, 2 = TenTusscher (06), 3 = Mahajan,
*            4 = Hund-Rudy, 5 = Grandi, 6 = O'Hara-Rudy 2011 (endo),
*            7 = Paci (ventricular), 8 = O'Hara-Rudy CiPA v1 2017 (endo)
*            9 = Faber-Rudy.
* OR --cellml <file>

    It’s unlikely that the CellML models data would need to change except in the specification of the defaultModel - i.e. the model which should appear selected by default in the UI.

  4. appCtx.config.changeCheckers.site.xml - Change checkers.

    Change checkers should generally not require modification.

  5. appCtx.config.doseResponseFitting.site.xml - Dose-Response data fitting preferences.

    Only relevant if dose-response data fitting.

  6. appCtx.config.ionChannels.site.xml - Active ion channels.

    Collection of the actively tested ion channels.

  7. appCtx.config.pc50Evaluators.site.xml - pIC50 evaluators.

    pIC50 evaluation involves activating/deactivating and arranging evaluators according to site requirements.
    It is likely that the scientists will need to be consulted on which evaluators are to be used and their hierarchical order (0 (zero) being the first evaluator to seek a pIC50 value from). From experience it is likely that additional site-specific evaluators which also need to be implemented.

  8. appCtx.config.site.xml - Various client options settings.

    1. defaultForceReRun - use with care!
    2. Assay value inheritance defaults.
    3. Information display levels.
    4. defaultQuietPeriod - Time (in minutes) following a simulation’s run or re-run check in which another re-run check will not be undertaken.
      This is to avoid multiple concurrent requests to view a compound resulting in simulation re-runs.

3 - Connecting to the site’s database

Connectivity to the site’s database.

4 - Define Screening, QSAR, Experimental processing

Different sources of data to process, e.g. screening, QSAR, experimental data.

5, 6 - Ignore

(Sample site database structure)

7 - Define programming environment properties

Sample environment properties.

8 - Writing the Java unit testing classes.

Java test classes.

Footnotes

[1](1, 2) assay levels and assay group levels are used in assay value inheritance.
[2](1, 2) See also Variability Configuration.