Yetong Zhou, Shengming Zhou, Yue Bi, Quan Zou, Cangzhi Jia
{"title":"A two-task predictor for discovering phase separation proteins and their undergoing mechanism.","authors":"Yetong Zhou, Shengming Zhou, Yue Bi, Quan Zou, Cangzhi Jia","doi":"10.1093/bib/bbae528","DOIUrl":null,"url":null,"abstract":"<p><p>Liquid-liquid phase separation (LLPS) is one of the mechanisms mediating the compartmentalization of macromolecules (proteins and nucleic acids) in cells, forming biomolecular condensates or membraneless organelles. Consequently, the systematic identification of potential LLPS proteins is crucial for understanding the phase separation process and its biological mechanisms. A two-task predictor, Opt_PredLLPS, was developed to discover potential phase separation proteins and further evaluate their mechanism. The first task model of Opt_PredLLPS combines a convolutional neural network (CNN) and bidirectional long short-term memory (BiLSTM) through a fully connected layer, where the CNN utilizes evolutionary information features as input, and BiLSTM utilizes multimodal features as input. If a protein is predicted to be an LLPS protein, it is input into the second task model to predict whether this protein needs to interact with its partners to undergo LLPS. The second task model employs the XGBoost classification algorithm and 37 physicochemical properties following a three-step feature selection. The effectiveness of the model was validated on multiple benchmark datasets, and in silico saturation mutagenesis was used to identify regions that play a key role in phase separation. These findings may assist future research on the LLPS mechanism and the discovery of potential phase separation proteins.</p>","PeriodicalId":9209,"journal":{"name":"Briefings in bioinformatics","volume":null,"pages":null},"PeriodicalIF":6.8000,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11492799/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Briefings in bioinformatics","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1093/bib/bbae528","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}
引用次数: 0
Abstract
Liquid-liquid phase separation (LLPS) is one of the mechanisms mediating the compartmentalization of macromolecules (proteins and nucleic acids) in cells, forming biomolecular condensates or membraneless organelles. Consequently, the systematic identification of potential LLPS proteins is crucial for understanding the phase separation process and its biological mechanisms. A two-task predictor, Opt_PredLLPS, was developed to discover potential phase separation proteins and further evaluate their mechanism. The first task model of Opt_PredLLPS combines a convolutional neural network (CNN) and bidirectional long short-term memory (BiLSTM) through a fully connected layer, where the CNN utilizes evolutionary information features as input, and BiLSTM utilizes multimodal features as input. If a protein is predicted to be an LLPS protein, it is input into the second task model to predict whether this protein needs to interact with its partners to undergo LLPS. The second task model employs the XGBoost classification algorithm and 37 physicochemical properties following a three-step feature selection. The effectiveness of the model was validated on multiple benchmark datasets, and in silico saturation mutagenesis was used to identify regions that play a key role in phase separation. These findings may assist future research on the LLPS mechanism and the discovery of potential phase separation proteins.
期刊介绍:
Briefings in Bioinformatics is an international journal serving as a platform for researchers and educators in the life sciences. It also appeals to mathematicians, statisticians, and computer scientists applying their expertise to biological challenges. The journal focuses on reviews tailored for users of databases and analytical tools in contemporary genetics, molecular and systems biology. It stands out by offering practical assistance and guidance to non-specialists in computerized methodologies. Covering a wide range from introductory concepts to specific protocols and analyses, the papers address bacterial, plant, fungal, animal, and human data.
The journal's detailed subject areas include genetic studies of phenotypes and genotypes, mapping, DNA sequencing, expression profiling, gene expression studies, microarrays, alignment methods, protein profiles and HMMs, lipids, metabolic and signaling pathways, structure determination and function prediction, phylogenetic studies, and education and training.