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Peer-reviewedCC BY 4.0Nucleic Acids Research

VarNexus: an integrative database for interpreting disease-associated regulatory variants through multimodal predictions and functional evidence

  1. 1Institutes of Biomedical Sciences, Inner Mongolia University , Hohhot 010070 ,
  2. 2College of Informatics, Huazhong Agricultural University , Wuhan 430070 ,
  3. 3State Key Laboratory of Genetic Engineering, National Clinical Research Center for Aging and Medicine, Huashan Hospital, Collaborative Innovation Center of Genetics and Development, Human Phenome Institute, Shanghai Engineering Research Center of Industrial Microorganisms, School of Life Sciences, Fudan University , Shanghai 200438 ,

Abstract

Genome-wide association studies (GWAS) have identified numerous loci associated with complex diseases and traits, yet the functional interpretation of non-coding risk variants remains challenging. Sequence-to-function models like AlphaGenome provide large-scale multi-modal predictions of variant effects, but their predictions lack direct experimental support. In contrast, empirical resources such as molecular quantitative trait loci (QTLs) and massively parallel reporter assays (MPRAs) offer population-based or experimental support for variant function, but suffer from limited genomic coverage. Here, we present VarNexus (https://biomed.imu.edu.cn/varnexus), an integrative resource for connecting disease-associated variants with predicted, population-based, and experimental evidence. VarNexus currently contains 230 404 fine-mapped candidate variants across 1891 disease-related phenotypes from UK Biobank and FinnGen. It integrates precomputed AlphaGenome predictions across 11 regulatory output types with bulk and single-cell xQTLs, MPRA measurements, and GWAS-eQTL colocalization results. VarNexus enables cross-linked searches by variant, phenotype, and gene, together with on-demand AlphaGenome prediction, multi-omics genome-browser visualization, and regulatory network exploration. By combining sequence-based predictions with population-based and experimental evidence, VarNexus provides a framework for prioritizing candidate regulatory mechanisms supported by multiple evidence layers.

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BibTeX
@article{gong2026varnexus,
  title = {{VarNexus: an integrative database for interpreting disease-associated regulatory variants through multimodal predictions and functional evidence}},
  author = {Lihai Gong and Cheng Tan and Jinhui Zhang and Rigan Shu and Shutong Guo and Tingting Xiao and Jialin Shi and Jing Wang and Ting Ni and Ruofan Ding},
  journal = {Nucleic Acids Research},
  year = {2026},
  month = oct,
  doi = {10.1093/nar/gkag1056},
  url = {https://academic.oup.com/nar/advance-article/doi/10.1093/nar/gkag1056/9002500},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - VarNexus: an integrative database for interpreting disease-associated regulatory variants through multimodal predictions and functional evidence
AU  - Lihai Gong
AU  - Cheng Tan
AU  - Jinhui Zhang
AU  - Rigan Shu
AU  - Shutong Guo
AU  - Tingting Xiao
AU  - Jialin Shi
AU  - Jing Wang
AU  - Ting Ni
AU  - Ruofan Ding
PY  - 2026
DA  - 2026/10/27
JO  - Nucleic Acids Research
DO  - 10.1093/nar/gkag1056
UR  - https://academic.oup.com/nar/advance-article/doi/10.1093/nar/gkag1056/9002500
AB  - Genome-wide association studies (GWAS) have identified numerous loci associated with complex diseases and traits, yet the functional interpretation of non-coding risk variants remains challenging. Sequence-to-function models like AlphaGenome provide large-scale multi-modal predictions of variant effects, but their predictions lack direct experimental support. In contrast, empirical resources such as molecular quantitative trait loci (QTLs) and massively parallel reporter assays (MPRAs) offer population-based or experimental support for variant function, but suffer from limited genomic coverage. Here, we present VarNexus (https://biomed.imu.edu.cn/varnexus), an integrative resource for connecting disease-associated variants with predicted, population-based, and experimental evidence. VarNexus currently contains 230 404 fine-mapped candidate variants across 1891 disease-related phenotypes from UK Biobank and FinnGen. It integrates precomputed AlphaGenome predictions across 11 regulatory output types with bulk and single-cell xQTLs, MPRA measurements, and GWAS-eQTL colocalization results. VarNexus enables cross-linked searches by variant, phenotype, and gene, together with on-demand AlphaGenome prediction, multi-omics genome-browser visualization, and regulatory network exploration. By combining sequence-based predictions with population-based and experimental evidence, VarNexus provides a framework for prioritizing candidate regulatory mechanisms supported by multiple evidence layers.
SN  - 0305-1048
SN  - 1362-4962
ER  -