ga4gh.org

Collaborative Brainstorming for the Next Phase of GA4GH Implementation Forum Activities

Mallory Freeberg, Neerjah Skantharajah, & Guests

ga4gh.org

Code of Ethics and Community Conduct

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• Disrespectful communication and any other behaviours that lead to hostile environment

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The following will NOT be tolerated:

Read the full CECC on our website

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ga4gh.org/code-of-conduct

Read the Guidelines for Respectful Behaviour

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bit.ly/ga4gh-respectful-

engagement

Have questions or want to report? Contact Safe GA4GH Officer Paula Brantner at

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conduct@ga4gh.org

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Participating in a Hybrid Meeting

In Person

Virtual

Please use the handheld microphone closest to you. If there isn’t one nearby, simply raise your hand, and a GA4GH staff member will bring one to you.

Use the chat function for relevant comments

Neerjah will be your in-person representative, relaying questions and comments from virtual attendees.

Use the raise hand function to request the floor—wait to be called on before speaking.

“My name is <name> from <affiliation>”

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1.0 Introduction

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1.1 Welcome & Agenda

Link to the full agenda

Collaborative Brainstorming for the Next Phase of GA4GH Implementation Forum Activities

ga4gh.org

1.2 GIF Initiatives Review of 2024

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• Renewed GIF Charter
• Open call for new GIF Projects
• Launch of GIF AMA Program
• Updated GIF webpages

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“building networks of knowledge instead of silos of expertise”

ga4gh.org

1.2 GIF Initiatives Review of 2024

Renewed GIF Charter

2025+

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Annual review

Q4 2024

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Published on GA4GH website

Q3 2024

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Opened for public comment

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Q2 2024

Drafted new GIF Charter

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1.2 GIF Initiatives Review of 2024

Restarted GIF Projects

2025+

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Ongoing support

Q2 2025

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Accepted 2 new GIF Projects

Q1 2025

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Opened call for new projects

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Q3/4 2024

Reviewed current projects

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1.2 GIF Initiatives Review of 2024

Launched GIF AMA Program

2025+

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Host quarterly AMA events

Q1 2025

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Hosted 1st GIF AMA event

Q4 2024

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Opened for public comment

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Q2/3 2024

Drafted GIF AMA Program

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1.2 GIF Initiatives Review of 2024

• Any questions on GIF Initiatives so far?

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2.0 GIF “Ask Me Anything” (AMA) program

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2.1 GIF AMA program description

GIF AMA Events

• Interactive, virtual events
• Co-hosted by GIF leadership at an existing GA4GH meeting
• Minimal presentations
• Maximum time for Q&A which are subsequently disseminated

GIF AMA Resources

• Outputs of AMA events captured and shared publicly
• Address timezone challenges
• Seed living knowledge base maintained by the community

“facilitate exchange of practical knowledge, support collaborative learning, & create an inclusive space for networking & shared expertise”

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2.1 First GIF AMA event: Beacon

• 46 attendees (~3x typical attendance)
• 16 Qs asked & answered in 40’ (verbal & written)
• GA4GH webpage captures all materials (slides, recording, links) and questions & answers

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2.1 First GIF AMA event: Initial attendee feedback

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2.1 First GIF AMA event: Beacon Leads feedback

What went well

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What to change for future AMAs

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What was the impact

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2.1 First GIF AMA event: Attendee feedback

Did you attend the GIF AMA Beacon event?

Any feedback?

ga4gh.org

2.2 GIF AMAs: Open Brainstorm

• What GA4GH products would you like to have a GIF AMA in 2025?
• What do you think about the GIF AMA format?
• What do you think of the approach for sharing GIF AMA outcomes (i.e. capturing Q&As, sharing recording and transcript)?
• Any other general feedback on the GIF AMA program?

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3.0 GIF Projects

Lightning pitches

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3.1 Current GIF Project: Federated VLM

• Targeting rare disease variant interpretation use case
• Monthly open meetings 4th Thu 8 am EST
• 3 connected nodes using Beacon v2 API and tokens
• Network switching to Auth0 for authentication removing need for sites to exchange tokens - rationale
• Draft documentation in development
• VLM Website here
• VLM Vision Statement here
• VLM Technical Specification Document here
• VLM Service Agreement here
• VLM User Agreement here

VariantMatcher �(JHU)�Node 1

Franklin�(Genoox)

Node 2

Geno2MP/�MyGene2

(UWashington)

Node 3

Seqr� (Broad)�Node 4

Best Practices

Stay in touch

ga4gh.org

3.2 eLwazi - Background and Motivation

• Genetic diversity: African populations possess the most extensive range of genetic variation worldwide
• Underrepresentation in reference panels: Existing imputation resources built on mostly European data often fail to capture African-specific variants and complex substructures
• Rationale for population-specific methods: Tailored approaches increase accuracy, revealing vital low-frequency alleles relevant to disease risk and personalized medicine
• Federated approach: Enables geographically distributed groups to collaborate securely, respecting regional privacy restrictions and pooling diverse data for more robust imputation models

ga4gh.org

3.2 eLwazi - Existing Imputation Services

Challenges

• Different tools (e.g PWT, Minimac4, Impute5)
• Reference panels
• Private
• Size
• Results
• Different APIs
• Different encryptions
• Size

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3.2 eLwazi - Federated Imputation approach

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3.2 eLwazi - federated analysis infrastructure

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3.2 eLwazi - Progress to-date

• Replaced the WES starter kit with WESkit,
• Added a DRS resolver to WESkit,
• Currently replacing DRS starter-kit with Gen3 implementation,
• Exploring potential GA4GH standards to include (Testbeds, Crypt4GH, TES),
• Developing a dashboard

ga4gh.org

3.2 eLwazi - Challenges / Questions

• Recommendation on transitioning from starterkits or pilot to production?
• Maturity level, security considerations …
• What would be the best way of handling multiple outputs/inputs?
• Input:
• 1..n VCF files (and paired index files)
• Output
• 1..n VCF files (and paired index files, paired score files)
• 1..n PDF reports
• The number of inputs/outputs is variable. One option seems to be to collect these into Compound Objects. Is this a reasonable approach?

ga4gh.org

3.3 Cloud-Based BRCA Exchange Variant Analysis Environment Using GA4GH Standards

Data repository

Interactive analysis environment

ga4gh.org

3.3 Cloud-Based BRCA Exchange Variant Analysis Environment Using GA4GH Standards

Modern data tooling

• Distributed data frames
• Object storage

Standards

• GKS
• DRS
• WES

Popular tools

• VEP/SnpEff
• R/Bioconductor
• Pandas
• Matplotlib/ggplot
• … your favorite?

Camber Stash

ga4gh.org

3.3 Cloud-Based BRCA Exchange Variant Analysis Environment Using GA4GH Standards

Interactive analysis using metadata standards

Batch jobs as reusable Science Apps

ga4gh.org

3.3 Cloud-Based BRCA Exchange Variant Analysis Environment Using GA4GH Standards

• BRCA analysis environment
• Variants identified using GKS
• Datasets available via DRS
• Science Apps shared via TRS

ga4gh.org

3.3 Cloud-Based BRCA Exchange Variant Analysis Environment Using GA4GH Standards

Annotate BRCA variants using new tools

Train ML models based on curated variant data

Create Science Apps usable by biologists

Easily share data and analysis environments

Publish new workflows and tooling

Use Cases

ga4gh.org

3.3 Cloud-Based BRCA Exchange Variant Analysis Environment Using GA4GH Standards

Suggest use cases

Tell us about your favorite tool

Point us to other datasets or genes of interest

Sign up to try it out!

Offer standards and reference implementations

Get Involved!

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🛠️

🧑‍💻

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https://tinyurl.com/variant-analysis

ga4gh.org

3.4 Trusted Research Environment (TRE) Open Suite

GIF: TRE Open Suite

Pavel Nikonorov¹ , Muhammad Usama Sardar², Alex Kanitz^3,4

[1] GENXT; [2] TU Dresden Germany; [3] Pacific Analytics�[4] Swiss Institute of Bioinformatics / ELIXIR Switzerland

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ga4gh.org

What is a TRE?

TREs make sensitive biomedical data actionable -�without compromising privacy or compliance!

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3.4. TRE Open Suite | Pavel, Usama & Alex

“Trusted Research Environments (TREs) are highly secure and controlled computing environments that allow approved researchers from authorised organisations a safe way to access, store, and analyse sensitive data remotely.”

Hadley Sheppard, Lifebit

ga4gh.org

What problems are we facing?

• TREs are hard to build
• Complex technical & legal requirements
• TREs are hard to migrate
• Definitions & requirements differ across jurisdictions
• TREs are hard to federate
• Lack of interoperability, trust issues

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3.4. TRE Open Suite | Pavel, Usama & Alex

ga4gh.org

Why this GIF Project?

Questions we would like to answer:

1. Can we build TREs
2. Can we modularise TRE builds
3. Can we federate TREs

using GA4GH products?

3.4. TRE Open Suite | Pavel, Usama & Alex

ga4gh.org

Main Deliverables (ideas, subject to change)

1. Open Framework
• Describes workload execution flow and necessary interfaces for TRE discovery, dynamic provisioning, federation, trust relationships, and the application & formal verification of data security & privacy preserving technologies
• Incorporates available & emerging policies (e.g., SARTRE, EOSC-ENTRUST)
2. Toolbox
• Plugins for operationalising different data security & privacy enhancing technologies (e.g., Crypt4GH, Confidential Computing, Differential Privacy, Homomorphic Encryption)
• Auxiliary tooling for policy interpretation, trust assurances, federation, etc.

3.4. TRE Open Suite | Pavel, Usama & Alex

ga4gh.org

Open Framework: Policy in, TRE* out

Researcher /�scheduler

Job

Applicable policies

Machine-readable policy

Technical requirements

TRE in the network

Provision on-demand

Job

execution

TRE Open Suite

3.4. TRE Open Suite | Pavel, Usama & Alex

* Core tech stack only

ga4gh.org

Toolbox: Building modular TREs

Middlewares

Servers

Clients

Component framework

• GA4GH-SDK
• ELIXIR Cloud Components

• C4GH-TES
• Confido

• proTES
• TESK
• Funnel
• TES-on-Azure

3.4. TRE Open Suite | Pavel, Usama & Alex

Groundwork / examples

ga4gh.org

Call to Action

https://tinyurl.com/open-tre-suite

Expression of Interest

3.4. TRE Open Suite | Pavel, Usama & Alex

#gif-open-tre

ga4gh.org

3.5 GIF Projects: Open Brainstorm

• Do you have suggestions for projects or people to connect with to support a particular GIF Project?
• Do you have any experiences to share related to the GIF Projects who presented?
• Any general feedback on GIF Projects?

ga4gh.org

4.0 GIF Priorities & Wrap-up

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4.1 GIF Activities Prioritisation

At the end of the session you will be asked to pick 3-5 activities that you think GIF should prioritise next.

Before we share the feedback form, here are the possible activities…

ga4gh.org

4.1 GIF Activities Prioritisation

- Host more GIF AMA events in the format they are now

- Adapt GIF AMA format to support different needs

- Make GIF AMA resources more accessible (e.g. Qs&As, recordings)

- Raise awareness of existing GIF Projects and how to get involved

- Support more GIF Projects

- GIF representation at more GA4GH meetings (e.g. CoI, WS, Working Group)

- Provide direct feedback on other GA4GH work related to implementation (e.g. TASC activities, best practices)

- Develop the GA4GH Community of Practice framework

- Host new GIF-specific meetings on relevant topics to the GA4GH Community

- Raise awareness of current GA4GH implementation successes and impact

- Host session at every GA4GH Connect

- Provide GIF updates at every GA4GH Plenary

ga4gh.org

4.2 Feedback on GIF Activities Prioritisation

Feedback survey

Please complete now or by 10th April 2025

Aggregated results will be shared

bit.ly/GIF_feedback

ga4gh.org

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4.3 Nominations for GIF Co-Lead

https://www.ga4gh.org/open_call/ga4gh-implementation-forum-gif-co-lead/

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4.3 Thank you!

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Break time

3:45 PM to 4:00 PM

Lobby

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