Show/Hide Menu
Hide/Show Apps
Logout
Türkçe
Türkçe
Search
Search
Login
Login
OpenMETU
OpenMETU
About
About
Open Science Policy
Open Science Policy
Open Access Guideline
Open Access Guideline
Postgraduate Thesis Guideline
Postgraduate Thesis Guideline
Communities & Collections
Communities & Collections
Help
Help
Frequently Asked Questions
Frequently Asked Questions
Guides
Guides
Thesis submission
Thesis submission
MS without thesis term project submission
MS without thesis term project submission
Publication submission with DOI
Publication submission with DOI
Publication submission
Publication submission
Supporting Information
Supporting Information
General Information
General Information
Copyright, Embargo and License
Copyright, Embargo and License
Contact us
Contact us
Revealing third-order interactions through the integration of machine learning and entropy methods in genomic studies
Download
s13040-024-00355-3.pdf
Date
2024-01-01
Author
İyigün, Cem
Aydın Son, Yeşim
Metadata
Show full item record
This work is licensed under a
Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License
.
Item Usage Stats
83
views
29
downloads
Cite This
BackgroundNon-linear relationships at the genotype level are essential in understanding the genetic interactions of complex disease traits. Genome-wide association Studies (GWAS) have revealed statistical association of the SNPs in many complex diseases. As GWAS results could not thoroughly reveal the genetic background of these disorders, Genome-Wide Interaction Studies have started to gain importance. In recent years, various statistical approaches, such as entropy-based methods, have been suggested for revealing these non-additive interactions between variants. This study presents a novel prioritization workflow integrating two-step Random Forest (RF) modeling and entropy analysis after PLINK filtering. PLINK-RF-RF workflow is followed by an entropy-based 3-way interaction information (3WII) method to capture the hidden patterns resulting from non-linear relationships between genotypes in Late-Onset Alzheimer Disease to discover early and differential diagnosis markers.ResultsThree models from different datasets are developed by integrating PLINK-RF-RF analysis and entropy-based three-way interaction information (3WII) calculation method, which enables the detection of the third-order interactions, which are not primarily considered in epistatic interaction studies. A reduced SNP set is selected for all three datasets by 3WII analysis by PLINK filtering and prioritization of SNP with RF-RF modeling, promising as a model minimization approach. Among SNPs revealed by 3WII, 4 SNPs out of 19 from GenADA, 1 SNP out of 27 from ADNI, and 4 SNPs out of 106 from NCRAD are mapped to genes directly associated with Alzheimer Disease. Additionally, several SNPs are associated with other neurological disorders. Also, the genes the variants mapped to in all datasets are significantly enriched in calcium ion binding, extracellular matrix, external encapsulating structure, and RUNX1 regulates estrogen receptor-mediated transcription pathways. Therefore, these functional pathways are proposed for further examination for a possible LOAD association. Besides, all 3WII variants are proposed as candidate biomarkers for the genotyping-based LOAD diagnosis.ConclusionThe entropy approach performed in this study reveals the complex genetic interactions that significantly contribute to LOAD risk. We benefited from the entropy-based 3WII as a model minimization step and determined the significant 3-way interactions between the prioritized SNPs by PLINK-RF-RF. This framework is a promising approach for disease association studies, which can also be modified by integrating other machine learning and entropy-based interaction methods.
URI
https://biodatamining.biomedcentral.com/articles/10.1186/s13040-024-00355-3
https://hdl.handle.net/11511/108625
Journal
BIODATA MINING
DOI
https://doi.org/10.1186/s13040-024-00355-3
Collections
Department of Industrial Engineering, Article
Citation Formats
IEEE
ACM
APA
CHICAGO
MLA
BibTeX
C. İyigün and Y. Aydın Son, “Revealing third-order interactions through the integration of machine learning and entropy methods in genomic studies,”
BIODATA MINING
, no. 1, pp. 0–0, 2024, Accessed: 00, 2024. [Online]. Available: https://biodatamining.biomedcentral.com/articles/10.1186/s13040-024-00355-3.