Quick Start

⏱ tutorial time: 10 minutes

The Isabl Platform is freely available for research and academic purposes. For commercial use, a license is required. To access the source code, please get in touch with us.

Welcome to the 10 Minutes to Isabl guide! This tutorial will walk you through installation, meta data registration, data import, and automated data processing.

• Also check the Retrieve Data and Register Metadata guides!

• Join us on Gitter if you have questions

• Submit an issue 🐛 if you are having problems with this guide

Intro to Isabl

Checkout the documentation home page for an intro to Isabl.

Isabl is composed of a patient centric relational model, a web-based metadata architecture, and a command line client.

Prerequisites

• Docker Compose for building and running the application.

Make sure your installation doesn't require sudo to run docker and docker-compose. Otherwise you will have issues running this demo. Check docker run hello-world runs without problem. If you have permissions issues, see how to run docker as-non-root user.

Demo Setup

Let's start by clone the demo:

git clone https://github.com/papaemmelab/isabl_demo.git --recurse-submodules
cd isabl_demo

Make sure the git submodule folders isabl_api and isabl_cli are not empty. If they are, probably the --recurse-submodules flag didn't work.

As a workaround, run:

git submodule update --recursive --init

Next, source a simple initiation profile:

source .demo-profile

If you are redoing the tutorial, we recommend to remove the demo directory and clone it again:

chmod -R u+w isabl_demo && rm -rf isabl_demo

Also remove the Docker volume:

docker volume rm isabl_demo_local_postgres_data

Installation

This installation relies on docker private images. Please make sure with the isabl team admins that you have proper access to them.

Build and run the application (this might take a few minutes):

Before running docker-compose build, specify your platform architecture if it's different from the standard intel linux/amd64, i.e. you have an Apple M1/M2:

export DOCKER_DEFAULT_PLATFORM=linux/arm64

If you are not sure, you can check your platform by running:

uname -m

demo-compose build

Now we can run the application in the background:

demo-compose up -d

You can type demo-compose down to stop the application. And use demo-compose logs -f in a new session to see logs.

Create a superuser by running demo-django createsuperuser, for example using credentials: username=admin password=admin email=[e-mail]

Now, visit http://localhost:8000/ and log in!

demo-compose, demo-django, and demo-cli are simple wrappers around docker-compose - check them out. The isabl_demo directory was bootstrapped using cookiecutter-isabl, a proud fork of cookiecutter-django! Many topics from their guide will be relevant to your project.

Create Project

Creating a project in Isabl is as simple as adding a title. You can also specify optional fields:

Hover over the menu and click in the + icon to add a new project.

Configure Isabl CLI

We need to let isabl-cli know where can the API be reached, and what CLI settings we should use (if you are using demo-compose, these variables are already set):

# install isabl-cli from github (Use a virtualenv as a good practice)
pip install -e ./isabl_cli
pip install -e ./isabl_apps

# point to your API URL
export ISABL_API_URL=http://localhost:8000/api/v1/

# set environment variable for demo client
export ISABL_CLIENT_ID="demo-cli-client"

Now we can create a client for isabl-cli:

# create and update the client object
demo-cli python3.6 ./assets/metadata/create_cli_client.py

# check the file used to create the client
cat ./assets/metadata/create_cli_client.py

Register Samples

Before we create samples, let's use isabl-cli to add choices for Center, Disease, Sequencing Technique, and Data Generating Platform:

demo-cli python3.6 ./assets/metadata/create_choices.py

New options can also be easily created using the admin site: http://localhost:8000/admin/

We will use Excel submissions to register samples through the web interface. To do so, the demo project comes with a pre-filled metadata form available at:

open assets/metadata/demo_submission.xlsm

When prompted to allow macros, say yes. This will enable you to toggle between optional and required columns. By the way, Isabl has multiple mechanisms for metadata ingestion! Learn more here.

Now let's proceed to submit this excel form. First open the directory:

open assets/metadata

And drag the demo_submission.xlsm file into the submit samples form:

Click the + button in the project panel header to add new samples.

We can also review metadata at the command line:

isabl get-metadata experiments --fx

Expand and navigate with arrow keys, press e to expand all and E to minimize. Learn more at fx documentation. Use --help to learn about other ways to visualize metadata (e.g. tsv).

For this particular demo, we wanted to create a sample tree that showcased the flexibility of Isabl's data model. Our demo individual has two samples, one normal and one tumor. The tumor sample is further divided into two biological replicates (or aliquots), with two experiments conducted on the second aliquot:

A data generation process tree that resulted in 4 sequencing experiments (or ultimately bams), produced from two samples of the same individual.

RESTful API

Although not required for this tutorial, you are welcome to checkout the RESTful API documentation at: http://localhost:8000/api/v1/ or https://isabl.github.io/redoc/.

Import Reference Data

Given that isabl-cli will move our test data, let's copy original assets into a staging directory:

mkdir -p assets/staging && cp -r assets/data/* assets/staging

Now let's import the genome:

demo-isabl import-reference-genome \
    --assembly GRCh37 \
    --genome-path assets/staging/reference/reference.fasta

We can also import BED files for our demo Sequencing Technique:

demo-isabl import-bedfiles \
    --technique DEMO_TECHNIQUE \
    --targets-path assets/staging/bed/targets.bed \
    --baits-path assets/staging/bed/baits.bed \
    --assembly GRCh37 \
    --species HUMAN \
    --description "Demo BED files"

Check that import was successful:

isabl get-bed DEMO_TECHNIQUE  # retrieve BED file
isabl get-reference GRCh37    # retrieve reference genome

By means of the --data-id flag, the command get-reference also allows you to retrieve the indexes generated during import. To get a list of available files per assembly run:

isabl get-reference GRCh37 --resources

Learn more about importing data into Isabl here.

On this previous steps of the demo, we used demo-isabl to import references and bedfiles, because it is a wrapper to run isabl inside a container with samtools, bwa and tabix . These tools are needed to index these imported genomic files.

Import Experimental Data

Next step is to import data for the samples we just created:

isabl import-data \
    -di ./assets/staging            `# provide data location ` \
    -id identifier                  `# match files using experiment id` \
    -fi identifier.contains "demo"  `# filter samples to be imported ` \
    --symlink                       `# to not move the original demo data`

Add --commit to complete the operation.

Retrieve imported data for the normal to see how directories are created:

isabl get-data -fi sample.identifier "demo normal"

The front end will also reflect that data has been imported.

Writing Applications

Isabl is a language agnostic platform and can deploy any pipeline. To get started, we will use some applications from isabl-io/apps. Precisely we will run alignment, quality control, and variant calling. Applications were previously registered in client object. Once registered, they are available in the client:

isabl apps-grch37

Learn more about customizing your instance with Isabl Settings.

First we'll run alignment (pass --commit to deploy):

isabl apps-grch37           `# apps are grouped by assembly ` \
    bwa-mem-0.7.17.r1188    `# run bwa-mem version 0.7.17.r1188 ` \
    -fi tags.contains data  `# filter using tags, feel free to try others `

Note that if you try to re-run the same command, Isabl will notify you that results are already available. If for some reason the analyses fail, you can force a re-run using --force.

Now we can retrieve bams from the command line:

isabl get-bams -fi sample.individual.identifier "demo individual"

We can also visualize aligned bams online:

Insert 2:123,028-123,995 in the locus bar, that's were our test data has reads. Learn more about default BAMs in the Writing Applications guide.

Although the BAM file is an output of the bwa-mem analysis, Isabl enables registering default bams to an experiment. Thus a link is available in the sample panel.

Auto-merge Analyses

Let's get some stats for our experiments with a quality control application:

isabl apps-grch37 qc-data-0.1.0 -fi identifier.icontains demo --commit

This quality control application has defined logic to merge results at a project and individual level. Upon completion of analyses execution, Isabl automatically runs the auto-merge logic:

A short message is displayed at the end of the run indicating merge analyses are being run.

Isabl-web can render multiple types of results, in this case we will check at HTML reports. Results for our qc-data application are available at an experiment, individual, and project level. In this example we are looking at the project-level auto-merge analysis:

A project level Quality Control report. Can you find the Experiment and Individual-level reports?

Applications can define any custom logic to merge analyses.

Multi-experiment Analyses

Up until now we've run applications that are linked to one experiment only. However, analyses can be related to any number of target and reference experiments. For example this implementation of Strelka uses tumor-normal pairs. Before you can run this command you will need to retrieve the system id of your experiments, let's try:

isabl get-metadata experiments -f system_id

Now insert those identifiers in the following command:

isabl apps-grch37 strelka-2.9.1 \
    --pairs {TUMOR 1 ID} {NORMAL ID}  `# replace tumor 1 system id and normal system id` \
    --pairs {TUMOR 2 ID} {NORMAL ID}  `# replace tumor 2 system id and normal system id` \
    --pairs {TUMOR 3 ID} {NORMAL ID}  `# replace tumor 3 system id and normal system id`

You can retrieve registered results for the analysis, for instance the indels VCF:

isabl get-results -fi name STRELKA --result-key indels

To find out what other results are available use:

# app-primary-key can be retrieved from the frontend
isabl get-results --app-results {app-primary-key}

# when writing this tutorial, the app key for strelka was 5
isabl get-results --app-results 5

Furthermore, you can get paths for any instance in the database using get-paths:

isabl get-outdirs -fi name STRELKA

Lastly, lets check the indels VCFs through the web portal:

Software Development Kit

To finalize the tutorial, we'll use Isabl as an SDK with ipython:

# we'll access ipython using the cli container
demo-cli ipython

Then lets check the output directories of Strelka:

import isabl_cli as ii

# retrieve analyses from API using filters
analyses = ii.get_analyses(name="STRELKA")

# list the strelka ouput directories
for i in analyses:
    !ls {i.storage_url}/strelka

The analysis objects are Munch, in other words they are dot-dicts (like javascript):

analysis = analyses[0]

# get the target experiment or tumor
target = analysis.targets[0]

# print the parent sample class
print(target.sample.category)

# see available fields
print(target.keys())

Wrap up and Next Steps

Learn about CLI advanced configuration to customize functionality:

Isabl Settings

Learn about writing applications:

Writing Applications

Ready for production? learn more about deployment:

Production Deployment