{"doi":"10.1016/j.csbj.2025.02.012","title":"MMRT: MultiMut Recursive Tree for predicting functional effects of high-order protein variants from low-order variants","abstract":"(MMRT), to address this challenge of predicting the functional effects of high-order variants. MMRT integrates deep learning with a recursive tree framework to leverage the information from low-order variants to predict functional effects of high-order variants. We evaluated MMRT on datasets comprising 685,593 high-order variants. Our results (mean Spearman's correlation coefficient 0.55) demonstrated that MMRT outperformed three existing state-of-the-art methods: ESM (evolutionary scale modeling), DeepSequence, and ECNet (evolutionary context-integrated neural network). MMRT thus provides more accurate prediction of the functional effects of high-order protein variants, offering great potential for aiding the interpretation of variants in human disease studies.","journal":"Computational and Structural Biotechnology Journal","year":2025,"id":543154,"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":0.9469,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1072546,"name":"Houssemeddine Derbel","orcid":null,"position":1,"is_corresponding":false},{"id":13182,"name":"Zhongming Zhao","orcid":"0000-0002-3477-0914","position":2,"is_corresponding":false},{"id":1072034,"name":"Qian Liu","orcid":"0000-0002-6737-4969","position":3,"is_corresponding":false},{"id":1432871,"name":"Bryce Forrest","orcid":null,"position":0,"is_corresponding":true}],"reference_count":62,"raw_metadata":null,"created_at":"2026-07-19T02:53:00.171379Z","pmid":"40070521","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":[]}