Pub Date : 2024-12-05DOI: 10.1016/j.biotechadv.2024.108497
Wenwen Yu , Ke Jin , Xianhao Xu , Yanfeng Liu , Jianghua Li , Guocheng Du , Jian Chen , Xueqin Lv , Long Liu
Generally, the metabolism in microbial organism is an intricate, spatiotemporal process that emerges from gene regulatory networks, which affects the efficiency of product biosynthesis. With the coming age of synthetic biology, spatiotemporal control systems have been explored as versatile strategies to promote product biosynthesis at both spatial and temporal levels. Meanwhile, the designer synthetic compartments provide new and promising approaches to engineerable spatiotemporal control systems to construct high-performance microbial cell factories. In this article, we comprehensively summarize recent developments in spatiotemporal control systems for tailoring advanced cell factories, and illustrate how to apply spatiotemporal control systems in different microbial species with desired applications. Future challenges of spatiotemporal control systems and perspectives are also discussed.
{"title":"Engineering microbial cell factories by multiplexed spatiotemporal control of cellular metabolism: Advances, challenges, and future perspectives","authors":"Wenwen Yu , Ke Jin , Xianhao Xu , Yanfeng Liu , Jianghua Li , Guocheng Du , Jian Chen , Xueqin Lv , Long Liu","doi":"10.1016/j.biotechadv.2024.108497","DOIUrl":"10.1016/j.biotechadv.2024.108497","url":null,"abstract":"<div><div>Generally, the metabolism in microbial organism is an intricate, spatiotemporal process that emerges from gene regulatory networks, which affects the efficiency of product biosynthesis. With the coming age of synthetic biology, spatiotemporal control systems have been explored as versatile strategies to promote product biosynthesis at both spatial and temporal levels. Meanwhile, the designer synthetic compartments provide new and promising approaches to engineerable spatiotemporal control systems to construct high-performance microbial cell factories. In this article, we comprehensively summarize recent developments in spatiotemporal control systems for tailoring advanced cell factories, and illustrate how to apply spatiotemporal control systems in different microbial species with desired applications. Future challenges of spatiotemporal control systems and perspectives are also discussed.</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"79 ","pages":"Article 108497"},"PeriodicalIF":12.1,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-05DOI: 10.1016/j.biotechadv.2024.108495
David Medina-Ortiz , Ashkan Khalifeh , Hoda Anvari-Kazemabad , Mehdi D. Davari
Protein engineering through directed evolution and (semi)rational design has become a powerful approach for optimizing and enhancing proteins with desired properties. The integration of artificial intelligence methods has further accelerated protein engineering process by enabling the development of predictive models based on data-driven strategies. However, the lack of interpretability and transparency in these models limits their trustworthiness and applicability in real-world scenarios. Explainable Artificial Intelligence addresses these challenges by providing insights into the decision-making processes of machine learning models, enhancing their reliability and interpretability. Explainable strategies has been successfully applied in various biotechnology fields, including drug discovery, genomics, and medicine, yet its application in protein engineering remains underexplored. The incorporation of explainable strategies in protein engineering holds significant potential, as it can guide protein design by revealing how predictive models function, benefiting approaches such as machine learning-assisted directed evolution. This perspective work explores the principles and methodologies of explainable artificial intelligence, highlighting its relevance in biotechnology and its potential to enhance protein design. Additionally, three theoretical pipelines integrating predictive models with explainable strategies are proposed, focusing on their advantages, disadvantages, and technical requirements. Finally, the remaining challenges of explainable artificial intelligence in protein engineering and future directions for its development as a support tool for traditional protein engineering methodologies are discussed.
{"title":"Interpretable and explainable predictive machine learning models for data-driven protein engineering","authors":"David Medina-Ortiz , Ashkan Khalifeh , Hoda Anvari-Kazemabad , Mehdi D. Davari","doi":"10.1016/j.biotechadv.2024.108495","DOIUrl":"10.1016/j.biotechadv.2024.108495","url":null,"abstract":"<div><div>Protein engineering through directed evolution and (semi)rational design has become a powerful approach for optimizing and enhancing proteins with desired properties. The integration of artificial intelligence methods has further accelerated protein engineering process by enabling the development of predictive models based on data-driven strategies. However, the lack of interpretability and transparency in these models limits their trustworthiness and applicability in real-world scenarios. Explainable Artificial Intelligence addresses these challenges by providing insights into the decision-making processes of machine learning models, enhancing their reliability and interpretability. Explainable strategies has been successfully applied in various biotechnology fields, including drug discovery, genomics, and medicine, yet its application in protein engineering remains underexplored. The incorporation of explainable strategies in protein engineering holds significant potential, as it can guide protein design by revealing how predictive models function, benefiting approaches such as machine learning-assisted directed evolution. This perspective work explores the principles and methodologies of explainable artificial intelligence, highlighting its relevance in biotechnology and its potential to enhance protein design. Additionally, three theoretical pipelines integrating predictive models with explainable strategies are proposed, focusing on their advantages, disadvantages, and technical requirements. Finally, the remaining challenges of explainable artificial intelligence in protein engineering and future directions for its development as a support tool for traditional protein engineering methodologies are discussed.</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"79 ","pages":"Article 108495"},"PeriodicalIF":12.1,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-03DOI: 10.1016/j.biotechadv.2024.108492
Saber Imani , Shuojie Lv , Hongbo Qian , Yulan Cui , XiaoYan Li , Ali Babaeizad , Qingjing Wang
The prevalence of multidrug-resistant (MDR) ESKAPE pathogens, including Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa, represents a critical global public health challenge. In response, mRNA vaccines offer an adaptable and scalable platform for immunotherapy against ESKAPE pathogens by encoding specific antigens that stimulate B-cell-driven antibody production and CD8+ T-cell-mediated cytotoxicity, effectively neutralizing these pathogens and combating resistance. This review examines recent advancements and ongoing challenges in the development of mRNA vaccines targeting MDR ESKAPE pathogens. We explore antigen selection, the nuances of mRNA vaccine technology, and the complex interactions between bacterial infections and antibiotic resistance. By assessing the potential efficacy of mRNA vaccines and addressing key barriers to their paraclinical implementation, this review highlights the promising function of mRNA-based immunization in combating MDR ESKAPE pathogens.
{"title":"Current innovations in mRNA vaccines for targeting multidrug-resistant ESKAPE pathogens","authors":"Saber Imani , Shuojie Lv , Hongbo Qian , Yulan Cui , XiaoYan Li , Ali Babaeizad , Qingjing Wang","doi":"10.1016/j.biotechadv.2024.108492","DOIUrl":"10.1016/j.biotechadv.2024.108492","url":null,"abstract":"<div><div>The prevalence of multidrug-resistant (MDR) ESKAPE pathogens, including <em>Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa</em>, represents a critical global public health challenge. In response, mRNA vaccines offer an adaptable and scalable platform for immunotherapy against ESKAPE pathogens by encoding specific antigens that stimulate B-cell-driven antibody production and CD8<sup>+</sup> T-cell-mediated cytotoxicity, effectively neutralizing these pathogens and combating resistance. This review examines recent advancements and ongoing challenges in the development of mRNA vaccines targeting MDR ESKAPE pathogens. We explore antigen selection, the nuances of mRNA vaccine technology, and the complex interactions between bacterial infections and antibiotic resistance. By assessing the potential efficacy of mRNA vaccines and addressing key barriers to their paraclinical implementation, this review highlights the promising function of mRNA-based immunization in combating MDR ESKAPE pathogens.</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"79 ","pages":"Article 108492"},"PeriodicalIF":12.1,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142784050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-26DOI: 10.1016/j.biotechadv.2024.108491
Yangyang Hu , Guangyu Jiang , Yalun Wen , Yuchen Shao , Ge Yang , Feng Qu
Aptamers, as novel recognition molecules, hold immense potential across various domains such as biosensing, nucleic acid drugs, medical diagnostics, as well as environmental and food analysis. The majority of aptamer selection processes targeting small molecules and protein commonly employ magnetic bead-based methodologies, wherein the target is initially immobilized on magnetic beads, followed by magnetic separation. The Evolutionary Systematic Evolution of Ligands by Exponential Enrichment technique based on capillary electrophoresis (CE-SELEX) is acknowledged as one of the most efficient screening methods. Our research group has achieved breakthroughs in employing CE-SELEX for the selection of aptamers targeting small molecules. This paper outlines specific methodologies utilized from 2005 to 2023 for CE-SELEX screening for small-molecule targets. It summarizes the methods for the separation of small molecules and oligonucleotide complexes, as well as the identification of candidate aptamers. Drawing upon our research group's extensive experience in CE-SELEX for selecting aptamers targeting multi-scale targets, we offer strategic guidance specifically tailored to the screening of aptamers for small-molecule targets using CE-SELEX. This includes systematic insights into each technical aspect of the screening process: analysis of the structure of small-molecule targets and characteristics of ssDNA libraries, patterns of CE separation and collection of complexes, screening strategies, and CE-based methods for the affinity and specificity characterization of aptamers. This comprehensive review aims to contribute to the widespread adoption of CE-SELEX technology, enhancing the efficiency and success rate of selecting aptamers for small-molecule targets.
{"title":"Selection of aptamers targeting small molecules by capillary electrophoresis: Advances, challenges, and prospects","authors":"Yangyang Hu , Guangyu Jiang , Yalun Wen , Yuchen Shao , Ge Yang , Feng Qu","doi":"10.1016/j.biotechadv.2024.108491","DOIUrl":"10.1016/j.biotechadv.2024.108491","url":null,"abstract":"<div><div>Aptamers, as novel recognition molecules, hold immense potential across various domains such as biosensing, nucleic acid drugs, medical diagnostics, as well as environmental and food analysis. The majority of aptamer selection processes targeting small molecules and protein commonly employ magnetic bead-based methodologies, wherein the target is initially immobilized on magnetic beads, followed by magnetic separation. The Evolutionary Systematic Evolution of Ligands by Exponential Enrichment technique based on capillary electrophoresis (CE-SELEX) is acknowledged as one of the most efficient screening methods. Our research group has achieved breakthroughs in employing CE-SELEX for the selection of aptamers targeting small molecules. This paper outlines specific methodologies utilized from 2005 to 2023 for CE-SELEX screening for small-molecule targets. It summarizes the methods for the separation of small molecules and oligonucleotide complexes, as well as the identification of candidate aptamers. Drawing upon our research group's extensive experience in CE-SELEX for selecting aptamers targeting multi-scale targets, we offer strategic guidance specifically tailored to the screening of aptamers for small-molecule targets using CE-SELEX. This includes systematic insights into each technical aspect of the screening process: analysis of the structure of small-molecule targets and characteristics of ssDNA libraries, patterns of CE separation and collection of complexes, screening strategies, and CE-based methods for the affinity and specificity characterization of aptamers. This comprehensive review aims to contribute to the widespread adoption of CE-SELEX technology, enhancing the efficiency and success rate of selecting aptamers for small-molecule targets.</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"78 ","pages":"Article 108491"},"PeriodicalIF":12.1,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142738184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-22DOI: 10.1016/j.biotechadv.2024.108481
Cheng Chen , Ya-Wen Li , Yuan-Yuan Zheng , Xiu-Juan Li , Na Wu , Qi Guo , Tian-Qiong Shi , He Huang
Genome engineering is extensively utilized in diverse scientific disciplines, advancing human welfare and addressing various challenges. Numerous genome engineering tools have been developed to modify genomic sequences. Among these, the CRISPR-Cas system has transformed the field and remains the most commonly employed genome-editing tool. However, the CRISPR-Cas system relies on induced double-strand breaks, with editing efficiency often limited by factors such as cell type and homologous recombination, impeding further progress. CRISPR-associated transposons (CASTs) represent programmable mobile genetic elements. CASTs identified as active were developed as CAST systems, which can perform RNA-guided DNA integration and are featured by high precision, programmability, and kilobase-level payload capacity. Moreover, CAST system allows for precise genome modifications independent of host DNA repair mechanisms, addressing the constraints of conventional CRISPR-Cas systems. It expands the genome engineering toolkit and is poised to become a representative of next-generation genome editing tools. This review thoroughly examines the research progress on CASTs, highlighting the current challenges faced in genome engineering based on CASTs, and offering insights into the ongoing development of this transformative technology.
{"title":"Expanding the frontiers of genome engineering: A comprehensive review of CRISPR-associated transposons","authors":"Cheng Chen , Ya-Wen Li , Yuan-Yuan Zheng , Xiu-Juan Li , Na Wu , Qi Guo , Tian-Qiong Shi , He Huang","doi":"10.1016/j.biotechadv.2024.108481","DOIUrl":"10.1016/j.biotechadv.2024.108481","url":null,"abstract":"<div><div>Genome engineering is extensively utilized in diverse scientific disciplines, advancing human welfare and addressing various challenges. Numerous genome engineering tools have been developed to modify genomic sequences. Among these, the CRISPR-Cas system has transformed the field and remains the most commonly employed genome-editing tool. However, the CRISPR-Cas system relies on induced double-strand breaks, with editing efficiency often limited by factors such as cell type and homologous recombination, impeding further progress. CRISPR-associated transposons (CASTs) represent programmable mobile genetic elements. CASTs identified as active were developed as CAST systems, which can perform RNA-guided DNA integration and are featured by high precision, programmability, and kilobase-level payload capacity. Moreover, CAST system allows for precise genome modifications independent of host DNA repair mechanisms, addressing the constraints of conventional CRISPR-Cas systems. It expands the genome engineering toolkit and is poised to become a representative of next-generation genome editing tools. This review thoroughly examines the research progress on CASTs, highlighting the current challenges faced in genome engineering based on CASTs, and offering insights into the ongoing development of this transformative technology.</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"78 ","pages":"Article 108481"},"PeriodicalIF":12.1,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-21DOI: 10.1016/j.biotechadv.2024.108482
Xiaoting Yu , Huiling Zhang , Tao Zhou , Kangliang Pan , Sayed Haidar Abbas Raza , Xing Shen , Hongtao Lei
Historically, antibodies have been divided into two functionally independent domains, the variable (V) region for antigen binding and the constant (C) region for mediating effector functions. However, this classical view of antibody function has been severely challenged by a large and growing number of studies, which reveal long-range conformational interactions and allosteric links between the V and C regions. This review comprehensively summarizes the existing studies on antibody allostery, including allosteric conformational changes induced by covalent modifications or noncovalent ligand binding. In addition, we discuss how intramolecular allosteric signals are transmitted from the V to C regions and vice versa. This review argues that there is sufficient evidence to revisit the structure-function relationship of antibodies. These advances in antibody allostery will provide a blueprint for regulating antibody functions in a simple and highly predictable manner. More focus on antibody allostery will definitely benefit antibody engineering and vaccine design in the field of biotechnology.
一直以来，抗体被划分为两个功能独立的结构域，可变区（V）用于抗原结合，恒定区（C）用于介导效应功能。然而，大量且日益增多的研究揭示了 V 区和 C 区之间的长程构象相互作用和异构联系，这对抗体功能的经典观点提出了严峻挑战。本综述全面总结了现有的抗体异构研究，包括共价修饰或非共价配体结合诱导的异构构象变化。此外，我们还讨论了分子内异构信号如何从 V 区传递到 C 区，反之亦然。这篇综述认为，有足够的证据可以重新审视抗体的结构-功能关系。抗体异构研究的这些进展将为以简单和高度可预测的方式调节抗体功能提供蓝图。对抗体异构的更多关注必将有利于生物技术领域的抗体工程和疫苗设计。
{"title":"A non-classical view of antibody properties: Allosteric effect between variable and constant regions","authors":"Xiaoting Yu , Huiling Zhang , Tao Zhou , Kangliang Pan , Sayed Haidar Abbas Raza , Xing Shen , Hongtao Lei","doi":"10.1016/j.biotechadv.2024.108482","DOIUrl":"10.1016/j.biotechadv.2024.108482","url":null,"abstract":"<div><div>Historically, antibodies have been divided into two functionally independent domains, the variable (V) region for antigen binding and the constant (C) region for mediating effector functions. However, this classical view of antibody function has been severely challenged by a large and growing number of studies, which reveal long-range conformational interactions and allosteric links between the V and C regions. This review comprehensively summarizes the existing studies on antibody allostery, including allosteric conformational changes induced by covalent modifications or noncovalent ligand binding. In addition, we discuss how intramolecular allosteric signals are transmitted from the V to C regions and <em>vice versa</em>. This review argues that there is sufficient evidence to revisit the structure-function relationship of antibodies. These advances in antibody allostery will provide a blueprint for regulating antibody functions in a simple and highly predictable manner. More focus on antibody allostery will definitely benefit antibody engineering and vaccine design in the field of biotechnology.</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"78 ","pages":"Article 108482"},"PeriodicalIF":12.1,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-20DOI: 10.1016/j.biotechadv.2024.108483
Di Cheng , Yi Guo , Jixing Lyu , Yang Liu , Wenhao Xu , Weiyi Zheng , Yuchen Wang , Pei Qiao
Native mass spectrometry (nMS) is becoming a crucial tool for analyzing membrane proteins (MPs), yet challenges remain in solubilizing and stabilizing their native conformations while resolving and characterizing the heterogeneity introduced by post-translational modifications and ligand binding. This review highlights recent advancements and persistent challenges in preparing MPs for nMS. Optimizing detergents and additives can significantly reduce sample heterogeneity and surface charge, enhancing MP signal quality and structural preservation in nMS. A strategic workflow incorporating affinity capture, stabilization agents, and size-exclusion chromatography to remove unfolded species demonstrates success in improving nMS characterization. Continued development of customized detergents and reagents tailored for specific MPs may further minimize heterogeneity and boost signals. Instrumental advances are also needed to elucidate more dynamically complex and labile MPs. Effective sample preparation workflows may provide insights into MP structures, dynamics, and interactions underpinning membrane biology. With ongoing methodological innovation, nMS shows promise to complement biophysical studies and facilitate drug discovery targeting this clinically important yet technically demanding protein class.
{"title":"Advances and challenges in preparing membrane proteins for native mass spectrometry","authors":"Di Cheng , Yi Guo , Jixing Lyu , Yang Liu , Wenhao Xu , Weiyi Zheng , Yuchen Wang , Pei Qiao","doi":"10.1016/j.biotechadv.2024.108483","DOIUrl":"10.1016/j.biotechadv.2024.108483","url":null,"abstract":"<div><div>Native mass spectrometry (nMS) is becoming a crucial tool for analyzing membrane proteins (MPs), yet challenges remain in solubilizing and stabilizing their native conformations while resolving and characterizing the heterogeneity introduced by post-translational modifications and ligand binding. This review highlights recent advancements and persistent challenges in preparing MPs for nMS. Optimizing detergents and additives can significantly reduce sample heterogeneity and surface charge, enhancing MP signal quality and structural preservation in nMS. A strategic workflow incorporating affinity capture, stabilization agents, and size-exclusion chromatography to remove unfolded species demonstrates success in improving nMS characterization. Continued development of customized detergents and reagents tailored for specific MPs may further minimize heterogeneity and boost signals. Instrumental advances are also needed to elucidate more dynamically complex and labile MPs. Effective sample preparation workflows may provide insights into MP structures, dynamics, and interactions underpinning membrane biology. With ongoing methodological innovation, nMS shows promise to complement biophysical studies and facilitate drug discovery targeting this clinically important yet technically demanding protein class.</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"78 ","pages":"Article 108483"},"PeriodicalIF":12.1,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142684169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-20DOI: 10.1016/j.biotechadv.2024.108479
Yuhan Zhang , Jianxiao Zhao , Xi Sun , Yangyang Zheng , Tao Chen , Zhiwen Wang
Transcriptional regulatory networks (TRNs) play a crucial role in exploring microbial life activities and complex regulatory mechanisms. The comprehensive reconstruction of TRNs requires the integration of large-scale experimental data, which poses significant challenges due to the complexity of regulatory relationships. The application of machine learning tools, such as clustering analysis, has been employed to investigate TRNs, but these methods have limitations in capturing both global and local co-expression effects. In contrast, Independent Component Analysis (ICA) has emerged as a powerful analysis algorithm for modularizing independently regulated gene sets in TRNs, allowing it to account for both global and local co-expression effects. In this review, we comprehensively summarize the application of ICA in unraveling TRNs and highlight the research progress in three key aspects: (1) extending TRNs with iModulon analysis; (2) elucidating the regulatory mechanisms triggered by environmental perturbation; and (3) exploring the mechanisms of transcriptional regulation triggered by changes in microbial physiological state. At the end of this review, we also address the challenges facing ICA in TRN analysis and outline future research directions to promote the advancement of ICA-based transcriptomics analysis in biotechnology and related fields.
{"title":"Leveraging independent component analysis to unravel transcriptional regulatory networks: A critical review and future directions","authors":"Yuhan Zhang , Jianxiao Zhao , Xi Sun , Yangyang Zheng , Tao Chen , Zhiwen Wang","doi":"10.1016/j.biotechadv.2024.108479","DOIUrl":"10.1016/j.biotechadv.2024.108479","url":null,"abstract":"<div><div>Transcriptional regulatory networks (TRNs) play a crucial role in exploring microbial life activities and complex regulatory mechanisms. The comprehensive reconstruction of TRNs requires the integration of large-scale experimental data, which poses significant challenges due to the complexity of regulatory relationships. The application of machine learning tools, such as clustering analysis, has been employed to investigate TRNs, but these methods have limitations in capturing both global and local co-expression effects. In contrast, Independent Component Analysis (ICA) has emerged as a powerful analysis algorithm for modularizing independently regulated gene sets in TRNs, allowing it to account for both global and local co-expression effects. In this review, we comprehensively summarize the application of ICA in unraveling TRNs and highlight the research progress in three key aspects: (1) extending TRNs with iModulon analysis; (2) elucidating the regulatory mechanisms triggered by environmental perturbation; and (3) exploring the mechanisms of transcriptional regulation triggered by changes in microbial physiological state. At the end of this review, we also address the challenges facing ICA in TRN analysis and outline future research directions to promote the advancement of ICA-based transcriptomics analysis in biotechnology and related fields.</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"78 ","pages":"Article 108479"},"PeriodicalIF":12.1,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-19DOI: 10.1016/j.biotechadv.2024.108480
Hossein Kavoni , Iman Shahidi Pour Savizi , Nathan E. Lewis , Seyed Abbas Shojaosadati
The production of monoclonal antibodies (mAbs) using Chinese Hamster Ovary (CHO) cells has revolutionized the treatment of numerous diseases, solidifying their position as a cornerstone of the biopharmaceutical industry. However, achieving maximum mAb production while upholding strict product quality standards remains a significant hurdle. Optimizing cell culture media emerges as a critical factor in this endeavor, requiring a nuanced understanding of the complex interplay of nutrients, growth factors, and other components that profoundly influence cellular growth, productivity, and product quality. Significant strides have been made in media optimization, including techniques such as media blending, one factor at a time, and statistical design of experiments approaches. The present review provides a comprehensive analysis of the recent advancements in culture media design strategies, focusing on the comparative application of systems biology (SB) and machine learning (ML) approaches. The applications of SB and ML in optimizing CHO cell culture medium and successful examples of their use are summarized. Finally, we highlight the immense potential of integrating SB and ML, emphasizing the development of hybrid models that leverage the strengths of both approaches for robust, efficient, and scalable optimization of mAb production in CHO cells. This review provides a roadmap for researchers and industry professionals to navigate the complex landscape of mAb production optimization, paving the way for developing next-generation CHO cell culture media that drive significant improvements in yield and productivity.
利用中国仓鼠卵巢（CHO）细胞生产单克隆抗体（mAb）为众多疾病的治疗带来了革命性的变化，巩固了其作为生物制药行业基石的地位。然而，如何在保证严格的产品质量标准的同时实现最大的 mAb 产量仍然是一个重大障碍。优化细胞培养基是这一努力的关键因素，需要对营养物质、生长因子和其他成分的复杂相互作用有细致入微的了解，这些成分对细胞生长、生产率和产品质量有着深远的影响。在培养基优化方面已经取得了长足的进步，包括培养基混合、一次一个因子和统计实验设计方法等技术。本综述全面分析了培养基设计策略的最新进展，重点是系统生物学（SB）和机器学习（ML）方法的比较应用。综述了系统生物学（SB）和机器学习（ML）方法在优化 CHO 细胞培养基方面的应用及其成功案例。最后，我们强调了整合 SB 和 ML 的巨大潜力，强调开发混合模型，利用两种方法的优势，稳健、高效、可扩展地优化 CHO 细胞中 mAb 的生产。这篇综述为研究人员和业界专业人士提供了一个路线图，帮助他们驾驭 mAb 生产优化的复杂局面，为开发新一代 CHO 细胞培养基铺平道路，从而显著提高产量和生产率。
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Pub Date : 2024-11-17DOI: 10.1016/j.biotechadv.2024.108478
Ya-Jun Liu , Xiaoqing Wang , Yuman Sun , Yingang Feng
In bacteria, where gene transcription and translation occur concurrently, post-transcriptional regulation is acknowledged to be effective and precise. The 5′ untranslated regions (5′ UTRs) typically harbor diverse post-transcriptional regulatory elements, like riboswitches, RNA thermometers, small RNAs, and upstream open reading frames, that serve to modulate transcription termination, translation initiation, and mRNA stability. Consequently, exploring 5′ UTR-derived regulatory elements is vital for synthetic biology and metabolic engineering. Over the past few years, the investigation of successive mechanisms has facilitated the development of various genetic tools from bacterial 5′ UTRs. This review consolidates current understanding of 5′ UTR regulatory functions, presents recent progress in 5′ UTR-element design and screening, updates the tools and regulatory strategies developed, and highlights the challenges and necessity of establishing reliable bioinformatic analysis methods and non-model bacterial chassis in the future.
{"title":"Bacterial 5′ UTR: A treasure-trove for post-transcriptional regulation","authors":"Ya-Jun Liu , Xiaoqing Wang , Yuman Sun , Yingang Feng","doi":"10.1016/j.biotechadv.2024.108478","DOIUrl":"10.1016/j.biotechadv.2024.108478","url":null,"abstract":"<div><div>In bacteria, where gene transcription and translation occur concurrently, post-transcriptional regulation is acknowledged to be effective and precise. The 5′ untranslated regions (5′ UTRs) typically harbor diverse post-transcriptional regulatory elements, like riboswitches, RNA thermometers, small RNAs, and upstream open reading frames, that serve to modulate transcription termination, translation initiation, and mRNA stability. Consequently, exploring 5′ UTR-derived regulatory elements is vital for synthetic biology and metabolic engineering. Over the past few years, the investigation of successive mechanisms has facilitated the development of various genetic tools from bacterial 5′ UTRs. This review consolidates current understanding of 5′ UTR regulatory functions, presents recent progress in 5′ UTR-element design and screening, updates the tools and regulatory strategies developed, and highlights the challenges and necessity of establishing reliable bioinformatic analysis methods and non-model bacterial chassis in the future.</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"78 ","pages":"Article 108478"},"PeriodicalIF":12.1,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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