{"doi":"10.1016/j.ygeno.2024.110963","title":"A fundamental and theoretical framework for mutation interactions and epistasis","abstract":"Many pathological conditions are a result of intragenic epistasis; however, there are ambiguities in current epistasis models. Herein, the new Mutation Interaction Spectrum model defines a discrete outcome, named a Mutation Interaction , for each double point mutation in a gene and its component single mutations. The model is a universal genetic model of all types of mutation interactions and their functional outcomes and is derived from digital logic, commonly used in electrical engineering. Mutation interactions are normally classified as positive and negative epistasis. The model logics unifies common genetic relationships into one model, normalizing biological nomenclature, and disambiguates them with the 16 possible logic-based interactions. The model was tested by assaying transcriptional activity induced by HIV-1 Tat protein, for a random sampling of 3429 double mutations and all 1615 single mutations. All possible types of logic were observed for the Tat mutation interactions. • Universal Genetic Model: The Mutation Interaction Spectrum (MIS) is based on digital logic that precisely classifies mutant interactions and epistasis. • Model Advantages: The MIS unifies and normalizes a literature nomenclature and is extensible to other two component biological systems. • Model Applications: The MIS model disambiguates all possible logics, revealing conservation of logics and -a likely role in selection.","journal":"Genomics","year":2024,"id":482265,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.934,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":826314,"name":"Ronald Benjamin","orcid":"0000-0003-2622-9359","position":1,"is_corresponding":false},{"id":11276,"name":"Jerome I. Rotter","orcid":"0000-0001-7191-1723","position":2,"is_corresponding":false},{"id":516369,"name":"Martin R. Schiller","orcid":"0000-0003-1671-6823","position":3,"is_corresponding":false},{"id":1121136,"name":"Christopher J. Giacoletto","orcid":null,"position":0,"is_corresponding":true}],"reference_count":43,"raw_metadata":null,"created_at":"2026-07-19T02:07:14.349221Z","pmid":"39561884","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}