The concept of a genomics “Beacon” refers to facilitating connection between genomic data suppliers, developers, and researchers interested in acquiring genetic variation data. The Beacon system was intended to be simple: an API that allows users to query genomic data collections for the presence of specified genetic variations and receive a simple “Yes” or “No” response. The term “Beacon” was chosen to represent the goal of illuminating the hitherto opaque world of genetic data sharing through widespread engagement.The Beacon Project, which became one of the initial Global Alliance for Genomics and Health (GA4GH) Driver Projects, was warmly welcomed by both members of the GA4GH developer community and genomic resource providers Rambla et al. 2022.

By 2016, over 35 institutions worldwide had adopted the Beacon protocol across more than 90 genomic datasets. At this point, ELIXIR, the European bioinformatics infrastructure organization, became interested in moving the community initiative toward a defined definition. Their efforts were focused on improving usability in order to encourage wider adoption of the Beacon system within the biomedical genomics industry.

The Beacon v1.0 protocol was formally accepted as a GA4GH standard in 2018 Fiume et al. 2019. Although this version included some new features, such as limited support for structural variant inquiries, quantitative replies, and interaction with external protocols, it mostly stuck to the basic idea of querying variations and obtaining aggregate results. However, it quickly became clear that the procedure required significant extension, particularly to fulfill the objectives of clinical applications in rare disease and cancer genomics. This understanding prompted the start of the Beacon v2 design process, which attempted to reconfigure the protocol to support a wider range of use cases.

Copy number variations (CNVs) are genomic segments with different numbers of copies. These variations, which include both DNA sequence amplifications and deletions, have been found in every domain of life, including bacteria, archaea, plants, and mammals. CNVs contribute significantly to genomic variety and can play an important role in promoting fast adaptive evolution, as well as the development of inherited and somatic human illnesses such as cancer Lauer and Gresham 2019.

Subsequently, The classification of CNV gains and losses into more specific categories: copy number gain, low-level copy number gain, high-level copy number gain, focal genome amplification, copy number loss, low-level copy number loss, high-level copy number loss, and complete genomic deletion. This detailed categorization enhances the precision in identifying and describing CNVs. More information can be found on the ELIXIR hCNVs resource page.

In this tutorial, we will utilize the Beacon2 Query tool to explore a Beacon built using data from hg38_altaware_nohla-cnv-anchored to identify Copy Number Variants (CNVs). Additionally, we will perform queries on the same dataset using various search terms to locate specific data points, demonstrating the tool’s versatility and effectiveness in genomic data exploration.

Agenda

In this tutorial, we will cover:

1. Querying the Entire Database Collection for CNVs Without Specifying Genomic Location
2. Querying the Entire Database Collection for CNVs at a Specific Genomic Location
3. Conclusion

Querying the Entire Database Collection for CNVs Without Specifying Genomic Location

We will perform a simple query to identify reads that match the “VARIANT STATE”: copy number gain

Hands-on: Query the Beacon MongoDB

1. Use Beacon2 CNV ( Galaxy version 2.1.1+galaxy0) to query the Beacon genomicVariations collection
   • “DATABASE HOST”: 20.108.51.167
   • “DATABASE PORT”: 27017
   • “DATABASE”: beacon
   • “COLLECTION”: genomicVariations
   • ““VARIANT STATE”“: copy number gain

The search function will query the Beacon database and display the results that match our specified criteria.

Question

What dose variantId “EFO:0030070” means?

{'_id': ObjectId('66ab66797f2ec2a3f3484ed3'),
'assemblyId': 'GRCh38',
'biosampleId': 'HG00103',
'definitions': {'Location': {'chromosome': '1',
                             'end': 16728256,
                             'start': 16716711}},
'id': 'refvar-66ab66797f2ec2a3f3484ed3',
'info': {'cnCount': 4,
         'cnValue': 2.17226,
         'legacyId': 'DRAGEN:GAIN:chr1:16716712-16728256'},
'updated': '2024-08-01T10:42:58.106345',
'variantInternalId': 'chr1:16716711-16728256:EFO:0030070',
'variantState': {'id': 'EFO:0030070', 'label': 'copy number gain'}}

Solution

EFO:0030069 is a term used to describe the copy number gain. The term was set by the CNV community. For more information go to the CNV annotation formats

Querying the Entire Database Collection for CNVs at a Specific Genomic Location

We will perform a targeted query to identify reads that match the “VARIANT STATE”: copy number gain on Chromosome 20starting at position 29313239 and ending at 29340136

Hands-on: Query the Beacon MongoDB

1. Use Beacon2 CNV ( Galaxy version 2.1.1+galaxy0) to query the Beacon genomicVariations collection
   • “DATABASE HOST”: 20.108.51.167
   • “DATABASE PORT”: 27017
   • “DATABASE”: beacon
   • “COLLECTION”: genomicVariations
   • “CHROMOSOME”: 20
   • “START”: 29313239
   • “END”: 29340136
   • ““VARIANT STATE”“: copy number gain

This query will generate a list of all reads that meet the specified parameters, matching the “VARIANT STATE” of copy number gain on Chromosome 20, within the defined range from position 29313239 to 29340136.

In this tutorial, we used our testing Beacon server. To query a specific Beacon, update your credentials in the Galaxy user preferences and enter your server’s details by adjusting the “DATABASE HOST” and “DATABASE PORT” fields accordingly.

Comment: Use Credentials to Access Specific Beacon

1. Make sure you are logged in to Galaxy.
2. Go to User > Preferences in the top menu bar.
3. To add beacon database credentials, click on Manage Information and fill in the Beacon2 Account empty fields db_auth_source, db_user and db_password.
4. Make the changes and click on the Save button at the bottom.

Conclusion

Now, you have a general knowledge of Beacons and how to query them.

You can apply what you learned in this tutorial to query Beacon made by your institution or other institutions.

We hope you find this tutorial helpful!

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Key points

• Understanding Beacon Databases involves grasping their purpose and significance in genomic research and data sharing.

• Mastering the Beacon2 CNV Tool includes developing skills to effectively query and analyze specific CNVs within the Beacon2 database.

• Efficient Querying for CNVs focuses on accurate data retrieval and precise query formulation using the Beacon2 tool.

• Hands-On Application provides practical experience in querying Beacons, ensuring data integrity, and troubleshooting queries.

• Recognizing the Importance of CNVs highlights the role of CNVs in genetic variation and their relevance in research using Beacon databases.

Frequently Asked Questions

Useful literature

Further information, including links to documentation and original publications, regarding the tools, analysis techniques and the interpretation of results described in this tutorial can be found here.

References

1. Fiume, M., M. Cupak, S. Keenan, J. Rambla, S. de la Torre et al., 2019 Federated discovery and sharing of genomic data using Beacons. Nature Biotechnology 37: 220–224. 10.1038/s41587-019-0046-x
2. Lauer, S., and D. Gresham, 2019 An evolving view of copy number variants. Current Genetics 65: 1287–1295. 10.1007/s00294-019-00980-0
3. Rambla, J., M. Baudis, R. Ariosa, T. Beck, L. A. Fromont et al., 2022 Beacon v2 and Beacon networks: A “lingua franca” for federated data discovery in biomedical genomics, and beyond. Human Mutation. 10.1002/humu.24369

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Citing this Tutorial

1. Khaled Jum'ah, Krzysztof Poterlowicz, Querying a Beacon Database for Copy Number Variants (CNVs) (Galaxy Training Materials). https://training.galaxyproject.org/training-material/topics/variant-analysis/tutorials/beacon_cnv_query/tutorial.html Online; accessed TODAY
2. Hiltemann, Saskia, Rasche, Helena et al., 2023 Galaxy Training: A Powerful Framework for Teaching! PLOS Computational Biology 10.1371/journal.pcbi.1010752
3. Batut et al., 2018 Community-Driven Data Analysis Training for Biology Cell Systems 10.1016/j.cels.2018.05.012

BibTeX

@misc{variant-analysis-beacon_cnv_query,
author = "Khaled Jum'ah and Krzysztof Poterlowicz",
	title = "Querying a Beacon Database for Copy Number Variants (CNVs) (Galaxy Training Materials)",
	year = "",
	month = "",
	day = ""
	url = "\url{https://training.galaxyproject.org/training-material/topics/variant-analysis/tutorials/beacon_cnv_query/tutorial.html}",
	note = "[Online; accessed TODAY]"
}
@article{Hiltemann_2023,
	doi = {10.1371/journal.pcbi.1010752},
	url = {https://doi.org/10.1371%2Fjournal.pcbi.1010752},
	year = 2023,
	month = {jan},
	publisher = {Public Library of Science ({PLoS})},
	volume = {19},
	number = {1},
	pages = {e1010752},
	author = {Saskia Hiltemann and Helena Rasche and Simon Gladman and Hans-Rudolf Hotz and Delphine Larivi{\`{e}}re and Daniel Blankenberg and Pratik D. Jagtap and Thomas Wollmann and Anthony Bretaudeau and Nadia Gou{\'{e}} and Timothy J. Griffin and Coline Royaux and Yvan Le Bras and Subina Mehta and Anna Syme and Frederik Coppens and Bert Droesbeke and Nicola Soranzo and Wendi Bacon and Fotis Psomopoulos and Crist{\'{o}}bal Gallardo-Alba and John Davis and Melanie Christine Föll and Matthias Fahrner and Maria A. Doyle and Beatriz Serrano-Solano and Anne Claire Fouilloux and Peter van Heusden and Wolfgang Maier and Dave Clements and Florian Heyl and Björn Grüning and B{\'{e}}r{\'{e}}nice Batut and},
	editor = {Francis Ouellette},
	title = {Galaxy Training: A powerful framework for teaching!},
	journal = {PLoS Comput Biol} Computational Biology}
}

                   

Funding

These individuals or organisations provided funding support for the development of this resource

Go Further

Do you want to extend your knowledge? Follow one of our recommended follow-up trainings:

• tutorial Hands-on: Working with Beacon V2: A Comprehensive Guide to Creating, Uploading, and Searching for Variants with Beacons

Galaxy Administrators: Install the missing tools

You can use Ephemeris's shed-tools install command to install the tools used in this tutorial.

shed-tools install [-g GALAXY] [-a API_KEY] -t <(curl https://training.galaxyproject.org/training-material/api/topics/variant-analysis/tutorials/beacon_cnv_query/tutorial.json | jq .admin_install_yaml -r)

Alternatively you can copy and paste the following YAML

---
install_tool_dependencies: true
install_repository_dependencies: true
install_resolver_dependencies: true
tools: []

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