首页 > 最新文献

Frontiers in systems biology最新文献

英文 中文
Transporter annotations are holding up progress in metabolic modeling 转运体注释阻碍了代谢建模的进展
Pub Date : 2024-07-24 DOI: 10.3389/fsysb.2024.1394084
John Casey, Brian Bennion, Patrik D’haeseleer, Jeffrey Kimbrel, G. Marschmann, Ali Navid
Mechanistic, constraint-based models of microbial isolates or communities are a staple in the metabolic analysis toolbox, but predictions about microbe-microbe and microbe-environment interactions are only as good as the accuracy of transporter annotations. A number of hurdles stand in the way of comprehensive functional assignments for membrane transporters. These include general or non-specific substrate assignments, ambiguity in the localization, directionality and reversibility of a transporter, and the many-to-many mapping of substrates, transporters and genes. In this perspective, we summarize progress in both experimental and computational approaches used to determine the function of transporters and consider paths forward that integrate both. Investment in accurate, high-throughput functional characterization is needed to train the next-generation of predictive tools toward genome-scale metabolic network reconstructions that better predict phenotypes and interactions. More reliable predictions in this domain will benefit fields ranging from personalized medicine to metabolic engineering to microbial ecology.
微生物分离或群落的机制性、基于约束的模型是代谢分析工具箱中的主要工具,但对微生物-微生物和微生物-环境相互作用的预测只能与转运体注释的准确性相匹配。在对膜转运体进行全面的功能分配时会遇到许多障碍。这些障碍包括一般或非特异性底物分配,转运体的定位、方向性和可逆性不明确,以及底物、转运体和基因的多对多映射。在这一视角中,我们总结了用于确定转运体功能的实验和计算方法的进展,并考虑了将两者结合起来的前进道路。需要对准确的高通量功能表征进行投资,以训练下一代预测工具,实现基因组规模的代谢网络重建,从而更好地预测表型和相互作用。该领域更可靠的预测将使个性化医学、代谢工程和微生物生态学等领域受益。
{"title":"Transporter annotations are holding up progress in metabolic modeling","authors":"John Casey, Brian Bennion, Patrik D’haeseleer, Jeffrey Kimbrel, G. Marschmann, Ali Navid","doi":"10.3389/fsysb.2024.1394084","DOIUrl":"https://doi.org/10.3389/fsysb.2024.1394084","url":null,"abstract":"Mechanistic, constraint-based models of microbial isolates or communities are a staple in the metabolic analysis toolbox, but predictions about microbe-microbe and microbe-environment interactions are only as good as the accuracy of transporter annotations. A number of hurdles stand in the way of comprehensive functional assignments for membrane transporters. These include general or non-specific substrate assignments, ambiguity in the localization, directionality and reversibility of a transporter, and the many-to-many mapping of substrates, transporters and genes. In this perspective, we summarize progress in both experimental and computational approaches used to determine the function of transporters and consider paths forward that integrate both. Investment in accurate, high-throughput functional characterization is needed to train the next-generation of predictive tools toward genome-scale metabolic network reconstructions that better predict phenotypes and interactions. More reliable predictions in this domain will benefit fields ranging from personalized medicine to metabolic engineering to microbial ecology.","PeriodicalId":73109,"journal":{"name":"Frontiers in systems biology","volume":"43 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141807065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Life’s building blocks: the modular path to multiscale complexity 生命的构件:通向多尺度复杂性的模块化道路
Pub Date : 2024-07-17 DOI: 10.3389/fsysb.2024.1417800
Saúl Huitzil, Cristián Huepe
Modularity, the structuring of systems into discrete, interconnected units, is a fundamental organizing principle in biology across multiple scales. Recent progress in understanding the role of modularity as an evolutionary mechanism and a key driver of biological complexity has highlighted its importance in shaping the structure and function of living systems. Here, we propose a unifying framework that identifies the potential evolutionary advantages of modularity in systems ranging from molecular networks to ecologies, such as facilitating evolvability, enhancing robustness, improving information flows, and enabling the emergence of higher-level functions. Our analysis reveals the pervasiveness of modularity in living systems and highlights its crucial role in the evolution of multiscale hierarchies of increasing complexity.
模块性是指将系统结构划分为离散而又相互关联的单元,是生物学中跨尺度的基本组织原则。最近,人们在理解模块性作为一种进化机制和生物复杂性的关键驱动力的作用方面取得了进展,这凸显了模块性在塑造生命系统的结构和功能方面的重要性。在这里,我们提出了一个统一的框架,以确定模块性在从分子网络到生态等系统中的潜在进化优势,如促进可进化性、增强稳健性、改善信息流以及促成更高层次功能的出现。我们的分析揭示了模块性在生命系统中的普遍性,并强调了模块性在复杂性不断增加的多尺度层次结构进化过程中的关键作用。
{"title":"Life’s building blocks: the modular path to multiscale complexity","authors":"Saúl Huitzil, Cristián Huepe","doi":"10.3389/fsysb.2024.1417800","DOIUrl":"https://doi.org/10.3389/fsysb.2024.1417800","url":null,"abstract":"Modularity, the structuring of systems into discrete, interconnected units, is a fundamental organizing principle in biology across multiple scales. Recent progress in understanding the role of modularity as an evolutionary mechanism and a key driver of biological complexity has highlighted its importance in shaping the structure and function of living systems. Here, we propose a unifying framework that identifies the potential evolutionary advantages of modularity in systems ranging from molecular networks to ecologies, such as facilitating evolvability, enhancing robustness, improving information flows, and enabling the emergence of higher-level functions. Our analysis reveals the pervasiveness of modularity in living systems and highlights its crucial role in the evolution of multiscale hierarchies of increasing complexity.","PeriodicalId":73109,"journal":{"name":"Frontiers in systems biology","volume":" 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141830810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Coupling quantitative systems pharmacology modelling to machine learning and artificial intelligence for drug development: its pAIns and gAIns 将定量系统药理学建模与机器学习和人工智能相结合,促进药物开发:其 pAIns 和 gAIns
Pub Date : 2024-07-12 DOI: 10.3389/fsysb.2024.1380685
Núria Folguera-Blasco, Florencia A. T. Boshier, Aydar Uatay, C. Pichardo-Almarza, Massimo Lai, Jacopo Biasetti, Richard Dearden, Megan Gibbs, Holly Kimko
Quantitative Systems Pharmacology (QSP) has become a powerful tool in the drug development landscape. To facilitate its continued implementation and to further enhance its applicability, a symbiotic approach in which QSP is combined with artificial intelligence (AI) and machine learning (ML) seems key. This manuscript presents four case examples where the application of a symbiotic approach could unlock new insights from multidimensional data, including real-world data, potentially leading to breakthroughs in drug development. Besides the remarkable benefits (gAIns) that the symbiosis can offer, it does also carry potential challenges (pAIns) such as how to assess and quantify uncertainty, bias and error. Hence, to ensure a successful implementation, arising pAIns need to be acknowledged and carefully addressed. Successful implementation of the symbiotic QSP and ML/AI approach has the potential to serve as a catalyst, paving the way for a paradigm shift in drug development.
定量系统药理学(QSP)已成为药物开发领域的有力工具。为促进其持续应用并进一步提高其适用性,将定量系统药理学与人工智能(AI)和机器学习(ML)相结合的共生方法似乎至关重要。本手稿介绍了四个案例,在这些案例中,应用共生方法可以从包括真实世界数据在内的多维数据中获得新的见解,从而有可能在药物开发方面取得突破。共生方法除了能带来显著的优势(gAIns)外,也存在潜在的挑战(pAIns),如如何评估和量化不确定性、偏差和误差。因此,为确保成功实施,必须认识到并认真解决由此产生的 pAIns。QSP 和 ML/AI 共生方法的成功实施有可能成为一种催化剂,为药物开发模式的转变铺平道路。
{"title":"Coupling quantitative systems pharmacology modelling to machine learning and artificial intelligence for drug development: its pAIns and gAIns","authors":"Núria Folguera-Blasco, Florencia A. T. Boshier, Aydar Uatay, C. Pichardo-Almarza, Massimo Lai, Jacopo Biasetti, Richard Dearden, Megan Gibbs, Holly Kimko","doi":"10.3389/fsysb.2024.1380685","DOIUrl":"https://doi.org/10.3389/fsysb.2024.1380685","url":null,"abstract":"Quantitative Systems Pharmacology (QSP) has become a powerful tool in the drug development landscape. To facilitate its continued implementation and to further enhance its applicability, a symbiotic approach in which QSP is combined with artificial intelligence (AI) and machine learning (ML) seems key. This manuscript presents four case examples where the application of a symbiotic approach could unlock new insights from multidimensional data, including real-world data, potentially leading to breakthroughs in drug development. Besides the remarkable benefits (gAIns) that the symbiosis can offer, it does also carry potential challenges (pAIns) such as how to assess and quantify uncertainty, bias and error. Hence, to ensure a successful implementation, arising pAIns need to be acknowledged and carefully addressed. Successful implementation of the symbiotic QSP and ML/AI approach has the potential to serve as a catalyst, paving the way for a paradigm shift in drug development.","PeriodicalId":73109,"journal":{"name":"Frontiers in systems biology","volume":"37 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141653879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Predicting chronic responses to calcium channel blockade with a virtual population of African Americans with hypertensive chronic kidney disease 利用患有高血压慢性肾病的非裔美国人虚拟人群预测钙通道阻滞剂的慢性反应
Pub Date : 2024-07-04 DOI: 10.3389/fsysb.2024.1327357
J. Clemmer, W. Pruett, Robert L. Hester
Chronic kidney disease (CKD) is associated with the progressive loss of functional nephrons and hypertension (HTN). Clinical studies demonstrate calcium channel blocker (CCB) therapy mitigates the decline in renal function in humans with essential HTN. However, there are few long-term clinical studies that determine the impact of CCBs in patients with hypertensive CKD. African Americans (AA) have a higher prevalence of CKD and a faster progression to total kidney failure as compared to the white population but the mechanisms are poorly understood. Both clinical evidence (the African American Study of Kidney Disease and Hypertension, or AASK trial) and experimental studies have demonstrated that CCB may expose glomerular capillaries to high systemic pressures and exacerbate CKD progression. Therefore, using a large physiological model, we set out to replicate the AASK trial findings, predict renal hemodynamic responses and the role of the renin-angiotensin system during CCB antihypertensive therapy in a virtual population, and hypothesize mechanisms underlying those findings. Our current mathematical model, HumMod, is comprised of integrated systems that play an integral role in long-term blood pressure (BP) control such as neural, endocrine, circulatory, and renal systems. Parameters (n = 341) that control these systems were randomly varied and resulted in 1,400 unique models that we define as a virtual population. We calibrated these models to individual patient level data from the AASK trial: BP and glomerular filtration rate (GFR) before and after 3 years of amlodipine (10 mg/day). After calibration, the new virtual population (n = 165) was associated with statistically similar BP and GFR before and after CCB. Baseline factors such as elevated single nephron GFR and low tubuloglomerular feedback were correlated with greater declines in renal function and increased glomerulosclerosis after 3 years of CCB. Blocking the renin-angiotensin system (RAS) in the virtual population decreased glomerular pressure, limited glomerular damage, and further decreased BP (−14 ± 8 mmHg) as compared to CCB alone (−11 ± 9 mmHg). Our simulations echo the potential risk of CCB monotherapy in AA CKD patients and support blockade of the renin angiotensin system as a valuable tool in renal disease treatment when combined with CCB therapy.
慢性肾脏病(CKD)与功能性肾小球的逐渐丧失和高血压(HTN)有关。临床研究表明,钙通道阻滞剂(CCB)治疗可减轻本质性高血压患者肾功能的衰退。然而,很少有长期临床研究能确定钙通道阻滞剂对高血压慢性肾脏病患者的影响。与白人相比,非裔美国人(AA)患慢性肾功能衰竭的发病率更高,发展为全肾衰竭的速度更快,但对其发病机制却知之甚少。临床证据(非裔美国人肾脏病和高血压研究,或 AASK 试验)和实验研究都表明,CCB 可能会使肾小球毛细血管暴露于较高的系统压力下,并加剧 CKD 的进展。因此,我们利用大型生理模型复制了 AASK 试验结果,预测了虚拟人群在 CCB 降压治疗期间的肾血流动力学反应和肾素-血管紧张素系统的作用,并假设了这些结果的内在机制。我们目前的数学模型 HumMod 由神经、内分泌、循环和肾脏系统等在长期血压(BP)控制中发挥重要作用的综合系统组成。控制这些系统的参数(n = 341)被随机改变,从而产生了 1400 个独特的模型,我们将其定义为虚拟群体。我们根据 AASK 试验中的单个患者数据对这些模型进行了校准:使用氨氯地平(10 毫克/天)3 年前后的血压和肾小球滤过率 (GFR)。校准后,新的虚拟人群(n = 165)在服用 CCB 前后的血压和肾小球滤过率在统计学上相似。单肾小球 GFR 升高和肾小管-肾小球低反馈等基线因素与 CCB 3 年后肾功能下降幅度增大和肾小球硬化加重相关。在虚拟人群中阻断肾素-血管紧张素系统(RAS)可降低肾小球压力,限制肾小球损伤,并进一步降低血压(-14 ± 8 mmHg),与单用 CCB 相比(-11 ± 9 mmHg)。我们的模拟结果反映了 AA CKD 患者单用 CCB 治疗的潜在风险,并支持在联合 CCB 治疗时将阻断肾素血管紧张素系统作为治疗肾病的重要工具。
{"title":"Predicting chronic responses to calcium channel blockade with a virtual population of African Americans with hypertensive chronic kidney disease","authors":"J. Clemmer, W. Pruett, Robert L. Hester","doi":"10.3389/fsysb.2024.1327357","DOIUrl":"https://doi.org/10.3389/fsysb.2024.1327357","url":null,"abstract":"Chronic kidney disease (CKD) is associated with the progressive loss of functional nephrons and hypertension (HTN). Clinical studies demonstrate calcium channel blocker (CCB) therapy mitigates the decline in renal function in humans with essential HTN. However, there are few long-term clinical studies that determine the impact of CCBs in patients with hypertensive CKD. African Americans (AA) have a higher prevalence of CKD and a faster progression to total kidney failure as compared to the white population but the mechanisms are poorly understood. Both clinical evidence (the African American Study of Kidney Disease and Hypertension, or AASK trial) and experimental studies have demonstrated that CCB may expose glomerular capillaries to high systemic pressures and exacerbate CKD progression. Therefore, using a large physiological model, we set out to replicate the AASK trial findings, predict renal hemodynamic responses and the role of the renin-angiotensin system during CCB antihypertensive therapy in a virtual population, and hypothesize mechanisms underlying those findings. Our current mathematical model, HumMod, is comprised of integrated systems that play an integral role in long-term blood pressure (BP) control such as neural, endocrine, circulatory, and renal systems. Parameters (n = 341) that control these systems were randomly varied and resulted in 1,400 unique models that we define as a virtual population. We calibrated these models to individual patient level data from the AASK trial: BP and glomerular filtration rate (GFR) before and after 3 years of amlodipine (10 mg/day). After calibration, the new virtual population (n = 165) was associated with statistically similar BP and GFR before and after CCB. Baseline factors such as elevated single nephron GFR and low tubuloglomerular feedback were correlated with greater declines in renal function and increased glomerulosclerosis after 3 years of CCB. Blocking the renin-angiotensin system (RAS) in the virtual population decreased glomerular pressure, limited glomerular damage, and further decreased BP (−14 ± 8 mmHg) as compared to CCB alone (−11 ± 9 mmHg). Our simulations echo the potential risk of CCB monotherapy in AA CKD patients and support blockade of the renin angiotensin system as a valuable tool in renal disease treatment when combined with CCB therapy.","PeriodicalId":73109,"journal":{"name":"Frontiers in systems biology","volume":" 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141679000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Specialty grand challenge: how can we use integrative approaches to understand microbial community dynamics? 专业大挑战:我们如何使用综合方法来理解微生物群落动态?
IF 2.3 Pub Date : 2024-06-17 eCollection Date: 2024-01-01 DOI: 10.3389/fsysb.2024.1432791
Umer Zeeshan Ijaz, Aqsa Ameer, Farrukh Saleem, Farzana Gul, Ciara Keating, Sundus Javed
{"title":"Specialty grand challenge: how can we use integrative approaches to understand microbial community dynamics?","authors":"Umer Zeeshan Ijaz, Aqsa Ameer, Farrukh Saleem, Farzana Gul, Ciara Keating, Sundus Javed","doi":"10.3389/fsysb.2024.1432791","DOIUrl":"10.3389/fsysb.2024.1432791","url":null,"abstract":"","PeriodicalId":73109,"journal":{"name":"Frontiers in systems biology","volume":"4 ","pages":"1432791"},"PeriodicalIF":2.3,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12342006/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144849996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
PdPANA: phagemid display as peptide array for neutralizing antibodies, an engineered in silico vaccine candidate against COVID-19. PdPANA:用于中和抗体的噬菌体肽阵列,一种针对COVID-19的工程硅疫苗候选物。
IF 2.3 Pub Date : 2024-06-17 eCollection Date: 2024-01-01 DOI: 10.3389/fsysb.2024.1309891
Javier Uzcátegui, Khaleel Mullah, Daniel Buvat de Virgini, Andrés Mendoza, Rafael Urdaneta, Alejandra Naranjo

The COVID-19 pandemic has tested the technical, scientific, and industrial resources of all countries worldwide. Faced with the absence of pharmacological strategies against the disease, an effective plan for vaccinating against SARS-CoV-2 has been essential. Due to the lack of production means and necessary infrastructure, only a few nations could adequately confront this pathogen with a production, storage, and distribution scheme in place. This disease has become endemic in many countries, especially in those that are developing, thus necessitating solutions tailored to their reality. In this paper, we propose an in silico method to guide the design towards a thermally stable, universal, efficient, and safe COVID-19 vaccine candidate against SARS-CoV-2 using bioinformatics, immunoinformatics, and molecular modeling approaches for the selection of antigens with higher immunogenic potential, incorporating them into the surface of the M13 phage. Our work focused on using phagemid display as peptide array for neutralizing antibodies (PdPANA). This alternative approach might be useful during the vaccine development process, since it could bring improvements in terms of cost-effectiveness in production, durability, and ease of distribution of the vaccine under less stringent thermal conditions compared to existing methods. Our results suggest that in the heavily glycosylated region of SARS-CoV-2 Spike protein (aa 344-583), from its inter-glycosylated regions, useful antigenic peptides can be obtained to be used in M13 phagemid display system. PdPANA, our proposed method might be useful to overcome the classic shortcoming posed by the phage-display technique (i.e., the time-consuming task of in vitro screening through great sized libraries with non-useful recombinant proteins) and obtain the most ideal recombinant proteins for vaccine design purposes.

新冠肺炎疫情是对世界各国科技和产业资源的严峻考验。面对缺乏针对该疾病的药理学策略,制定有效的SARS-CoV-2疫苗接种计划至关重要。由于缺乏生产手段和必要的基础设施,只有少数国家能够通过适当的生产、储存和分配方案充分应对这种病原体。这种疾病在许多国家,特别是在发展中国家已成为地方病,因此有必要根据这些国家的实际情况采取解决办法。在本文中,我们提出了一种利用生物信息学、免疫信息学和分子建模方法指导设计热稳定、通用、高效、安全的COVID-19候选疫苗,以针对SARS-CoV-2,选择具有较高免疫原性的抗原,并将其整合到M13噬菌体表面。我们的工作重点是利用噬菌体显示作为肽阵列来中和抗体(PdPANA)。这种替代方法在疫苗开发过程中可能有用,因为与现有方法相比,它可以提高生产的成本效益、耐久性和在不那么严格的热条件下分发疫苗的便利性。我们的研究结果表明,在SARS-CoV-2刺突蛋白(aa 344-583)的重度糖基化区,从其糖基化间区可以获得有用的抗原肽,用于M13噬菌体展示系统。PdPANA,我们提出的方法可能有助于克服噬菌体展示技术带来的经典缺点(即通过大量无用的重组蛋白文库进行体外筛选耗时),并获得最理想的重组蛋白用于疫苗设计。
{"title":"PdPANA: phagemid display as peptide array for neutralizing antibodies, an engineered <i>in silico</i> vaccine candidate against COVID-19.","authors":"Javier Uzcátegui, Khaleel Mullah, Daniel Buvat de Virgini, Andrés Mendoza, Rafael Urdaneta, Alejandra Naranjo","doi":"10.3389/fsysb.2024.1309891","DOIUrl":"10.3389/fsysb.2024.1309891","url":null,"abstract":"<p><p>The COVID-19 pandemic has tested the technical, scientific, and industrial resources of all countries worldwide. Faced with the absence of pharmacological strategies against the disease, an effective plan for vaccinating against SARS-CoV-2 has been essential. Due to the lack of production means and necessary infrastructure, only a few nations could adequately confront this pathogen with a production, storage, and distribution scheme in place. This disease has become endemic in many countries, especially in those that are developing, thus necessitating solutions tailored to their reality. In this paper, we propose an <i>in silico</i> method to guide the design towards a thermally stable, universal, efficient, and safe COVID-19 vaccine candidate against SARS-CoV-2 using bioinformatics, immunoinformatics, and molecular modeling approaches for the selection of antigens with higher immunogenic potential, incorporating them into the surface of the M13 phage. Our work focused on using phagemid display as peptide array for neutralizing antibodies (PdPANA). This alternative approach might be useful during the vaccine development process, since it could bring improvements in terms of cost-effectiveness in production, durability, and ease of distribution of the vaccine under less stringent thermal conditions compared to existing methods. Our results suggest that in the heavily glycosylated region of SARS-CoV-2 Spike protein (aa 344-583), from its inter-glycosylated regions, useful antigenic peptides can be obtained to be used in M13 phagemid display system. PdPANA, our proposed method might be useful to overcome the classic shortcoming posed by the phage-display technique (i.e., the time-consuming task of <i>in vitro</i> screening through great sized libraries with non-useful recombinant proteins) and obtain the most ideal recombinant proteins for vaccine design purposes.</p>","PeriodicalId":73109,"journal":{"name":"Frontiers in systems biology","volume":"4 ","pages":"1309891"},"PeriodicalIF":2.3,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12341989/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144849995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Building an Adverse Outcome Pathway network for COVID-19 为 COVID-19 建立不良后果途径网络
Pub Date : 2024-06-07 DOI: 10.3389/fsysb.2024.1384481
P. Nymark, Laure-Alix Clerbaux, Maria-João Amorim, Christos Andronis, Francesca de Bernardi, Gillina F. G. Bezemer, Sandra Coecke, Felicity N. E. Gavins, Daniel Jacobson, E. Lekka, Luigi Margiotta-Casaluci, Marvin Martens, S. Mayasich, Holly M. Mortensen, Young Jun Kim, M. Sachana, Shihori Tanabe, V. Virvilis, Steve W. Edwards, Sabina Halappanavar
The COVID-19 pandemic generated large amounts of data on the disease pathogenesis leading to a need for organizing the vast knowledge in a succinct manner. Between April 2020 and February 2023, the CIAO consortium exploited the Adverse Outcome Pathway (AOP) framework to comprehensively gather and systematically organize published scientific literature on COVID-19 pathology. The project considered 24 pathways relevant for COVID-19 by identifying essential key events (KEs) leading to 19 adverse outcomes observed in patients. While an individual AOP defines causally linked perturbed KEs towards an outcome, building an AOP network visually reflect the interrelatedness of the various pathways and outcomes. In this study, 17 of those COVID-19 AOPs were selected based on quality criteria to computationally derive an AOP network. This primary network highlighted the need to consider tissue specificity and helped to identify missing or redundant elements which were then manually implemented in the final network. Such a network enabled visualization of the complex interactions of the KEs leading to the various outcomes of the multifaceted COVID-19 and confirmed the central role of the inflammatory response in the disease. In addition, this study disclosed the importance of terminology harmonization and of tissue/organ specificity for network building. Furthermore the unequal completeness and quality of information contained in the AOPs highlighted the need for tighter implementation of the FAIR principles to improve AOP findability, accessibility, interoperability and re-usability. Finally, the study underlined that describing KEs specific to SARS-CoV-2 replication and discriminating physiological from pathological inflammation is necessary but requires adaptations to the framework. Hence, based on the challenges encountered, we proposed recommendations relevant for ongoing and future AOP-aligned consortia aiming to build computationally biologically meaningful AOP networks in the context of, but not limited to, viral diseases.
COVID-19 大流行产生了大量有关该疾病发病机制的数据,因此需要以简洁的方式整理大量知识。2020 年 4 月至 2023 年 2 月期间,CIAO 联盟利用不良后果途径(AOP)框架,全面收集和系统整理已发表的有关 COVID-19 病理学的科学文献。该项目通过确定导致在患者身上观察到的 19 种不良结果的基本关键事件 (KE),考虑了与 COVID-19 相关的 24 种途径。虽然单个 AOP 定义了导致结果的因果关系,但建立 AOP 网络可直观地反映出各种途径和结果之间的相互关联性。在本研究中,根据质量标准从 COVID-19 的 AOP 中选择了 17 个,通过计算得出了 AOP 网络。该初级网络强调了考虑组织特异性的必要性,并有助于识别缺失或冗余的元素,然后在最终网络中手动实现这些元素。这样一个网络使导致 COVID-19 多方面不同结果的关键基因之间复杂的相互作用可视化,并证实了炎症反应在疾病中的核心作用。此外,这项研究还揭示了术语统一和组织/器官特异性对网络构建的重要性。此外,AOP 中所含信息的完整性和质量参差不齐,这突出表明需要更严格地执行 FAIR 原则,以提高 AOP 的可查找性、可访问性、互操作性和可重用性。最后,研究强调,描述 SARS-CoV-2 复制的特定关键关键因子以及区分生理性和病理性炎症是必要的,但需要对框架进行调整。因此,基于所遇到的挑战,我们为正在进行的和未来的AOP联盟提出了相关建议,这些联盟的目标是在病毒性疾病(但不仅限于病毒性疾病)的背景下建立具有计算生物学意义的AOP网络。
{"title":"Building an Adverse Outcome Pathway network for COVID-19","authors":"P. Nymark, Laure-Alix Clerbaux, Maria-João Amorim, Christos Andronis, Francesca de Bernardi, Gillina F. G. Bezemer, Sandra Coecke, Felicity N. E. Gavins, Daniel Jacobson, E. Lekka, Luigi Margiotta-Casaluci, Marvin Martens, S. Mayasich, Holly M. Mortensen, Young Jun Kim, M. Sachana, Shihori Tanabe, V. Virvilis, Steve W. Edwards, Sabina Halappanavar","doi":"10.3389/fsysb.2024.1384481","DOIUrl":"https://doi.org/10.3389/fsysb.2024.1384481","url":null,"abstract":"The COVID-19 pandemic generated large amounts of data on the disease pathogenesis leading to a need for organizing the vast knowledge in a succinct manner. Between April 2020 and February 2023, the CIAO consortium exploited the Adverse Outcome Pathway (AOP) framework to comprehensively gather and systematically organize published scientific literature on COVID-19 pathology. The project considered 24 pathways relevant for COVID-19 by identifying essential key events (KEs) leading to 19 adverse outcomes observed in patients. While an individual AOP defines causally linked perturbed KEs towards an outcome, building an AOP network visually reflect the interrelatedness of the various pathways and outcomes. In this study, 17 of those COVID-19 AOPs were selected based on quality criteria to computationally derive an AOP network. This primary network highlighted the need to consider tissue specificity and helped to identify missing or redundant elements which were then manually implemented in the final network. Such a network enabled visualization of the complex interactions of the KEs leading to the various outcomes of the multifaceted COVID-19 and confirmed the central role of the inflammatory response in the disease. In addition, this study disclosed the importance of terminology harmonization and of tissue/organ specificity for network building. Furthermore the unequal completeness and quality of information contained in the AOPs highlighted the need for tighter implementation of the FAIR principles to improve AOP findability, accessibility, interoperability and re-usability. Finally, the study underlined that describing KEs specific to SARS-CoV-2 replication and discriminating physiological from pathological inflammation is necessary but requires adaptations to the framework. Hence, based on the challenges encountered, we proposed recommendations relevant for ongoing and future AOP-aligned consortia aiming to build computationally biologically meaningful AOP networks in the context of, but not limited to, viral diseases.","PeriodicalId":73109,"journal":{"name":"Frontiers in systems biology","volume":" 29","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141373398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
De novo prediction of functional effects of genetic variants from DNA sequences based on context-specific molecular information 基于特定上下文的分子信息,从 DNA 序列全新预测遗传变异的功能效应
Pub Date : 2024-06-03 DOI: 10.3389/fsysb.2024.1402664
Jiaxin Yang, Sikta Das Adhikari, Hao Wang, Binbin Huang, Wenjie Qi, Yuehua Cui, Jianrong Wang
Deciphering the functional effects of noncoding genetic variants stands as a fundamental challenge in human genetics. Traditional approaches, such as Genome-Wide Association Studies (GWAS), Transcriptome-Wide Association Studies (TWAS), and Quantitative Trait Loci (QTL) studies, are constrained by obscured the underlying molecular-level mechanisms, making it challenging to unravel the genetic basis of complex traits. The advent of Next-Generation Sequencing (NGS) technologies has enabled context-specific genome-wide measurements, encompassing gene expression, chromatin accessibility, epigenetic marks, and transcription factor binding sites, to be obtained across diverse cell types and tissues, paving the way for decoding genetic variation effects directly from DNA sequences only. The de novo predictions of functional effects are pivotal for enhancing our comprehension of transcriptional regulation and its disruptions caused by the plethora of noncoding genetic variants linked to human diseases and traits. This review provides a systematic overview of the state-of-the-art models and algorithms for genetic variant effect predictions, including traditional sequence-based models, Deep Learning models, and the cutting-edge Foundation Models. It delves into the ongoing challenges and prospective directions, presenting an in-depth perspective on contemporary developments in this domain.
破解非编码基因变异的功能效应是人类遗传学面临的一项基本挑战。传统的方法,如全基因组关联研究(GWAS)、全转录组关联研究(TWAS)和定量性状位点研究(QTL),受制于模糊的分子水平机制,使得揭示复杂性状的遗传基础具有挑战性。下一代测序(NGS)技术的出现使人们能够在不同的细胞类型和组织中获得特定的全基因组测量结果,包括基因表达、染色质可及性、表观遗传标记和转录因子结合位点,为仅从 DNA 序列直接解码遗传变异效应铺平了道路。对功能效应的全新预测,对于提高我们对转录调控及其由与人类疾病和性状相关的大量非编码基因变异引起的破坏的理解至关重要。本综述系统地概述了用于遗传变异效应预测的最先进模型和算法,包括传统的基于序列的模型、深度学习模型和最先进的基础模型。它深入探讨了当前面临的挑战和未来的发展方向,对该领域的当代发展提出了深入的看法。
{"title":"De novo prediction of functional effects of genetic variants from DNA sequences based on context-specific molecular information","authors":"Jiaxin Yang, Sikta Das Adhikari, Hao Wang, Binbin Huang, Wenjie Qi, Yuehua Cui, Jianrong Wang","doi":"10.3389/fsysb.2024.1402664","DOIUrl":"https://doi.org/10.3389/fsysb.2024.1402664","url":null,"abstract":"Deciphering the functional effects of noncoding genetic variants stands as a fundamental challenge in human genetics. Traditional approaches, such as Genome-Wide Association Studies (GWAS), Transcriptome-Wide Association Studies (TWAS), and Quantitative Trait Loci (QTL) studies, are constrained by obscured the underlying molecular-level mechanisms, making it challenging to unravel the genetic basis of complex traits. The advent of Next-Generation Sequencing (NGS) technologies has enabled context-specific genome-wide measurements, encompassing gene expression, chromatin accessibility, epigenetic marks, and transcription factor binding sites, to be obtained across diverse cell types and tissues, paving the way for decoding genetic variation effects directly from DNA sequences only. The de novo predictions of functional effects are pivotal for enhancing our comprehension of transcriptional regulation and its disruptions caused by the plethora of noncoding genetic variants linked to human diseases and traits. This review provides a systematic overview of the state-of-the-art models and algorithms for genetic variant effect predictions, including traditional sequence-based models, Deep Learning models, and the cutting-edge Foundation Models. It delves into the ongoing challenges and prospective directions, presenting an in-depth perspective on contemporary developments in this domain.","PeriodicalId":73109,"journal":{"name":"Frontiers in systems biology","volume":"28 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141272489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Surface-displayed silicatein-α enzyme in bioengineered E. coli enables biocementation and silica mineralization. 生物工程大肠杆菌表面显示的硅蛋白α酶能够实现生物胶结和硅矿化。
IF 2.3 Pub Date : 2024-05-30 eCollection Date: 2024-01-01 DOI: 10.3389/fsysb.2024.1377188
Toriana N Vigil, Nikolas K Schwendeman, Melanie L M Grogger, Victoria L Morrison, Margaret C Warner, Nathaniel B Bone, Morgan T Vance, David C Morris, Kristi McElmurry, Bryan W Berger, J Jordan Steel

Biocementation is an exciting biomanufacturing alternative to common cement, which is a significant contributor of CO2 greenhouse gas production. In nature biocementation processes are usually modulated via ureolytic microbes, such as Sporosarcina pasteurii, precipitating calcium carbonate to cement particles together, but these ureolytic reactions also produce ammonium and carbonate byproducts, which may have detrimental effects on the environment. As an alternative approach, this work examines biosilicification via surface-displayed silicatein-α in bio-engineered E. coli as an in vivo biocementation strategy. The surface-display of silicatein-α with ice nucleation protein is a novel protein fusion combination that effectively enables biosilicification, which is the polymerization of silica species in solution, from the surface of E. coli bacterial cells. Biosilicification with silicatein-α produces biocementation products with comparable compressive strength as S. pasteurii. This biosilicification approach takes advantage of the high silica content found naturally in sand and does not produce the ammonium and carbonate byproducts of ureolytic bacteria, making this a more environmentally friendly biocementation strategy.

生物水泥是一种令人兴奋的替代普通水泥的生物制造技术,而普通水泥是二氧化碳温室气体生产的重要贡献者。在自然界中,生物胶结过程通常是通过溶脲菌(如巴氏孢杆菌)将碳酸钙沉淀成胶结颗粒来调节的,但这些溶脲反应也会产生铵和碳酸盐副产物,这可能对环境产生有害影响。作为一种替代方法,本研究通过生物工程大肠杆菌中表面显示的硅酸盐蛋白-α来研究生物硅化,作为一种体内生物胶结策略。硅蛋白-α与冰核蛋白的表面显示是一种新型的蛋白质融合组合,可以有效地实现生物硅化,即从大肠杆菌细胞表面开始的溶液中二氧化硅的聚合。硅酸盐蛋白-α的生物硅化作用产生的生物胶结产物具有与巴氏杆菌相当的抗压强度。这种生物硅化方法利用了砂中天然硅含量高的优势,并且不会产生溶尿细菌的铵和碳酸盐副产物,使其成为一种更环保的生物胶结策略。
{"title":"Surface-displayed silicatein-α enzyme in bioengineered <i>E. coli</i> enables biocementation and silica mineralization.","authors":"Toriana N Vigil, Nikolas K Schwendeman, Melanie L M Grogger, Victoria L Morrison, Margaret C Warner, Nathaniel B Bone, Morgan T Vance, David C Morris, Kristi McElmurry, Bryan W Berger, J Jordan Steel","doi":"10.3389/fsysb.2024.1377188","DOIUrl":"10.3389/fsysb.2024.1377188","url":null,"abstract":"<p><p>Biocementation is an exciting biomanufacturing alternative to common cement, which is a significant contributor of CO<sub>2</sub> greenhouse gas production. In nature biocementation processes are usually modulated via ureolytic microbes, such as <i>Sporosarcina pasteurii,</i> precipitating calcium carbonate to cement particles together, but these ureolytic reactions also produce ammonium and carbonate byproducts, which may have detrimental effects on the environment. As an alternative approach, this work examines biosilicification via surface-displayed silicatein-α in bio-engineered <i>E. coli</i> as an <i>in vivo</i> biocementation strategy. The surface-display of silicatein-α with ice nucleation protein is a novel protein fusion combination that effectively enables biosilicification, which is the polymerization of silica species in solution, from the surface of <i>E. coli</i> bacterial cells. Biosilicification with silicatein-α produces biocementation products with comparable compressive strength as <i>S. pasteurii.</i> This biosilicification approach takes advantage of the high silica content found naturally in sand and does not produce the ammonium and carbonate byproducts of ureolytic bacteria, making this a more environmentally friendly biocementation strategy.</p>","PeriodicalId":73109,"journal":{"name":"Frontiers in systems biology","volume":"4 ","pages":"1377188"},"PeriodicalIF":2.3,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12341959/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144849998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Elucidating a genomic signature associated with behavioral and executive function after moderate to severe pediatric TBI: a systems biology informed approach 阐明与中重度儿科创伤后行为和执行功能相关的基因组特征:一种系统生物学方法
Pub Date : 2024-04-25 DOI: 10.3389/fsysb.2024.1293265
B. Kurowski, A. Treble-Barna, Valentina Pilipenko, Lisa J. Martin, Anil G. Jegga, Aimee E Miley, Nanhua Zhang, Anthony Fabio, Ranjit S. Chima, Anna-Lynne R. Adlam, Kenneth Kaufman, Michael J Bell, Sue R Beers, Stephen R. Wisniewski, Shari L. Wade
Introduction: There is significant unexplained variability in behavioral and executive functioning after pediatric traumatic brain injury (TBI). Prior research indicates that there are likely genetic contributions; however, current research is limited. The purpose of this study is to use a systems biology informed approach to characterize the genomic signature related to behavioral and executive functioning ∼12 months after moderate through severe TBI in children.Methods: Participants were from two prospective cohorts of children with severe TBI (Cohort #1) and moderate-severe TBI and an orthopedic injury (OI) group (Cohort #2). Participants included 196 children (n = 72 and n = 124 total from each respective cohort), ranging in age between 0–17 years at the time of injury. In total, 86 children had severe TBI, 49 had moderate TBI, and 61 had an OI. Global behavioral functioning assessed via the Child Behavior Checklist and executive function assessed via the Behavioral Rating Inventory of Executive Function at ∼ 12 months post injury served as outcomes. To test for a genomic signature, we compared the number of nominally significant (p < 0.05) polymorphisms associated with the outcomes in our systems biology identified genes to a set 10,000 permutations using control genes (e.g., not implicated by systems biology). We used the ToppFun application from Toppgene Suite to identify enriched biologic processes likely to be associated with behavioral and executive function outcomes.Results: At 12 months post injury, injury type (TBI vs OI) by polymorphism interaction was significantly enriched in systems biology selected genes for behavioral and executive function outcomes, suggesting these genes form a genomic signature. Effect sizes of the associations from our genes of interest ranged from .2–.5 for the top 5% of variants. Systems biology analysis of the variants associated with the top 5% effect sizes indicated enrichment in several specific biologic processes and systems.Discussion: Findings indicate that a genomic signature may explain heterogeneity of behavioral and executive outcomes after moderate and severe TBI. This work provides the foundation for constructing genomic signatures and integrating systems biology and genetic information into future recovery, prognostic, and treatment algorithms.
导言:小儿创伤性脑损伤(TBI)后的行为和执行功能存在很大的变异,原因不明。先前的研究表明,这可能与遗传因素有关;但目前的研究还很有限。本研究的目的是利用系统生物学方法来描述与儿童中度至重度创伤性脑损伤后 12 个月内的行为和执行功能相关的基因组特征:参与者来自两个前瞻性队列,分别是重度创伤性脑损伤儿童组(队列 1)和中度创伤性脑损伤及矫形损伤(OI)儿童组(队列 2)。参与者包括 196 名儿童(每个队列中分别有 72 名和 124 名儿童),受伤时年龄在 0-17 岁之间。其中,86 名儿童患有严重创伤性脑损伤,49 名儿童患有中度创伤性脑损伤,61 名儿童患有开放性损伤。通过儿童行为检查表评估总体行为功能,并在受伤后 12 个月内通过执行功能行为评级量表评估执行功能。为了测试基因组特征,我们比较了系统生物学鉴定基因中与结果相关的名义上有意义(p < 0.05)的多态性数量,以及使用对照基因(如系统生物学未涉及的基因)进行的10,000次排列组合。我们使用 Toppgene Suite 中的 ToppFun 应用程序来识别可能与行为和执行功能结果相关的富集生物过程:结果:在受伤后 12 个月,受伤类型(创伤性脑损伤与脑损伤)与多态性的交互作用在系统生物学选定的行为和执行功能结果基因中显著富集,表明这些基因形成了基因组特征。与我们感兴趣的基因相关的效应大小在前 5%的变异中介于 0.2-.5 之间。对与前 5%效应大小相关的变异进行的系统生物学分析表明,这些变异丰富了几个特定的生物过程和系统:讨论:研究结果表明,基因组特征可以解释中度和重度创伤性脑损伤后行为和执行结果的异质性。这项工作为构建基因组特征以及将系统生物学和遗传信息整合到未来的康复、预后和治疗算法中奠定了基础。
{"title":"Elucidating a genomic signature associated with behavioral and executive function after moderate to severe pediatric TBI: a systems biology informed approach","authors":"B. Kurowski, A. Treble-Barna, Valentina Pilipenko, Lisa J. Martin, Anil G. Jegga, Aimee E Miley, Nanhua Zhang, Anthony Fabio, Ranjit S. Chima, Anna-Lynne R. Adlam, Kenneth Kaufman, Michael J Bell, Sue R Beers, Stephen R. Wisniewski, Shari L. Wade","doi":"10.3389/fsysb.2024.1293265","DOIUrl":"https://doi.org/10.3389/fsysb.2024.1293265","url":null,"abstract":"Introduction: There is significant unexplained variability in behavioral and executive functioning after pediatric traumatic brain injury (TBI). Prior research indicates that there are likely genetic contributions; however, current research is limited. The purpose of this study is to use a systems biology informed approach to characterize the genomic signature related to behavioral and executive functioning ∼12 months after moderate through severe TBI in children.Methods: Participants were from two prospective cohorts of children with severe TBI (Cohort #1) and moderate-severe TBI and an orthopedic injury (OI) group (Cohort #2). Participants included 196 children (n = 72 and n = 124 total from each respective cohort), ranging in age between 0–17 years at the time of injury. In total, 86 children had severe TBI, 49 had moderate TBI, and 61 had an OI. Global behavioral functioning assessed via the Child Behavior Checklist and executive function assessed via the Behavioral Rating Inventory of Executive Function at ∼ 12 months post injury served as outcomes. To test for a genomic signature, we compared the number of nominally significant (p < 0.05) polymorphisms associated with the outcomes in our systems biology identified genes to a set 10,000 permutations using control genes (e.g., not implicated by systems biology). We used the ToppFun application from Toppgene Suite to identify enriched biologic processes likely to be associated with behavioral and executive function outcomes.Results: At 12 months post injury, injury type (TBI vs OI) by polymorphism interaction was significantly enriched in systems biology selected genes for behavioral and executive function outcomes, suggesting these genes form a genomic signature. Effect sizes of the associations from our genes of interest ranged from .2–.5 for the top 5% of variants. Systems biology analysis of the variants associated with the top 5% effect sizes indicated enrichment in several specific biologic processes and systems.Discussion: Findings indicate that a genomic signature may explain heterogeneity of behavioral and executive outcomes after moderate and severe TBI. This work provides the foundation for constructing genomic signatures and integrating systems biology and genetic information into future recovery, prognostic, and treatment algorithms.","PeriodicalId":73109,"journal":{"name":"Frontiers in systems biology","volume":"26 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140658194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Frontiers in systems biology
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1