{"paper":{"title":"High-Order Epistasis Detection Using Factorization Machine with Quadratic Optimization Annealing and MDR-Based Evaluation","license":"http://creativecommons.org/licenses/by/4.0/","headline":"Factorization machine quadratic annealing recovers ground-truth high-order epistasis by optimizing MDR error rates as a black-box objective.","cross_cats":["quant-ph"],"primary_cat":"cs.LG","authors_text":"Shuta Kikuchi, Shu Tanaka","submitted_at":"2026-01-05T07:41:34Z","abstract_excerpt":"Detecting high-order epistasis is a fundamental challenge in genetic association studies due to the combinatorial explosion of candidate locus combinations. Although multifactor dimensionality reduction (MDR) is a widely used method for evaluating epistasis, exhaustive MDR-based searches become computationally infeasible as the number of loci or the interaction order increases. In this paper, we define the epistasis detection problem as a black-box optimization problem and solve it with a factorization machine with quadratic-optimization annealing (FMQA). We propose an efficient epistasis dete"},"claims":{"count":4,"items":[{"kind":"strongest_claim","text":"The proposed method successfully identified ground-truth epistasis across various interaction orders and the numbers of genetic loci within a limited number of iterations.","source":"verdict.strongest_claim","status":"machine_extracted","claim_id":"C1","attestation":"unclaimed"},{"kind":"weakest_assumption","text":"That performance on simulated datasets with artificially planted high-order epistasis will translate to real genetic data where interaction patterns are unknown and noise structures differ.","source":"verdict.weakest_assumption","status":"machine_extracted","claim_id":"C2","attestation":"unclaimed"},{"kind":"one_line_summary","text":"FMQA optimizes MDR classification error rates to identify predefined high-order epistatic interactions in simulated genetic datasets within limited iterations.","source":"verdict.one_line_summary","status":"machine_extracted","claim_id":"C3","attestation":"unclaimed"},{"kind":"headline","text":"Factorization machine quadratic annealing recovers ground-truth high-order epistasis by optimizing MDR error rates as a black-box objective.","source":"verdict.pith_extraction.headline","status":"machine_extracted","claim_id":"C4","attestation":"unclaimed"}],"snapshot_sha256":"5451204f1aa672ab29363c36ba6ed52a1332edf108030c258652105d4ce3a6dd"},"source":{"id":"2601.01860","kind":"arxiv","version":2},"verdict":{"id":"65cb1fec-373b-423b-aa03-ab3d3b460f28","model_set":{"reader":"grok-4.3"},"created_at":"2026-05-16T17:33:13.923564Z","strongest_claim":"The proposed method successfully identified ground-truth epistasis across various interaction orders and the numbers of genetic loci within a limited number of iterations.","one_line_summary":"FMQA optimizes MDR classification error rates to identify predefined high-order epistatic interactions in simulated genetic datasets within limited iterations.","pipeline_version":"pith-pipeline@v0.9.0","weakest_assumption":"That performance on simulated datasets with artificially planted high-order epistasis will translate to real genetic data where interaction patterns are unknown and noise structures differ.","pith_extraction_headline":"Factorization machine quadratic annealing recovers ground-truth high-order epistasis by optimizing MDR error rates as a black-box objective."},"references":{"count":29,"sample":[{"doi":"","year":2003,"title":"An introduction to variable and feature selection,","work_id":"4d152cfc-e623-4090-9e4b-f60319ef82e8","ref_index":1,"cited_arxiv_id":"","is_internal_anchor":false},{"doi":"","year":2007,"title":"A review of feature selection techniques in bioinformatics,","work_id":"eef3a70b-47f1-4163-9801-2d1637447484","ref_index":2,"cited_arxiv_id":"","is_internal_anchor":false},{"doi":"","year":2068,"title":"Research techniques made simple: feature selection for biomarker discovery,","work_id":"195a38a5-2767-4e42-8522-6e510eb0803c","ref_index":3,"cited_arxiv_id":"","is_internal_anchor":false},{"doi":"","year":2014,"title":"Genetic interactions involving five or more genes contribute to a complex trait in yeast,","work_id":"b72a7f4c-58c2-4b87-b7c3-0e72deb171dd","ref_index":4,"cited_arxiv_id":"","is_internal_anchor":false},{"doi":"","year":2015,"title":"Higher-order genetic interactions and their contribution to com- plex traits,","work_id":"9175c47a-a8d7-4679-914a-fe6d726a42e0","ref_index":5,"cited_arxiv_id":"","is_internal_anchor":false}],"resolved_work":29,"snapshot_sha256":"61edb1cf5a7a1d42967596bf8e7247e483cc14a41ab2a564a9fa7b990c92ddb0","internal_anchors":1},"formal_canon":{"evidence_count":2,"snapshot_sha256":"3ad9b49067b53ddea7fb6446db5d8b13adc3142b845463815f0561840d9d4be6"},"author_claims":{"count":0,"strong_count":0,"snapshot_sha256":"258153158e38e3291e3d48162225fcdb2d5a3ed65a07baac614ab91432fd4f57"},"builder_version":"pith-number-builder-2026-05-17-v1"}