Summary: Analyzing biological networks demands scalable annotation tools, yet existing methods fall short in clustering power, statistical flexibility, and broad data compatibility. We introduce Regional Inference of Significant Kinships (RISK), a next-generation tool that overcomes these challenges by integrating community detection algorithms, rigorous overrepresentation analysis, and a modular architecture that supports diverse network types. RISK identifies biologically coherent relationships within networks and generates publication-ready visualizations, as demonstrated by its ability to resolve compact functional modules in Saccharomyces cerevisiae protein-protein interaction and genetic interaction networks. Its application to a high-energy physics citation network reveals structured relationships among research subfields, highlighting its versatility beyond biological systems. As biological and interdisciplinary networks increase in size and complexity, RISK's scalability and adaptability make it a powerful solution for modern network analysis.
Availability and implementation: RISK is compatible with Python 3.8 or later, supports all major operating systems, and can be installed via pip. The software is open source under the GPLv3 license on GitHub (https://github.com/riskportal/risk) and archived on Zenodo (https://doi.org/10.5281/zenodo.17257418). Documentation and a step-by-step Jupyter notebook tutorial are available at https://github.com/riskportal/risk-docs.
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| Evidence ID | Analyze ID | Gene/Complex | Systematic Name/Complex Accession | Qualifier | Gene Ontology Term ID | Gene Ontology Term | Aspect | Annotation Extension | Evidence | Method | Source | Assigned On | Reference |
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| Evidence ID | Analyze ID | Gene | Gene Systematic Name | Phenotype | Experiment Type | Experiment Type Category | Mutant Information | Strain Background | Chemical | Details | Reference |
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| Evidence ID | Analyze ID | Gene | Gene Systematic Name | Disease Ontology Term | Disease Ontology Term ID | Qualifier | Evidence | Method | Source | Assigned On | Reference |
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| Evidence ID | Analyze ID | Regulator | Regulator Systematic Name | Target | Target Systematic Name | Direction | Regulation of | Happens During | Regulator Type | Direction | Regulation Of | Happens During | Method | Evidence | Strain Background | Reference |
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| Site | Modification | Modifier | Source | Reference |
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Increase the total number of rows showing on this page by using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table; click on the small "i" buttons located within a cell for an annotation to view further details about experiment type and any other genes involved in the interaction.
| Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Allele | Assay | Annotation | Action | Phenotype | SGA score | P-value | Source | Reference | Note |
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Increase the total number of rows showing on this page by using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table; click on the small "i" buttons located within a cell for an annotation to view further details about experiment type and any other genes involved in the interaction.
| Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Assay | Annotation | Action | Modification | Source | Reference | Note |
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| Complement ID | Locus ID | Gene | Species | Gene ID | Strain background | Direction | Details | Source | Reference |
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| Evidence ID | Analyze ID | Dataset | Description | Keywords | Number of Conditions | Reference |
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| Evidence ID | Analyze ID | File | Description |
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