MaveDB 2024: a curated community database with over seven million variant effects from multiplexed functional assays

Alan F Rubin^{1

2}, Jeremy Stone³, Aisha Haley Bianchi⁴, Benjamin J Capodanno³, Estelle Y Da⁵, Mafalda Dias^{6

7}, Daniel Esposito⁵, Jonathan Frazer^{6

7}, Yunfan Fu^{5

8}, Sally B Grindstaff³, Matthew R Harrington⁴, Iris Li⁵, Abbye E McEwen^{3

4

9}, Joseph K Min⁴, Nick Moore⁵, Olivia G Moscatelli^{8

10}, Jesslyn Ong^{10

11}, Polina V Polunina¹², Joshua E Rollins¹³, Nathan J Rollins¹⁴, Ashley E Snyder³, Amy Tam¹⁵, Matthew J Wakefield^{5

8

16}, Shenyi Sunny Ye⁴, Lea M Starita^{3

4}, Vanessa L Bryant^{8

10

17}, Debora S Marks^{18

19}, Douglas M Fowler^{20

21

22}

Affiliations

¹ Bioinformatics Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Australia. alan.rubin@wehi.edu.au.
² Department of Medical Biology, University of Melbourne, Parkville, Australia. alan.rubin@wehi.edu.au.
³ Brotman Baty Institute for Precision Medicine, Seattle, USA.
⁴ Department of Genome Sciences, University of Washington, Seattle, USA.
⁵ Bioinformatics Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
⁶ Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain.
⁷ University Pompeu Fabra, Barcelona, Spain.
⁸ Department of Medical Biology, University of Melbourne, Parkville, Australia.
⁹ Department of Laboratory Medicine and Pathology, University of Washington, Seattle, USA.
¹⁰ Immunology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
¹¹ Department of Microbiology and Immunology, University of Melbourne, Parkville, Australia.
¹² Bioinformatics Group, Department of Computer Science, University of Freiburg, Freiburg, Germany.
¹³ Department of Computer Science, The Graduate Center, The City University of New York, New York, USA.
¹⁴ Seismic Therapeutics, Watertown, USA.
¹⁵ Department of Systems Biology, Harvard Medical School, Boston, USA.
¹⁶ Department of Obstetrics, Gynaecology and Newborn Health, University of Melbourne, Parkville, Australia.
¹⁷ Department of Clinical Immunology & Allergy, The Royal Melbourne Hospital, Parkville, Australia.
¹⁸ Department of Systems Biology, Harvard Medical School, Boston, USA. debbie@hms.harvard.edu.
¹⁹ Broad Institute of Harvard and MIT, Boston, USA. debbie@hms.harvard.edu.
²⁰ Brotman Baty Institute for Precision Medicine, Seattle, USA. dfowler@uw.edu.
²¹ Department of Genome Sciences, University of Washington, Seattle, USA. dfowler@uw.edu.
²² Department of Bioengineering, University of Washington, Seattle, USA. dfowler@uw.edu.

PMID: 39838450
PMCID: PMC11753097
DOI: 10.1186/s13059-025-03476-y

MaveDB 2024: a curated community database with over seven million variant effects from multiplexed functional assays

Alan F Rubin et al. Genome Biol. 2025.

. 2025 Jan 21;26(1):13.

doi: 10.1186/s13059-025-03476-y.

Authors

Affiliations

¹ Bioinformatics Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Australia. alan.rubin@wehi.edu.au.
² Department of Medical Biology, University of Melbourne, Parkville, Australia. alan.rubin@wehi.edu.au.
³ Brotman Baty Institute for Precision Medicine, Seattle, USA.
⁴ Department of Genome Sciences, University of Washington, Seattle, USA.
⁵ Bioinformatics Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
⁶ Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain.
⁷ University Pompeu Fabra, Barcelona, Spain.
⁸ Department of Medical Biology, University of Melbourne, Parkville, Australia.
⁹ Department of Laboratory Medicine and Pathology, University of Washington, Seattle, USA.
¹⁰ Immunology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
¹¹ Department of Microbiology and Immunology, University of Melbourne, Parkville, Australia.
¹² Bioinformatics Group, Department of Computer Science, University of Freiburg, Freiburg, Germany.
¹³ Department of Computer Science, The Graduate Center, The City University of New York, New York, USA.
¹⁴ Seismic Therapeutics, Watertown, USA.
¹⁵ Department of Systems Biology, Harvard Medical School, Boston, USA.
¹⁶ Department of Obstetrics, Gynaecology and Newborn Health, University of Melbourne, Parkville, Australia.
¹⁷ Department of Clinical Immunology & Allergy, The Royal Melbourne Hospital, Parkville, Australia.
¹⁸ Department of Systems Biology, Harvard Medical School, Boston, USA. debbie@hms.harvard.edu.
¹⁹ Broad Institute of Harvard and MIT, Boston, USA. debbie@hms.harvard.edu.
²⁰ Brotman Baty Institute for Precision Medicine, Seattle, USA. dfowler@uw.edu.
²¹ Department of Genome Sciences, University of Washington, Seattle, USA. dfowler@uw.edu.
²² Department of Bioengineering, University of Washington, Seattle, USA. dfowler@uw.edu.

PMID: 39838450
PMCID: PMC11753097
DOI: 10.1186/s13059-025-03476-y

Abstract

Multiplexed assays of variant effect (MAVEs) are a critical tool for researchers and clinicians to understand genetic variants. Here we describe the 2024 update to MaveDB ( https://www.mavedb.org/ ) with four key improvements to the MAVE community's database of record: more available data including over 7 million variant effect measurements, an improved data model supporting assays such as saturation genome editing, new built-in exploration and visualization tools, and powerful APIs for data federation and streamlined submission and access. Together these changes support MaveDB's role as a hub for the analysis and dissemination of MAVEs now and into the future.

Keywords: DMS; Deep mutational scanning; Functional genomics; MAVEs; Multiplexed assays of variant effect; Variant classification.

PubMed Disclaimer

Conflict of interest statement

Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: NJR is employed by Seismic Therapeutics. DSM participates in an advisory role for Dyno Therapeutics, Octant Bio, Jura Bio, Tectonic Therapeutic, and Seismic Therapeutics.

Figures

**Fig. 1**
MaveDB contents as of November 2024. A Growth of the database by year. The bars show the cumulative number of datasets and the green line shows the cumulative number of variant effect measurements. B Diversity of target sequences. NCBI Taxonomy IDs were assigned and grouped according to the categories shown

**Fig. 2**
Example of a meta-analysis score set. The cartoon uses a real-world dataset to illustrate the relationship between experiment sets, experiments, score sets, and meta-analysis score sets. The results from two assays performed on the gene *NUDT15* were combined into a resulting “function score” that summarized performance across both assays [40]

**Fig. 3**
MaveDB web interface screenshots. A Score set visualizations. Score set pages now feature automatically generated visualizations, including a score histogram and variant effect heatmap. For non-coding targets, the heatmap is displayed at the nucleotide level. B Search page. The interface includes target sequence-based filters at the top, and listings for each matching experiment and its score sets in the main body of the page. MaveDB also supports filtering on publication information such as author via the “Publication filters” tab. C Score set creation. Users contributing score sets via the web form can follow this step-by-step workflow with embedded documentation

See this image and copyright information in PMC

References

1. Chen S, Francioli LC, Goodrich JK, Collins RL, Kanai M, Wang Q, et al. A genomic mutational constraint map using variation in 76,156 human genomes. Nature. 2024;625:92–100. - PMC - PubMed
1. Landrum MJ, Lee JM, Benson M, Brown GR, Chao C, Chitipiralla S, et al. ClinVar: improving access to variant interpretations and supporting evidence. Nucleic Acids Res. 2018;46:D1062–7. - PMC - PubMed
1. Fowler DM, Rehm HL. Will variants of uncertain significance still exist in 2030? Am J Hum Genet. 2024;111:5–10. - PMC - PubMed
1. Starita LM, Ahituv N, Dunham MJ, Kitzman JO, Roth FP, Seelig G, et al. Variant interpretation: functional assays to the rescue. Am J Hum Genet. 2017;101:315–25. - PMC - PubMed
1. Tabet D, Parikh V, Mali P, Roth FP, Claussnitzer M. Scalable functional assays for the interpretation of human genetic variation. Annu Rev Genet. 2022;56:441–65. - PubMed

MeSH terms

Actions
Actions
Actions
Actions
Actions

Grants and funding

LinkOut - more resources

Full Text Sources
- BioMed Central
- PubMed Central

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

MaveDB 2024: a curated community database with over seven million variant effects from multiplexed functional assays

Affiliations

MaveDB 2024: a curated community database with over seven million variant effects from multiplexed functional assays

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources