{"doi":"10.1101/2024.04.05.588302","title":"TopDIA: A Software Tool for Top-Down Data-Independent Acquisition Proteomics","abstract":"Abstract Top-down mass spectrometry is widely used for proteoform identification, characterization, and quantification owing to its ability to analyze intact proteoforms. In the last decade, top-down proteomics has been dominated by top-down data-dependent acquisition mass spectrometry (TD-DDA-MS), and top-down data-independent acquisition mass spectrometry (TD-DIA-MS) has not been well studied. While TD-DIA-MS produces complex multiplexed tandem mass spectrometry (MS/MS) spectra, which are challenging to confidently identify, it selects more precursor ions for MS/MS analysis and has the potential to increase proteoform identifications compared with TD-DDA-MS. Here we present TopDIA, the first software tool for proteoform identification by TD-DIA-MS. It generates demultiplexed pseudo MS/MS spectra from TD-DIA-MS data and then searches the pseudo MS/MS spectra against a protein sequence database for proteoform identification. We compared the performance of TD-DDA-MS and TD-DIA-MS using Escherichia coli K-12 MG1655 cells and demonstrated that TD-DIA-MS with TopDIA increased proteoform and protein identifications compared with TD-DDA-MS.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":486066,"datarank":0.2872929776276972,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"self_citation_contribution":0.24141568686511508,"citation_network_contribution":0.0458772907625821,"self_endowment_contribution":0.24141568686511508,"citer_contribution":0.0458772907625821,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":2,"citers_with_citation_signal":2,"citers_with_endowment":2,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9595,"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":1281738,"name":"Xingzhao Xiong","orcid":"0000-0002-9384-4573","position":1,"is_corresponding":false},{"id":683356,"name":"Tian Xu","orcid":"0000-0003-1464-6008","position":2,"is_corresponding":false},{"id":454680,"name":"Yong Zang","orcid":"0000-0003-0572-4756","position":3,"is_corresponding":false},{"id":411770,"name":"Liangliang Sun","orcid":"0000-0001-8939-5042","position":4,"is_corresponding":false},{"id":298237,"name":"Xiaowen Liu","orcid":"0000-0003-4139-1127","position":5,"is_corresponding":false},{"id":985677,"name":"Abdul Rehman Basharat","orcid":"0000-0002-4675-5375","position":0,"is_corresponding":true}],"reference_count":52,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:07:57.049469Z","pmid":"38645171","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":[]}