CPIC Kit Get Started Guide

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KGrid CPIC Kit packages Activator, Library and CPIC Demo Site. The kit is designed as a personal CPIC Knowledge Grid used to explore the capabilities of KGrid and CPIC Knowledge Objects.

Installation

To setup the CPIC Kit you need:

To verify the versions for installed software, type in the following in you terminal widow :

java -version                     # JAVA version
npm version                       # node/npm version
  1. Download the latest CPIC Kit cpic-kit.zip from GitHub, GitHub CPIC Kit Release.
  2. Unzip cpic-kit.zip to a directory of your choice.
  3. Via a terminal interface navigate to the cpic_kit directory and install the kit

For example to create a cpic-kit directory in my projects directory and install the kit:

unzip cpic-kit.zip -d /Users/me/projects
cd /Users/me/projects/cpic-kit
npm install

The install process is downloading the KGrid applications (library and activator) and loading the CPIC Knowledge Objects into the system.

When complete you should see a similar message

Clean up complete
Load KGrid Assets
Downloading kgrid-activator-1.0.1.jar
Downloading kgrid-library-1.0.9.jar
Downloading cpic-all.zip
cpic-all.zip downloaded to dist
kgrid-activator-1.0.1.jar downloaded to activator
kgrid-library-1.0.9.jar downloaded to library
*********************************
*    KGRID INSTALL COMPLETE     *
*                               *
* Type 'npm start' to run KGrid *
*                               *
*********************************

Usage

Starting KGrid CPIC Kit

Starting the KGrid CPIC Kit will start up an instance of the KGrid Activator, KGrid Library and CPIC Kit Web. The CPIC Kit Web server will serve the CPIC web demo application.

From the command line of the kit directory start the kit.

npm start

When complete you should see a similar message

Starting KGrid CPIC Kit
Starting CPIC Kit demo web site on http://localhost:8083
Starting library on http://localhost:8081
Starting activator on http://localhost:8082
Waiting.....
KGrid CPIC Kit is running

Once started you can navigate to the Web and Command Line Demo clients as well as access the KGrid Library and KGrid Activator.

  1. Web Demo Client
  2. Command Line Demo Client
  3. KGrid Library
  4. KGrid Activator

Web Demo

This app simulates a panel of a patient's genotype and diplotype and generates drug dosing recommendations. Geno-to-pheno Knowledge objects are used to determine each gene's phenotype, if applicable. Relevant drugs recommendations are then determined based on the available genetic information, using the drug dosing recommendation KO.

To access the demo,

For Mac, type open http://localhost:8083;

For Windows, type start http://localhost:8083

To run the app,

  • Click on the button to select a patient, the preset data will be auto filled in the input panel and results will displayed;
  • You can manually change diplotype information in the input panel, the phenotype result and recommendation will be updated accordingly;

Note:

  • Click on the setting (gear icon) in the right upper corner, an overlay will allow you to choose a different activator;
  • Click on the app log, the log area will expand to show more details on the interactions with the connected KGrid activator.

Batch Command Line Demo

The Batch Command Line demos showcase an integration scenario. The process consumes a collection of patient's gene lab panel and returns the corresponding drug selection or dosing guideline recommendation based on a patient's gene alleles

Below we show examples of the inputs and outputs of this process

Gene Lab Panel

Input to the recommendation process is a patient gene lab panel

{
    "patient": {
        "name": "Hank Hill",
        "id": "1"
    },
    "diplotype": {
      "CYP2C19": "*1/*11",
      "CYP2C9": "",
      "CYP2D6": "*3/*3",
      "CYP3A5": "",
      "HLA-B": "*1/*1",
      "SLCO1B1": "",
      "TPMT": "",
      "UGT1A1": "*1/*1"
    },
    "prescriptions": "atazanavir codeine abacavir"
  }
}

CPIC Recommendation

The output of the recommendation process is a patient's CPIC Recommendation

 {
  "patient": {
    "name": "Hank Hill",
    "id": "1"
  },
  "time": "10/12/2018, 2:43:15 PM",
  "recommendations": [
    {
        "type": "CPIC Recommendation",
        "drug": "Atazanavir",
        "genes": {
            "UGT1A1": {
                "diplotype": "*1/*1",
                "phenotype": "normal metabolizer"
            }
        },
        "recommendation": {
            "implication": "Reference UGT1A1 activity; very low likelihood of bilirubin-related discontinuation of atazanavir.",
            "content": "There is no need to avoid prescribing of atazanavir based on UGT1A1 genetic test result. Inform the patient that some patients stop atazanavir because of jaundice (yellow eyes and skin), but that this patient?s genotype makes this unlikely (less than about a 1 in 20 chance of stopping atazanavir because of jaundice).",
            "classification": "Strong"
        }
    },
    {
        "type": "CPIC Recommendation",
        "drug": "Codeine",
        "genes": {
            "CYP2D6": {
                "diplotype": "*3/*3",
                "phenotype": "poor metabolizer"
            }
        },
        "recommendation": {
            "implication": "Greatly reduced morphine formation following codeine administration, leading to insufficient pain relief. ",
            "content": "Avoid codeine use due to lack of efficacy. Alternatives that are not affected by this CYP2D6 phenotype include morphine and nonopioid analgesics. Tramadol and, to a lesser extent, hydrocodone and oxycodone are not good alternatives because their metabolism is affected by CYP2D6 activity; these agents should be avoided",
            "classification": "Strong"
        }
    },
    {
        "type": "CPIC Recommendation",
        "drug": "abacavir",
        "genes": {
            "HLA-B": {
                "diplotype": "*1/*1",
                "phenotype": ""
            }
        },
        "recommendation": {
            "implication": "Low or reduced risk of abacavir hypersensitivity",
            "content": "abacavir: Use abacavir per standard dosing guidelines",
            "classification": "Strong"
        }
    }
  ]
}

We have created a sample json panel file (cli-client/panel.json) with several patients to demonstrate the batch capability. The following example passing in the example panel to a node script which takes the patient's gene panel information and using the cpic services constructs a set of recommendation for that patient. The recommendation written out the recommendation.json file

Mac/Unix

cat cli-client/panel.json | node cli-client/cpic-recommendation.js > recommendations.json

Windows

type cli-client\panel.json | node cli-client\cpic-recommendation.js > recommendations.json

Local KGrid Library

The local KGrid Library manages the CPIC collection of Knowledge Objects.

For Mac, type open http://localhost:8081;

For Windows, type start http://localhost:8081

Local KGrid Activator

The local KGrid Activator activates the CPIC collection of Knowledge Objects.

To check the status of the activator,

For Mac, open http://localhost:8082/health

For Windows, start http://localhost:8082/health

Stopping KGrid CPIC Kit

Stopping the running KGrid activator, library and demo web site can be accomplished with the npm stop command

npm stop

A similar message will appear

Stopping Activator, Library and CPIC Demo web site
kill -15 229
kill -15 228
kill -15 89142

Troubleshooting & Debugging

Application Logs

On windows the activator, library and web demo components will start their own terminal window. The application logs will stream to those terminal windows

On macs the application logs will be stored in the cpic-kit/activator/activator.log and cpic-kit/library/libray.log files.

CPIC Kit Updates

Each time the CPIC Kit is started it will first check to see if there have been any updates to the Kit or it's dependencies. A KGrid Assets Status section will appear in the terminal window.


       KGrid Assets Status      
================================
library:
  currentTag:  kgrid-library-1.0.9
  latestTag:   kgrid-library-1.0.9
  description: Changed the publish feature
activator:
  currentTag:  kgrid-activator-1.0.1
  latestTag:   kgrid-activator-1.0.1
  description: Refactored the health endpoint
cpic-kos:
  currentTag:  1.5.0
  latestTag:   1.5.0
  description: Update the Codeine CYP2D6 recommendation object
cpic-kit:
  currentTag:  1.1.0
  latestTag:   v1.1.0
  description: This is the release for KGrid team internal review.
================================

* A new version of CPIC-Kit is available.
  You can download at https://github.com/kgrid-demos/cpic-kit/releases/download/v1.1.0/cpic-kit.zip

Starting KGrid CPIC Kit
...

Changes in the library, activator and the CPIC knowledge objects can be update by running npm install

Changes to the CPIC Kit itself will require that you download a new cpic-kit.zip file. the example below depicts the KGrid Assets Status when you need to download a new cpic-kit.zip.

Development

For CPIC Kit developers we have outlined the tools and techniques used to code, test and publish the CPIC Kit. Please see details in the Developer Readme

Last Updated: 10/16/2018, 9:08:54 PM