{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T00:19:33Z","timestamp":1780877973677,"version":"3.54.1"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2023,6,16]],"date-time":"2023-06-16T00:00:00Z","timestamp":1686873600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001868","name":"National Science Council, Taiwan","doi-asserted-by":"publisher","award":["110-2221-E-001-013-MY3"],"award-info":[{"award-number":["110-2221-E-001-013-MY3"]}],"id":[{"id":"10.13039\/501100001868","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Academia Sinica, Taiwan","award":["AS-GC-110-L15"],"award-info":[{"award-number":["AS-GC-110-L15"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,7,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Protein complexes are key functional units in cellular processes. High-throughput techniques, such as co-fractionation coupled with mass spectrometry (CF-MS), have advanced protein complex studies by enabling global interactome inference. However, dealing with complex fractionation characteristics to define true interactions is not a simple task, since CF-MS is prone to false positives due to the co-elution of non-interacting proteins by chance. Several computational methods have been designed to analyze CF-MS data and construct probabilistic protein\u2013protein interaction (PPI) networks. Current methods usually first infer PPIs based on handcrafted CF-MS features, and then use clustering algorithms to form potential protein complexes. While powerful, these methods suffer from the potential bias of handcrafted features and severely imbalanced data distribution. However, the handcrafted features based on domain knowledge might introduce bias, and current methods also tend to overfit due to the severely imbalanced PPI data. To address these issues, we present a balanced end-to-end learning architecture, Software for Prediction of Interactome with Feature-extraction Free Elution Data (SPIFFED), to integrate feature representation from raw CF-MS data and interactome prediction by convolutional neural network. SPIFFED outperforms the state-of-the-art methods in predicting PPIs under the conventional imbalanced training. When trained with balanced data, SPIFFED had greatly improved sensitivity for true PPIs. Moreover, the ensemble SPIFFED model provides different voting schemes to integrate predicted PPIs from multiple CF-MS data. Using the clustering software (i.e. ClusterONE), SPIFFED allows users to infer high-confidence protein complexes depending on the CF-MS experimental designs. The source code of SPIFFED is freely available at: https:\/\/github.com\/bio-it-station\/SPIFFED.<\/jats:p>","DOI":"10.1093\/bib\/bbad229","type":"journal-article","created":{"date-parts":[[2023,6,17]],"date-time":"2023-06-17T03:06:21Z","timestamp":1686971181000},"source":"Crossref","is-referenced-by-count":4,"title":["A feature extraction free approach for protein interactome inference from co-elution data"],"prefix":"10.1093","volume":"24","author":[{"given":"Yu-Hsin","family":"Chen","sequence":"first","affiliation":[{"name":"National Taiwan University Bioinformatics Program, Taiwan International Graduate Program, , Taipei 106 , Taiwan"},{"name":"Taiwan International Graduate Program, Academic Sinica Bioinformatics Program, , Taipei 11529 , Taiwan"},{"name":"Academia Sinica Institute of Information Science, , Taipei, 11529 , Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuan-Hao","family":"Chao","sequence":"additional","affiliation":[{"name":"Academia Sinica Institute of Information Science, , Taipei, 11529 , Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8705-0283","authenticated-orcid":false,"given":"Jin Yung","family":"Wong","sequence":"additional","affiliation":[{"name":"Academia Sinica Institute of Information Science, , Taipei, 11529 , Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chien-Fu","family":"Liu","sequence":"additional","affiliation":[{"name":"Academia Sinica Institute of Molecular Biology, , Taipei, 11529 , Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun-Yi","family":"Leu","sequence":"additional","affiliation":[{"name":"Academia Sinica Institute of Molecular Biology, , Taipei, 11529 , Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4200-8137","authenticated-orcid":false,"given":"Huai-Kuang","family":"Tsai","sequence":"additional","affiliation":[{"name":"National Taiwan University Bioinformatics Program, Taiwan International Graduate Program, , Taipei 106 , Taiwan"},{"name":"Taiwan International Graduate Program, Academic Sinica Bioinformatics Program, , Taipei 11529 , Taiwan"},{"name":"Academia Sinica Institute of Information Science, , Taipei, 11529 , Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,6,16]]},"reference":[{"key":"2023072020144873100_ref1","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/nrm3970","article-title":"Multidimensional proteomics for cell biology","volume":"16","author":"Larance","year":"2015","journal-title":"Nat Rev Mol Cell Biol"},{"key":"2023072020144873100_ref2","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1038\/nature22366","article-title":"Architecture of the human interactome defines protein communities and disease networks","volume":"545","author":"Huttlin","year":"2017","journal-title":"Nature"},{"key":"2023072020144873100_ref3","doi-asserted-by":"crossref","first-page":"D529","DOI":"10.1093\/nar\/gky1079","article-title":"The BioGRID interaction database: 2019 update","volume":"47","author":"Oughtred","year":"2019","journal-title":"Nucleic Acids Res"},{"key":"2023072020144873100_ref4","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.cbpa.2018.11.003","article-title":"Dynamics of protein complex components","volume":"48","author":"Rattray","year":"2019","journal-title":"Curr Opin Chem Biol"},{"key":"2023072020144873100_ref5","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1002\/mas.21574","article-title":"Discovering cellular protein-protein interactions: technological strategies and opportunities","volume":"38","author":"Titeca","year":"2019","journal-title":"Mass Spectrom Rev"},{"key":"2023072020144873100_ref6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1074\/mcp.R119.001803","article-title":"Next-generation Interactomics: considerations for the use of co-elution to measure protein interaction networks","volume":"19","author":"Salas","year":"2020","journal-title":"Mol Cell Proteomics"},{"key":"2023072020144873100_ref7","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1126\/science.aaw6718","article-title":"Protein interaction networks revealed by proteome coevolution","volume":"365","author":"Cong","year":"2019","journal-title":"Science"},{"key":"2023072020144873100_ref8","doi-asserted-by":"crossref","DOI":"10.1002\/cpps.70","article-title":"Yeast two-hybrid assay to identify interacting proteins","volume":"95","author":"Paiano","year":"2019","journal-title":"Curr Protoc Protein Sci"},{"key":"2023072020144873100_ref9","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1038\/s41586-020-2188-x","article-title":"A reference map of the human binary protein interactome","volume":"580","author":"Luck","year":"2020","journal-title":"Nature"},{"key":"2023072020144873100_ref10","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/j.cell.2015.06.043","article-title":"The BioPlex network: a systematic exploration of the human Interactome","volume":"162","author":"Huttlin","year":"2015","journal-title":"Cell"},{"key":"2023072020144873100_ref11","doi-asserted-by":"crossref","first-page":"3022","DOI":"10.1016\/j.cell.2021.04.011","article-title":"Dual proteome-scale networks reveal cell-specific remodeling of the human interactome","volume":"184","author":"Huttlin","year":"2021","journal-title":"Cell"},{"key":"2023072020144873100_ref12","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1111\/nph.15690","article-title":"Protein and metabolite composition of Arabidopsis stress granules","volume":"222","author":"Kosmacz","year":"2019","journal-title":"New Phytol"},{"key":"2023072020144873100_ref13","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.cell.2006.03.022","article-title":"A mammalian organelle map by protein correlation profiling","volume":"125","author":"Foster","year":"2006","journal-title":"Cell"},{"key":"2023072020144873100_ref14","doi-asserted-by":"crossref","first-page":"1588","DOI":"10.1074\/mcp.RA119.001400","article-title":"A label-free mass spectrometry method to predict endogenous protein complex composition","volume":"18","author":"McBride","year":"2019","journal-title":"Mol Cell Proteomics"},{"key":"2023072020144873100_ref15","doi-asserted-by":"crossref","first-page":"1384","DOI":"10.1093\/molbev\/msaa298","article-title":"Frequent assembly of chimeric complexes in the protein interaction network of an interspecies yeast hybrid","volume":"38","author":"Dandage","year":"2021","journal-title":"Mol Biol Evol"},{"key":"2023072020144873100_ref16","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1016\/j.cell.2012.08.011","article-title":"A census of human soluble protein complexes","volume":"150","author":"Havugimana","year":"2012","journal-title":"Cell"},{"key":"2023072020144873100_ref17","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1038\/nmeth.2131","article-title":"A high-throughput approach for measuring temporal changes in the interactome","volume":"9","author":"Kristensen","year":"2012","journal-title":"Nat Methods"},{"key":"2023072020144873100_ref18","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1038\/nature14877","article-title":"Panorama of ancient metazoan macromolecular complexes","volume":"525","author":"Wan","year":"2015","journal-title":"Nature"},{"key":"2023072020144873100_ref19","doi-asserted-by":"crossref","first-page":"932","DOI":"10.15252\/msb.20167490","article-title":"Integration of over 9,000 mass spectrometry experiments builds a global map of human protein complexes","volume":"13","author":"Drew","year":"2017","journal-title":"Mol Syst Biol"},{"key":"2023072020144873100_ref20","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1186\/s12859-017-1865-8","article-title":"A rapid and accurate approach for prediction of interactomes from co-elution data (PrInCE)","volume":"18","author":"Stacey","year":"2017","journal-title":"BMC Bioinformatics"},{"key":"2023072020144873100_ref21","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1038\/s41592-019-0461-4","article-title":"EPIC: software toolkit for elution profile-based inference of protein complexes","volume":"16","author":"Hu","year":"2019","journal-title":"Nat Methods"},{"key":"2023072020144873100_ref22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1471-2105-11-S11-S1","article-title":"Predicting protein-protein interactions in unbalanced data using the primary structure of proteins","volume":"11","author":"Yu","year":"2010","journal-title":"BMC Bioinform"},{"key":"2023072020144873100_ref23","first-page":"17","article-title":"Limits of end-to-end learning","volume":"77","author":"Glasmachers","year":"2017","journal-title":"J Mach Learn Res"},{"key":"2023072020144873100_ref24","author":"Miech"},{"key":"2023072020144873100_ref25","doi-asserted-by":"crossref","first-page":"1798","DOI":"10.1109\/TPAMI.2013.50","article-title":"Representation learning: a review and new perspectives","volume":"35","author":"Bengio","year":"2012","journal-title":"IEEE Trans Pattern Anal Mach Intell"},{"key":"2023072020144873100_ref26","author":"Yu"},{"key":"2023072020144873100_ref27","author":"Dara"},{"key":"2023072020144873100_ref28","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.talanta.2019.05.053","article-title":"Using deep learning to evaluate peaks in chromatographic data","volume":"204","author":"Risum","year":"2019","journal-title":"Talanta"},{"key":"2023072020144873100_ref29","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1021\/acs.analchem.9b04811","article-title":"Deep learning for the precise peak detection in high-resolution LC-MS data","volume":"92","author":"Melnikov","year":"2020","journal-title":"Anal Chem"},{"key":"2023072020144873100_ref30","doi-asserted-by":"crossref","first-page":"i305","DOI":"10.1093\/bioinformatics\/btz328","article-title":"Multifaceted protein\u2013protein interaction prediction based on Siamese residual RCNN","volume":"35","author":"Chen","year":"2019","journal-title":"Bioinformatics"},{"key":"2023072020144873100_ref31","first-page":"1","article-title":"Predicting protein-protein interactions from matrix-based protein sequence using convolution neural network and feature-selective rotation Forest","volume":"9","author":"Wang","year":"2019","journal-title":"Sci Rep"},{"key":"2023072020144873100_ref32","doi-asserted-by":"crossref","first-page":"2899","DOI":"10.1093\/bioinformatics\/bty1050","article-title":"A simple convolutional neural network for prediction of enhancer-promoter interactions with DNA sequence data","volume":"35","author":"Zhuang","year":"2019","journal-title":"Bioinformatics"},{"key":"2023072020144873100_ref33","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1109\/TCBB.2019.2953908","article-title":"Imbalance data processing strategy for protein interaction sites prediction","volume":"18","author":"Wang","year":"2021","journal-title":"IEEE\/ACM Trans Comput Biol Bioinform"},{"key":"2023072020144873100_ref34","doi-asserted-by":"crossref","first-page":"4180","DOI":"10.1021\/acs.jcim.9b01162","article-title":"Deep learning-based imbalanced data classification for drug discovery","volume":"60","author":"Korkmaz","year":"2020","journal-title":"J Chem Inf Model"},{"key":"2023072020144873100_ref35","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1038\/s41592-021-01194-4","article-title":"Meta-analysis defines principles for the design and analysis of co-fractionation mass spectrometry experiments","volume":"18","author":"Skinnider","year":"2021","journal-title":"Nat Methods"},{"issue":"10","key":"2023072020144873100_ref36","doi-asserted-by":"crossref","first-page":"e1006474","DOI":"10.1371\/journal.pcbi.1006474","article-title":"Genomic data integration systematically biases interactome mapping","volume":"14","author":"Skinnider","year":"2018","journal-title":"PLoS Comput Biol"},{"key":"2023072020144873100_ref37","doi-asserted-by":"crossref","first-page":"4394","DOI":"10.1038\/s41467-022-32107-4","article-title":"Proteotoxicity caused by perturbed protein complexes underlies hybrid incompatibility in yeast","volume":"13","author":"Swamy","year":"2022","journal-title":"Nat Commun"},{"key":"2023072020144873100_ref38","doi-asserted-by":"crossref","first-page":"D543","DOI":"10.1093\/nar\/gkab1038","article-title":"The PRIDE database resources in 2022: a hub for mass spectrometry-based proteomics evidences","volume":"50","author":"Perez-Riverol","year":"2022","journal-title":"Nucleic Acids Res"},{"key":"2023072020144873100_ref39","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1038\/nmeth.1938","article-title":"Detecting overlapping protein complexes in protein-protein interaction networks","volume":"9","author":"Nepusz","year":"2012","journal-title":"Nat Methods"}],"container-title":["Briefings in Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bib\/article-pdf\/24\/4\/bbad229\/50916846\/bbad229.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bib\/article-pdf\/24\/4\/bbad229\/50916846\/bbad229.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,20]],"date-time":"2023-07-20T20:16:45Z","timestamp":1689884205000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bib\/article\/doi\/10.1093\/bib\/bbad229\/7199559"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,16]]},"references-count":39,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2023,7,20]]}},"URL":"https:\/\/doi.org\/10.1093\/bib\/bbad229","relation":{},"ISSN":["1467-5463","1477-4054"],"issn-type":[{"value":"1467-5463","type":"print"},{"value":"1477-4054","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,7]]},"published":{"date-parts":[[2023,6,16]]},"article-number":"bbad229"}}