{"doi":"10.1101/gr.279132.124","title":"Parameter-efficient fine-tuning on large protein language models improves signal peptide prediction","abstract":"Signal peptides (SPs) play a crucial role in protein translocation in cells. The development of large protein language models (PLMs) and prompt-based learning provide a new opportunity for SP prediction, especially for the categories with limited annotated data. We present a parameter-efficient fine-tuning (PEFT) framework for SP prediction, PEFT-SP, to effectively utilize pretrained PLMs. We integrated low-rank adaptation (LoRA) into ESM-2 models to better leverage the protein sequence evolutionary knowledge of PLMs. Experiments show that PEFT-SP using LoRA enhances state-of-the-art results, leading to a maximum Matthews correlation coefficient (MCC) gain of 87.3% for SPs with small training samples and an overall MCC gain of 6.1%. Furthermore, we also employed two other PEFT methods, prompt tuning and adapter tuning, in ESM-2 for SP prediction. More elaborate experiments show that PEFT-SP using adapter tuning can also improve the state-of-the-art results by up to 28.1% MCC gain for SPs with small training samples and an overall MCC gain of 3.8%. LoRA requires fewer computing resources and less memory than the adapter tuning during the training stage, making it possible to adapt larger and more powerful protein models for SP prediction.","journal":"Genome Research","year":2024,"id":483934,"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":31,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9536,"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":233619,"name":"Duolin Wang","orcid":"0000-0003-1649-460X","position":1,"is_corresponding":false},{"id":56120,"name":"Lei Jiang","orcid":"0000-0003-4579-728X","position":2,"is_corresponding":false},{"id":233623,"name":"Dong Xu","orcid":"0000-0002-4809-0514","position":3,"is_corresponding":false},{"id":670897,"name":"Shuai Zeng","orcid":"0000-0001-7632-427X","position":0,"is_corresponding":true}],"reference_count":45,"raw_metadata":null,"created_at":"2026-07-19T02:07:38.055693Z","pmid":"39060029","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":[]}