Iterative random forests to discover predictive and stable high-order interactions
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Abstract
Significance: We developed a predictive, stable, and interpretable tool: the iterative random forest algorithm (iRF). iRF discovers high-order interactions among biomolecules with the same order of computational cost as random forests. We demonstrate the efficacy of iRF by finding known and promising interactions among biomolecules, of up to fifth and sixth order, in two data examples in transcriptional regulation and alternative splicing.
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Stability is a must-have when drawing interpretations from a certain model.
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From Explainable Artificial Intelligence (XAI): Concepts, taxonomies, opportunities and challenges toward responsible AI (2020) · cites this paper as [166]
Trustworthy interpretations should not be produced by models that are not stable.
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From Explainable Artificial Intelligence (XAI): Concepts, taxonomies, opportunities and challenges toward responsible AI (2020) · cites this paper as [166]
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Self-citation
- Authors
- Basu, S., Kumbier, K., Brown, J. B., & Yu, B.
- Affiliations
- Cornell University (US)
- University of California, Berkeley (US)
- Lawrence Berkeley National Laboratory (US)
- Corresponding author
- Brown, James B.
- Yu, Bin
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2018-01-19
- Volume
- 115
- Issue
- 8
- Pages
- 1943-1948
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC5828575
- OpenAlex
- W2731142262
- Cited by
- 317
- References
- 80
- Citations by year
- 2026: 24 · 2025: 32 · 2024: 39 · 2023: 51 · 2022: 48 · 2021: 42 · 2020: 46 · 2019: 20 · 2018: 12 · 2017: 3
- FWCI
- 10.76
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion, cc-by-nc-nd)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- arXiv (Cornell University) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
- arXiv (Cornell University)
- Funders
- HHS | NIH | National Human Genome Research Institute (U01HG007031, R00 HG006698)
- DOD | United States Army | RDECOM | Army Research Office (W911NF1710005)
- DOD | United States Navy | Office of Naval Research (N00014-16-1- 2664)
- U.S. Department of Energy (DOE DE-AC02-05CH11231, DE-SC0017069)
- National Science Foundation (CCF-0939370)
- HHS | NIH |U.S. National Library of Medicine (T32LM012417)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Keywords
- higher-order interactions, epistasis, H3K36me3, epigenetic interactions
- MeSH terms
- Algorithms, Animals, Drosophila, Models, Genetic, Alternative Splicing, Gene Expression Regulation, Developmental, Computational Biology, Gene Regulatory Networks, Genome-Wide Association Study
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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