HumanNet v2: human gene networks for disease research
Open accessAbstract
Human gene networks have proven useful in many aspects of disease research, with numerous network-based strategies developed for generating hypotheses about gene-disease-drug associations. The ability to predict and organize genes most relevant to a specific disease has proven especially important. We previously developed a human functional gene network, HumanNet, by integrating diverse types of omics data using Bayesian statistics framework and demonstrated its ability to retrieve disease genes. Here, we present HumanNet v2 (http://www.inetbio.org/humannet), a database of human gene networks, which was updated by incorporating new data types, extending data sources and improving network inference algorithms. HumanNet now comprises a hierarchy of human gene networks, allowing for more flexible incorporation of network information into studies. HumanNet performs well in ranking disease-linked gene sets with minimal literature-dependent biases. We observe that incorporating model organisms' protein-protein interactions does not markedly improve disease gene predictions, suggesting that many of the disease gene associations are now captured directly in human-derived datasets. With an improved interactive user interface for disease network analysis, we expect HumanNet will be a useful resource for network medicine.
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Gene interactions usually exist in the form of networks, such as gene regulatory networks and biological signaling pathways.
“Second, gene interactions usually exist in the form of networks (i.e., gene regulatory networks and biological signaling pathways) 43 , and this kind of prior knowledge hasn't been explicitly incorporated in scBERT.”
From scBERT as a Large-scale Pretrained Deep Language Model for Cell Type Annotation of Single-cell RNA-seq Data (2021) · cites this paper as [43]
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Cites
Structure, function and diversity of the healthy human microbiome
The Human Microbiome Project Consortium (2012) · Nature · doi:10.1038/nature11234 · Cited by 11,726 · see citing works
NCBI GEO: archive for functional genomics data sets—update
Barrett, T., Wilhite, S. E., Ledoux, P., Evangelista, C., Kim, I. F., Tomashevsky, M., Marshall, K. A., Phillippy, K. H., Sherman, P. M., Holko, M., et al. (2012) · Nucleic Acids Research · doi:10.1093/nar/gks1193 · Cited by 10,418 · see citing works
KEGG: new perspectives on genomes, pathways, diseases and drugs
Kanehisa, M., Furumichi, M., Tanabe, M., Sato, Y., & Morishima, K. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkw1092 · Cited by 8,865 · see citing works
Szklarczyk, D., Morris, J. H., Cook, H., Kuhn, M., Wyder, S., Simonovic, M., Santos, A., Doncheva, N. T., Roth, A., Bork, P., et al. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkw937 · Cited by 6,980 · see citing works
Network medicine: a network-based approach to human disease
Barabási, A.-L., Gulbahce, N., & Loscalzo, J. (2011) · Nature Reviews Genetics · doi:10.1038/nrg2918 · Cited by 5,034 · see citing works
Structure and function of the global ocean microbiome
Sunagawa, S., Coelho, L. P., Chaffron, S., Kultima, J. R., Labadie, K., Salazar, G., Djahanschiri, B., Zeller, G., Mende, D. R., Alberti, A., et al. (2015) · Science · doi:10.1126/science.1261359 · Cited by 2,945 · see citing works
The Reactome Pathway Knowledgebase
Fabregat, A., Jupe, S., Matthews, L. R., Sidiropoulos, K., Gillespie, M. E., Garapati, P. V., Haw, R., Jassal, B., Korninger, F., May, B., et al. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkx1132 · Cited by 2,798 · see citing works
Piñero, J., Bravo, À., Queralt-Rosinach, N., Gutiérrez-Sacristán, A., Deu-Pons, J., Centeno, E., García-García, J., Sanz, F., & Furlong, L. I. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkw943 · Cited by 2,680 · see citing works
The new NHGRI-EBI Catalog of published genome-wide association studies (GWAS Catalog)
MacArthur, J., Bowler, E., Cerezo, M., Gil, L., Hall, P., Hastings, E., Junkins, H., McMahon, A., Milano, A., Morales, J., et al. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkw1133 · Cited by 2,161 · see citing works
Franz, M., Rodriguez, H., Lopes, C., Zuberi, K., Montojo, J., Bader, G. D., & Morris, Q. (2018) · Nucleic Acids Research · doi:10.1093/nar/gky311 · Cited by 1,413 · see citing works
Walking the Interactome for Prioritization of Candidate Disease Genes
Köhler, S., Bauer, S., Horn, D., & Robinson, P. N. (2008) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2008.02.013 · Cited by 1,268 · see citing works
The Reactome pathway Knowledgebase
Fabregat, A., Sidiropoulos, K., Garapati, P., Gillespie, M., Hausmann, K., Haw, R., Jassal, B., Jupe, S., Korninger, F., McKay, S., et al. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkv1351 · Cited by 1,201 · see citing works
Understanding multicellular function and disease with human tissue-specific networks
Greene, C. S., Krishnan, A., Wong, A. K., Ricciotti, E., Zelaya, R. A., Himmelstein, D. S., Zhang, R., Hartmann, B. M., Zaslavsky, E., Sealfon, S. C., et al. (2015) · Nature Genetics · doi:10.1038/ng.3259 · Cited by 832 · see citing works
The Human Phenotype Ontology in 2017
Köhler, S., Vasilevsky, N., Engelstad, M., Foster, E. D., McMurry, J. A., Aymé, S., Baynam, G. S., Bello, S. M., Boerkoel, C. F., Boycott, K. M., et al. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw1039 · Cited by 757 · see citing works
DSigDB: drug signatures database for gene set analysis
Yoo, M., Shin, J., Kim, J., Ryall, K. A., Lee, K., Lee, S., Jeon, M., Kang, J., & Tan, A. C. (2015) · Bioinformatics · doi:10.1093/bioinformatics/btv313 · Cited by 751 · see citing works
Cytoscape.js: a graph theory library for visualisation and analysis
Franz, M., Lopes, C. T., Huck, G., Yue, D., Sumer, O., & Bader, G. D. (2015) · Bioinformatics · doi:10.1093/bioinformatics/btv557 · Cited by 685 · see citing works
Prioritizing candidate disease genes by network-based boosting of genome-wide association dataPreprint
Lee, I., Singh-Blom, U. M., Wang, P. I., Shim, J. E., & Marcotte, E. M. (2011) · Genome Research · doi:10.1101/gr.118992.110 · Cited by 673 · see citing works
Self-citationWang, T., Yu, H., Hughes, N. W., Liu, B., Kendirli, A., Klein, K., Chen, W. W., Lander, E. S., & Sabatini, D. M. (2017) · Cell · doi:10.1016/j.cell.2017.01.013 · Cited by 632 · see citing works
Nishimura, D. Y. (2001) · Biotech Software & Internet Report · doi:10.1089/152791601750294344 · Cited by 607 · see citing works
Widespread macromolecular interaction perturbations in human genetic disorders
Sahni, N., Yi, S., Taipale, M., Fuxman Bass, J. I., Coulombe-Huntington, J., Yang, F., Peng, J., Weile, J., Karras, G. I., Wang, Y., et al. (2015) · Cell · doi:10.1016/j.cell.2015.04.013 · Cited by 594 · see citing works
DISEASES: Text mining and data integration of disease–gene associations
Pletscher-Frankild, S., Pallejà, A., Tsafou, K., Binder, J. X., & Jensen, L. J. (2015) · Methods · doi:10.1016/j.ymeth.2014.11.020 · Cited by 591 · see citing works
Annotation Transfer Between Genomes: Protein–Protein Interologs and Protein–DNA RegulogsPreprint
Yu, H., Luscombe, N. M., Lu, H. X., Zhu, X., Xia, Y., Han, J. J., Bertin, N., Chung, S., Vidal, M., & Gerstein, M. (2004) · Genome Research · doi:10.1101/gr.1774904 · Cited by 563 · see citing works
Analyzing and interpreting genome data at the network level with ConsensusPathDB
Herwig, R., Hardt, C., Lienhard, M., & Kamburov, A. (2016) · Nature Protocols · doi:10.1038/nprot.2016.117 · Cited by 404 · see citing works
Prolinks: a database of protein functional linkages derived from coevolution
Bowers, P. M., Pellegrini, M. A., Thompson, M. J., Fierro, J., Yeates, T. O., & Eisenberg, D. S. (2004) · Genome biology · doi:10.1186/gb-2004-5-5-r35 · Cited by 303 · see citing works
Systematic Evaluation of Molecular Networks for Discovery of Disease Genes
Huang, J. K., Carlin, D. E., Yu, M. K., Zhang, W., Kreisberg, J. F., Tamayo, P., & Ideker, T. (2018) · Cell Systems · doi:10.1016/j.cels.2018.03.001 · Cited by 289 · see citing works
Korbel, J., Jensen, L., von Mering, C., & Bork, P. (2004) · Nature Biotechnology · doi:10.1038/nbt988 · Cited by 210 · see citing works
Lee, I., Li, Z., & Marcotte, E. M. (2007) · PLoS ONE · doi:10.1371/journal.pone.0000988 · Cited by 183 · see citing works
Self-citationMUFFINN: cancer gene discovery via network analysis of somatic mutation data
Cho, A., Shim, J. E., Kim, E., Supek, F., Lehner, B., & Lee, I. (2016) · Genome biology · doi:10.1186/s13059-016-0989-x · Cited by 160 · see citing works
Self-citationIt's the machine that matters: Predicting gene function and phenotype from protein networks
Wang, P. I., & Marcotte, E. M. (2010) · Journal of Proteomics · doi:10.1016/j.jprot.2010.07.005 · Cited by 117 · see citing works
Self-citationYang, S., Kim, C. Y., Hwang, S., Kim, E., Kim, H., Shim, H., & Lee, I. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw868 · Cited by 105 · see citing works
Self-citationNetSig: network-based discovery from cancer genomes
Horn, H., Lawrence, M. S., Chouinard, C. R., Shrestha, Y., Hu, J. X., Worstell, E., Shea, E., Ilic, N., Kim, E., Kamburov, A., et al. (2018) · Nature Methods · doi:10.1038/nmeth.4514 · Cited by 105 · see citing works
Self-citationPICKLES: the database of pooled in-vitro CRISPR knockout library essentiality screens
Lenoir, W. F., Lim, T. L., & Hart, T. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkx993 · Cited by 94 · see citing works
Self-citationAn unbiased evaluation of gene prioritization tools
Börnigen, D., Tranchevent, L.-C., Capdevila, F. B., Devriendt, K., Moor, B. D., Causmaecker, P. D., & Moreau, Y. (2012) · Bioinformatics · doi:10.1093/bioinformatics/bts581 · Cited by 81 · see citing works
Network Analysis of Differential Expression for the Identification of Disease-Causing Genes
Nitsch, D., Tranchevent, L.-C., Thienpont, B., et al. (2009) · PLoS ONE · doi:10.1371/journal.pone.0005526 · Cited by 71 · see citing works
Network analysis of gene essentiality in functional genomics experiments
Jiang, P., Wang, H., Li, W., Zang, C., Li, B., Wong, Y. J., Meyer, C. A., Liu, J. S., Aster, J. C., & Liu, X. S. (2015) · Genome biology · doi:10.1186/s13059-015-0808-9 · Cited by 59 · see citing works
A large-scale benchmark of gene prioritization methods
Guala, D., & Sonnhammer, E. L. L. (2017) · Scientific Reports · doi:10.1038/srep46598 · Cited by 50 · see citing works
FunCoup 4: new species, data, and visualization
Ogris, C., Guala, D., Kaduk, M., & Sonnhammer, E. L. L. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkx1138 · Cited by 49 · see citing works
MaxLink: network-based prioritization of genes tightly linked to a disease seed set
Guala, D., Sjölund, E., & Sonnhammer, E. L. L. (2014) · Bioinformatics · doi:10.1093/bioinformatics/btu344 · Cited by 33 · see citing works
GWAB: a web server for the network-based boosting of human genome-wide association data
Shim, J. E., Bang, C., Yang, S., et al. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkx284 · Cited by 29 · see citing works
Self-citationFrom sequencing data to gene functions: co-functional network approaches
Shim, J. E., Lee, T. H., & Lee, I. (2017) · Animal Cells and Systems · doi:10.1080/19768354.2017.1284156 · Cited by 28 · see citing works
Self-citationNetwork-based analysis of omics data: the LEAN method
Gwinner, F., Boulday, G., Vandiedonck, C., Arnould, M., Cardoso, C., Nikolayeva, I., Guitart-Pla, O., Denis, C. V., Christophe, O. D., Beghain, J., et al. (2016) · Bioinformatics · doi:10.1093/bioinformatics/btw676 · Cited by 25 · see citing works
Shin, J., & Lee, I. (2015) · PLoS ONE · doi:10.1371/journal.pone.0139006 · Cited by 23 · see citing works
Self-citationShin, J., Lee, T. H., Kim, H., et al. (2013) · Molecular BioSystems · doi:10.1039/c3mb70366e · Cited by 21 · see citing works
Pathway-Dependent Effectiveness of Network Algorithms for Gene Prioritization
Shim, J. E., Hwang, S., & Lee, I. (2015) · PLoS ONE · doi:10.1371/journal.pone.0130589 · Cited by 17 · see citing works
Self-citationWeighted mutual information analysis substantially improves domain-based functional network models
Shim, J. E., & Lee, I. (2016) · Bioinformatics · doi:10.1093/bioinformatics/btw320 · Cited by 15 · see citing works
Self-citationA Framework for Annotating Human Genome in Disease Context
Xu, W. M., Wang, H., Cheng, W., Fu, D., Xia, T., Kibbe, W. A., & Lin, S. M. (2012) · PLoS ONE · doi:10.1371/journal.pone.0049686 · Cited by 11 · see citing works
Construction of Functional Gene Networks Using Phylogenetic Profiles
Shin, J., & Lee, I. (2016) · Methods in molecular biology · doi:10.1007/978-1-4939-6613-4_5 · Cited by 10 · see citing works
Self-citationFunctional gene networks based on the gene neighborhood in metagenomes
Kim, C. Y., & Lee, I. (2017) · Animal Cells and Systems · doi:10.1080/19768354.2017.1382388 · Cited by 8 · see citing works
Self-citation
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Research works printed but not linked: 1
- [23]Nishimura D. BioCarta. Biotech Softw. Int. Rep. 2001; 2: 117– 120.
Cited by
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Szklarczyk, D., Gable, A. L., Nastou, K. C., Lyon, D., Kirsch, R., Pyysalo, S., Doncheva, N. T., Legeay, M., Fang, T., Bork, P., et al. (2021) · Nucleic Acids Research · doi:10.1093/nar/gkaa1074 · Cited by 8,056 · see citing works
Yang, F., Wang, W., Wang, F., Fang, Y., Tang, D., Huang, J., Lu, H., & Yao, J. (2021) · doi:10.1101/2021.12.05.471261 · Cited by 617 · see citing works
Biomedical data, computational methods and tools for evaluating disease–disease associations
Xiang, J., Zhang, J., Zhao, Y., Wu, F.-X., & Li, M. (2022) · Briefings in Bioinformatics · doi:10.1093/bib/bbac006 · Cited by 49 · see citing works
- Authors
- Hwang, S., Kim, C. Y., Yang, S., Kim, E., Hart, T., Marcotte, E. M., & Lee, I.
- Affiliations
- Yonsei University (KR)
- The University of Texas MD Anderson Cancer Center (US)
- The University of Texas at Austin (US)
- Corresponding author
- Lee, Insuk
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2018-11-10
- Volume
- 47
- Issue
- D1
- Pages
- D573-D580
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- PMC
- PMC6323914
- OpenAlex
- W2899728356
- Cited by
- 210
- References
- 48
- Citations by year
- 2026: 5 · 2025: 12 · 2024: 25 · 2023: 31 · 2022: 44 · 2021: 45 · 2020: 31 · 2019: 15 · 2018: 2
- FWCI
- 8.27
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Nucleic Acids Research (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Research Foundation of Korea (NRF-2018M3C9A5064709, NRF-2018R1A5A2025079, NRF-2018R1C1B5032617)
- Welch Foundation (F-1515)
- Cancer Prevention and Research Institute of Texas (RR160032)
- National Institutes of Health (R35GM130119, P30 CA016672)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biomedical Text Mining and Ontologies
- Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
- Keywords
- disease gene prediction, network medicine, gene-disease association, network inference algorithms, multi-omics integration
- MeSH terms
- Algorithms, Disease, Humans, User-Computer Interface, Databases, Genetic, Gene Regulatory Networks
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