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Mapping multipathology via spatial omic integration 通过空间基因组整合映射多病理。
IF 7 2区 工程技术 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-12-09 DOI: 10.1016/j.copbio.2025.103398
Ryan Palaganas , Dimitrios N Sidiropoulos , Meaghan Morris , Genevieve L Stein-O’Brien
Neurodegenerative diseases (NDDs) are a global health crisis affecting 15% of the population, with projections indicating this burden will double within two decades. Despite having shared molecular hallmarks, co-occurring proteinopathies, predictable progression patterns, and overlapping genetic risk variants, what causes specific NDDs to manifest in a particular individual or even a particular cell type is unknown. Thus, systems biology approaches are necessary to decipher the molecular, cellular, and environmental interactions driving pathogenesis. Multi-omics spatial profiling preserves tissue architecture while mapping cellular phenotypes and molecular interactions at subcellular resolution. Systems biology integration of these modalities will facilitate the identification of underlying causes of neuronal vulnerability, protein aggregation mechanisms, and disease progression patterns, accelerating targeted therapeutic development across NDDs.
神经退行性疾病(ndd)是影响15%人口的全球健康危机,预测表明这一负担将在20年内翻一番。尽管具有共同的分子特征、共同发生的蛋白质病变、可预测的进展模式和重叠的遗传风险变异,但导致特定ndd在特定个体甚至特定细胞类型中表现出来的原因尚不清楚。因此,系统生物学的方法是必要的,以破译分子,细胞和环境的相互作用驱动发病机制。多组学空间分析保留组织结构,同时在亚细胞分辨率下绘制细胞表型和分子相互作用。这些模式的系统生物学整合将有助于识别神经元易感性的潜在原因、蛋白质聚集机制和疾病进展模式,加速ndd的靶向治疗开发。
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引用次数: 0
Molecular machines from individuals to swarms 从个体到群体的分子机器。
IF 7 2区 工程技术 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-12-09 DOI: 10.1016/j.copbio.2025.103400
Bin Wang , Yuan Lu
Molecular machines convert physical and chemical energy into effective mechanical work, and have made significant progress as tools capable of micro- and nano-scale smart manipulation in fields such as medicine, catalysis, and materials. However, functional limitations hinder the rapid iteration of molecular machines toward practical applications. This requires not only the individual design of molecular machines to achieve more efficient performance in diverse systems but also the cooperation of molecular machines through a swarm to integrate spatial and temporal aspects, thereby scaling up molecular-scale deformations to macroscopic work. In this review, we discuss the latest achievements in individual and swarm design of molecular machines, address existing challenges, and provide insights into the future development of these machines.
分子机器将物理和化学能转化为有效的机械功,作为能够在医学、催化和材料等领域进行微纳米级智能操作的工具,已经取得了重大进展。然而,功能限制阻碍了分子机器向实际应用的快速迭代。这不仅需要分子机器的个性化设计以在不同的系统中实现更高效的性能,还需要分子机器通过群体的合作来整合空间和时间方面,从而将分子尺度的变形扩展到宏观工作。本文综述了分子机器的个体设计和群体设计的最新进展,指出了存在的挑战,并对分子机器的未来发展提出了展望。
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引用次数: 0
Deep learning and generative artificial intelligence methods in enzyme and cell engineering 酶和细胞工程中的深度学习和生成式人工智能方法。
IF 7 2区 工程技术 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-12-04 DOI: 10.1016/j.copbio.2025.103393
Steffen Docter , Benoit David , Holger Gohlke
Efficient enzymes and microbial factories are essential to promote the transition toward a sustainable bioeconomy. This review focuses on the progress of artificial intelligence (AI) methods in accelerating the development of optimized biocatalysts and genetic networks in cells. Recent advances in AI in the field of enzyme discovery, engineering, and de novo design are discussed. Additionally, we highlight examples of successful applications of AI in optimizing different components in cells, from gene expression regulation to metabolic pathway optimization and design. Finally, this review emphasizes the challenges limiting the reliability and generalizability of current AI methods.
高效的酶和微生物工厂对于促进向可持续生物经济的过渡至关重要。本文综述了人工智能(AI)方法在加速优化生物催化剂和细胞遗传网络开发方面的进展。讨论了人工智能在酶发现、工程和从头设计领域的最新进展。此外,我们还重点介绍了人工智能在优化细胞中不同成分方面的成功应用,从基因表达调控到代谢途径优化和设计。最后,本综述强调了限制当前人工智能方法可靠性和通用性的挑战。
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引用次数: 0
Tools for automated genome editing of stem cells 干细胞自动基因组编辑工具
IF 7 2区 工程技术 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-12-04 DOI: 10.1016/j.copbio.2025.103399
Bastian Nießing , Rebekka Wagner , Laura Herbst , Robert H Schmitt
Automated genome editing of stem cells represents a great advancement in the fields of disease modeling and regenerative medicine. This review evaluates the current tools and methodologies for implementing automated genome editing for induced pluripotent stem cells. The increasing demand for precise genome editing technologies, driven by the growing gene editing market, necessitates efficient and scalable solutions to overcome the complexities and costs associated with traditional editing methods. A comprehensive overview of various automation strategies is provided, focusing on key workflows that encompass stem cell expansion, genetic material delivery through viral vectors, lipid nanoparticles, and electroporation, as well as monoclonal expansion techniques. Advances in automation not only enhance editing efficiency and reduce labor intensity but also ensure quality and reproducibility in stem cell research. As the field progresses, the integration of artificial intelligence and the shift toward closed, good manufacturing practice-compliant systems are anticipated to further streamline automated genome editing processes.
干细胞的自动基因组编辑代表了疾病建模和再生医学领域的巨大进步。这篇综述评估了目前对诱导多能干细胞实施自动基因组编辑的工具和方法。在不断增长的基因编辑市场的推动下,对精确基因组编辑技术的需求不断增加,需要有效和可扩展的解决方案来克服传统编辑方法的复杂性和成本。提供了各种自动化策略的全面概述,重点关注关键工作流程,包括干细胞扩增,通过病毒载体传递遗传物质,脂质纳米颗粒和电穿孔,以及单克隆扩增技术。自动化的进步不仅提高了编辑效率,降低了劳动强度,而且保证了干细胞研究的质量和可重复性。随着该领域的发展,人工智能的整合和向封闭的、符合良好生产规范的系统的转变预计将进一步简化自动化基因组编辑过程。
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引用次数: 0
Design of DNA strand displacement reactions DNA链置换反应的设计
IF 7 2区 工程技术 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-12-04 DOI: 10.1016/j.copbio.2025.103396
Križan Jurinović, Merry Mitra, Rakesh Mukherjee, Thomas E Ouldridge
DNA strand displacement (SD) reactions are central to the operation of many synthetic nucleic acid systems, including molecular circuits, sensors, and machines. Over the years, a broad set of design frameworks has emerged to accommodate various functional goals, initial configurations, and environmental conditions. Nevertheless, key challenges persist, particularly in reliably predicting reaction kinetics. In contrast to reviews centred on network-level architectures, this article focuses on the design and analysis of individual SD reactions, highlighting kinetic mechanisms, structural determinants, and the current limits of predictive modelling. We identify promising innovations while analysing the factors that continue to hinder predictive accuracy. We conclude by outlining future directions for achieving more robust and programmable behaviour in DNA-based systems.
DNA链位移(SD)反应是许多合成核酸系统操作的核心,包括分子电路、传感器和机器。多年来,出现了一系列广泛的设计框架,以适应各种功能目标、初始配置和环境条件。然而,关键的挑战仍然存在,特别是在可靠地预测反应动力学方面。与以网络级架构为中心的综述相反,本文侧重于单个SD反应的设计和分析,强调动力学机制,结构决定因素以及预测建模的当前局限性。我们确定了有前途的创新,同时分析了继续阻碍预测准确性的因素。最后,我们概述了在基于dna的系统中实现更健壮和可编程行为的未来方向。
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引用次数: 0
Design principles for adaptive and evolving engineered living materials 适应性和进化工程生物材料的设计原则。
IF 7 2区 工程技术 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-12-03 DOI: 10.1016/j.copbio.2025.103397
Yifan Cui , Mark W Tibbitt , Timothy K Lu , Tzu-Chieh Tang
Engineered living materials (ELMs) combine living cells, typically microorganisms, such as bacteria, yeasts, or filamentous fungi, with structural carrier matrices to form systems capable of sensing, growth, and self-repair. Most current designs emphasize programming the microbes to render otherwise static materials functional. A less explored dimension is leveraging reciprocal microbial–material interactions themselves to engineer adaptive and evolving living materials as integrated systems. Achieving such dynamic behavior requires understanding how support matrices influence microbial behavior and how cells, in turn, reshape material properties over time. This review outlines key modes of cell–material interactions as a framework for expanding the functional toolbox of ELMs and for creating sustainable and programmable materials that respond to their environments and evolve.
工程活材料(elm)将活细胞(通常是微生物,如细菌、酵母或丝状真菌)与结构载体基质结合起来,形成能够感知、生长和自我修复的系统。目前的大多数设计都强调对微生物进行编程,以使其他静态材料发挥功能。一个较少探索的维度是利用微生物与物质相互作用本身来设计适应性和进化的生物材料作为集成系统。实现这种动态行为需要了解支持基质如何影响微生物行为,以及细胞如何随着时间的推移重塑材料特性。这篇综述概述了细胞-材料相互作用的关键模式,作为扩展elm功能工具箱的框架,并用于创建响应环境和进化的可持续和可编程材料。
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引用次数: 0
Molecular diagnostics for infectious disease and cancer based on glass capillary nanopore sensing 基于玻璃毛细管纳米孔传感的传染病和癌症分子诊断。
IF 7 2区 工程技术 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-11-29 DOI: 10.1016/j.copbio.2025.103394
Ryogo Higashi , Izumi Shibayama , Jiajue Ji , Tao Ren , Iiro Kiiski , Nanami Takeuchi , Ryuji Kawano
Glass capillary nanopores have been widely used for resistive pulse sensing and ionic current rectification-based nanopore sensing due to their excellent mechanical properties, simple fabrication, easy surface modification, and low production cost. These nanopores have demonstrated great potential in detecting diverse biomarkers, including nucleic acids, proteins, cell vesicles, viruses, and bacteria. Here, we highlight recent advances in molecular diagnostics using glass capillary nanopores, especially focusing on the detection of infectious disease pathogens and cancer-associated microRNAs. By integrating precisely sized glass nanopipette-based nanopores with nucleic acid amplification techniques and well-designed probes, this sensing platform has emerged as a promising method for liquid biopsy from patient body fluids. In consideration of recent research on molecular diagnostics and the difficulties with glass capillary nanopipettes, we also discuss the future direction of molecular diagnostics using this tool.
玻璃毛细管纳米孔由于其优异的力学性能、制作简单、表面改性容易、生产成本低等优点,在电阻式脉冲传感和离子电流整流传感中得到了广泛的应用。这些纳米孔在检测各种生物标志物方面显示出巨大的潜力,包括核酸、蛋白质、细胞囊泡、病毒和细菌。在这里,我们重点介绍了利用玻璃毛细管纳米孔进行分子诊断的最新进展,特别是在传染病病原体和癌症相关microrna的检测方面。通过将精确尺寸的基于玻璃纳米管的纳米孔与核酸扩增技术和精心设计的探针相结合,该传感平台已成为一种有前途的从患者体液中进行液体活检的方法。考虑到分子诊断的最新研究和玻璃毛细管纳米吸管的困难,我们还讨论了使用该工具进行分子诊断的未来方向。
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引用次数: 0
Advances and critical evaluation of autonomous protein engineering: towards transparent, accessible, and reproducible platforms 自主蛋白工程的进展和关键评价:走向透明,可访问和可复制的平台
IF 7 2区 工程技术 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-11-28 DOI: 10.1016/j.copbio.2025.103395
Konstantin FG Weigmann, Uwe T Bornscheuer, Mark Doerr
Protein engineering aims to enhance enzymatic properties such as activity, selectivity, stability, and solvent tolerance by restructuring protein frameworks beyond natural performance limits. This process relies on the iterative Design-Build-Test-Learn cycle, where experimental feedback guides progressive improvements. Advancements in artificial intelligence have transformed both the Design and Learn phases, with zero-shot protein language models predicting beneficial mutations directly from sequence data and supervised models integrating assay results to refine subsequent variant designs. These approaches reduce the dependence on structural insights while enabling the discovery of synergistic effects across mutations. Automation technologies, including robotic liquid handlers and integrated platforms, have become central to modern protein engineering by reducing errors, ensuring reproducibility, and enabling large-scale variant screening. Emerging autonomous platforms demonstrate closed-loop optimization that couples protein library design, automated plasmid transformation/protein expression and corresponding assays, and machine learning–driven decision-making. These systems achieve significant accelerations in the research process, reducing multi-round engineering cycles from months to days while successfully improving diverse proteins/enzymes to a targeted objective. Beyond single-lab platforms, orchestration frameworks adhering to FAIR data principles and leveraging knowledge graphs promise distributed ‘self-driving’ laboratories capable of coordinating workflows across facilities. While high setup costs and proprietary systems remain challenging, open-source and modular alternatives highlight a path toward transparent, flexible automation. Collectively, these innovations are redefining protein engineering as an increasingly autonomous, data-driven discipline.
蛋白质工程旨在通过重组蛋白质框架来提高酶的活性、选择性、稳定性和溶剂耐受性。这个过程依赖于设计-构建-测试-学习的迭代循环,在这个循环中,实验反馈指导着渐进式改进。人工智能的进步已经改变了设计和学习阶段,零shot蛋白质语言模型直接从序列数据预测有益的突变,监督模型整合分析结果来完善后续的变体设计。这些方法减少了对结构洞察力的依赖,同时使发现跨突变的协同效应成为可能。自动化技术,包括机器人液体处理和集成平台,通过减少错误、确保可重复性和实现大规模变异筛选,已经成为现代蛋白质工程的核心。新兴的自主平台展示了蛋白质库设计、自动质粒转化/蛋白质表达和相应检测以及机器学习驱动决策的闭环优化。这些系统在研究过程中实现了显著的加速,将多轮工程周期从几个月缩短到几天,同时成功地将多种蛋白质/酶改善到目标目标。除了单一实验室平台之外,遵循FAIR数据原则和利用知识图谱的编排框架承诺能够跨设施协调工作流程的分布式“自动驾驶”实验室。虽然高昂的安装成本和专有系统仍然具有挑战性,但开源和模块化替代方案突出了通往透明、灵活自动化的道路。总的来说,这些创新正在将蛋白质工程重新定义为一门越来越自主、数据驱动的学科。
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引用次数: 0
Perspectives for artificial intelligence in bioprocess automation 人工智能在生物过程自动化中的应用前景
IF 7 2区 工程技术 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-11-28 DOI: 10.1016/j.copbio.2025.103392
Laura Marie Helleckes , Sebastian Putz , Kshitiz Gupta , Matthias Franzreb , Hector Garcia Martin
Recent advances in artificial intelligence (AI) have rapidly changed the lab automation landscape, promoting self-driving laboratories (SDLs) that enable autonomous scientific discovery. These trends are increasingly applied in bioprocess development, yet bioprocessing faces unique challenges — biological complexity, regulatory and safety requirements, and multiscale experimentation — that distinguish it from other automation domains. Rather than pursuing full autonomy, we foresee that hybrid SDLs, combining AI-driven decision-making with sustained human oversight, represent the most practical near-term trajectory. This review examines three interconnected perspectives: (i) hybrid human–machine decision-making for bioprocessing; (ii) laboratory design considerations in the era of AI; and (iii) scale-up challenges when transitioning from screening to manufacturing. We highlight critical gaps in data standardization and the required community efforts necessary to realize autonomous bioprocess innovation.
人工智能(AI)的最新进展迅速改变了实验室自动化的格局,推动了能够自主科学发现的自动驾驶实验室(sdl)的发展。这些趋势越来越多地应用于生物工艺开发,但生物加工面临着独特的挑战-生物复杂性,监管和安全要求,以及多尺度实验-将其与其他自动化领域区分开来。我们预计,混合sdl(将人工智能驱动的决策与持续的人类监督相结合)将代表最实用的近期发展轨迹,而不是追求完全自主。本文综述了三个相互关联的观点:(i)生物加工的混合人机决策;(ii)人工智能时代的实验室设计考量;(三)从筛选过渡到生产时的规模挑战。我们强调了数据标准化方面的关键差距,以及实现自主生物工艺创新所需的社区努力。
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引用次数: 0
Resource allocation models: theory and applications in microbial biotechnology 资源配置模型:微生物生物技术的理论与应用
IF 7 2区 工程技术 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-11-24 DOI: 10.1016/j.copbio.2025.103391
Bas Teusink , Pranas Grigaitis , Maaike Remeijer , Frank Bruggeman , Ralf Steuer
Wild-type cells allocate their limited resources to express proteins that support growth and survival in their natural environments. In contrast, biotechnology aims to maximize key performance indicators such as yield, productivity, or titer. Maximizing performance indicators, however, inevitably encounters physical, biochemical, genetic, and evolutionary constraints that create trade-offs between competing objectives. A central challenge in microbial biotechnology is therefore to align cellular behavior with production goals, which can be achieved by manipulating cultivation conditions and intracellular resource allocation strategies through targeted metabolic engineering or adaptive laboratory evolution. Resource allocation models provide a theoretical framework to understand and guide such optimization efforts. Here, we review the current state of resource allocation modeling, including tools, methods, and theoretical foundations, and discuss their current applications in microbial biotechnology.
野生型细胞将其有限的资源分配给表达在自然环境中支持生长和生存的蛋白质。相反,生物技术的目标是最大限度地提高关键性能指标,如产量、生产力或滴度。然而,最大化性能指标不可避免地会遇到物理的、生化的、遗传的和进化的限制,这些限制会在相互竞争的目标之间产生权衡。因此,微生物生物技术的核心挑战是使细胞行为与生产目标保持一致,这可以通过有针对性的代谢工程或适应性实验室进化来操纵培养条件和细胞内资源分配策略来实现。资源分配模型为理解和指导这种优化工作提供了理论框架。本文综述了资源配置建模的现状,包括工具、方法和理论基础,并讨论了它们在微生物生物技术中的应用现状。
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引用次数: 0
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Current opinion in biotechnology
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