首页 > 最新文献

Gene regulation and systems biology最新文献

英文 中文
Fractal topology of gene promoter networks at phase transitions. 基因启动子网络相变的分形拓扑结构。
Pub Date : 2010-07-28 DOI: 10.4137/grsb.s5389
Preston R Aldrich, Robert K Horsley, Yousuf A Ahmed, Joseph J Williamson, Stefan M Turcic

Much is known regarding the structure and logic of genetic regulatory networks. Less understood is the contextual organization of promoter signals used during transcription initiation, the most pivotal stage during gene expression. Here we show that promoter networks organize spontaneously at a dimension between the 1-dimension of the DNA and 3-dimension of the cell. Network methods were used to visualize the global structure of E. coli sigma (sigma) recognition footprints using published promoter sequences (RegulonDB). Footprints were rendered as networks with weighted edges representing bp-sharing between promoters (nodes). Serial thresholding revealed phase transitions at positions predicted by percolation theory, and nuclei denoting short steps through promoter space with geometrically constrained linkages. The network nuclei are fractals, a power-law organization not yet described for promoters. Genome-wide promoter abundance also scaled as a power-law. We propose a general model for the development of a fractal nucleus in a transcriptional grammar.

关于基因调控网络的结构和逻辑,我们知道的很多。转录起始是基因表达过程中最关键的阶段,人们对启动子信号的上下文组织知之甚少。在这里,我们表明启动子网络在DNA的一维和细胞的三维之间自发组织。利用已发表的启动子序列(RegulonDB),利用网络方法可视化大肠杆菌sigma (sigma)识别足迹的全局结构。足迹被渲染为带有加权边的网络,表示启动子(节点)之间的bp共享。序列阈值分析揭示了在渗流理论预测的位置上的相变,以及原子核在几何约束连接下通过启动子空间的短步。网络核是分形的,这是一种幂律组织,还没有被描述为启动子。全基因组启动子丰度也按幂律缩放。我们提出了一个通用模型的发展分形核在转录语法。
{"title":"Fractal topology of gene promoter networks at phase transitions.","authors":"Preston R Aldrich,&nbsp;Robert K Horsley,&nbsp;Yousuf A Ahmed,&nbsp;Joseph J Williamson,&nbsp;Stefan M Turcic","doi":"10.4137/grsb.s5389","DOIUrl":"https://doi.org/10.4137/grsb.s5389","url":null,"abstract":"<p><p>Much is known regarding the structure and logic of genetic regulatory networks. Less understood is the contextual organization of promoter signals used during transcription initiation, the most pivotal stage during gene expression. Here we show that promoter networks organize spontaneously at a dimension between the 1-dimension of the DNA and 3-dimension of the cell. Network methods were used to visualize the global structure of E. coli sigma (sigma) recognition footprints using published promoter sequences (RegulonDB). Footprints were rendered as networks with weighted edges representing bp-sharing between promoters (nodes). Serial thresholding revealed phase transitions at positions predicted by percolation theory, and nuclei denoting short steps through promoter space with geometrically constrained linkages. The network nuclei are fractals, a power-law organization not yet described for promoters. Genome-wide promoter abundance also scaled as a power-law. We propose a general model for the development of a fractal nucleus in a transcriptional grammar.</p>","PeriodicalId":73138,"journal":{"name":"Gene regulation and systems biology","volume":"4 ","pages":"75-82"},"PeriodicalIF":0.0,"publicationDate":"2010-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/grsb.s5389","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29182943","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: 12
Do DNA microarrays tell the story of gene expression? DNA微阵列能讲述基因表达的故事吗?
Pub Date : 2010-06-29 DOI: 10.4137/grsb.s4657
Simon Rosenfeld

Poor reproducibility of microarray measurements is a major obstacle to their application as an instrument for clinical diagnostics. In this paper, several aspects of poor reproducibility are analyzed. All of them belong to the category of interpretive weaknesses of DNA microarray technology. First, the attention is drawn to the fact that absence of the information regarding post-transcriptional mRNA stability makes it impossible to evaluate the level of gene activity from the relative mRNA abundances, the quantities available from microarray measurements. Second, irreducible intracellular variability with persistent patterns of stochasticity and burstiness put natural limits to reproducibility. Third, strong interactions within intracellular biomolecular networks make it highly problematic to build a bridge between transcription rates of individual genes and structural fidelity of their genetic codes. For these reasons, the microarray measurements of relative mRNA abundances are more appropriate in laboratory settings as a tool for scientific research, hypotheses generating and producing the leads for subsequent validation through more sophisticated technologies. As to clinical settings, where firm conclusive diagnoses, not the leads for further experimentation, are required, microarrays still have a long way to go until they become a reliable instrument in patient-related decision making.

微阵列测量的可重复性差是其作为临床诊断仪器应用的主要障碍。本文对再现性差的几个方面进行了分析。这些都属于DNA微阵列技术的解释弱点范畴。首先,需要注意的是,由于缺乏关于转录后mRNA稳定性的信息,因此不可能从相对mRNA丰度(从微阵列测量可获得的数量)来评估基因活性水平。其次,不可还原的细胞内变异性与持续的随机性和突发性模式自然限制了可重复性。第三,细胞内生物分子网络之间的强烈相互作用使得在单个基因的转录率与其遗传密码的结构保真度之间建立桥梁变得非常困难。由于这些原因,相对mRNA丰度的微阵列测量更适合在实验室环境中作为科学研究的工具,通过更复杂的技术产生假设和产生后续验证的线索。至于临床环境,需要的是确凿的结论性诊断,而不是进一步实验的线索,微阵列在成为患者相关决策的可靠工具之前还有很长的路要走。
{"title":"Do DNA microarrays tell the story of gene expression?","authors":"Simon Rosenfeld","doi":"10.4137/grsb.s4657","DOIUrl":"https://doi.org/10.4137/grsb.s4657","url":null,"abstract":"<p><p>Poor reproducibility of microarray measurements is a major obstacle to their application as an instrument for clinical diagnostics. In this paper, several aspects of poor reproducibility are analyzed. All of them belong to the category of interpretive weaknesses of DNA microarray technology. First, the attention is drawn to the fact that absence of the information regarding post-transcriptional mRNA stability makes it impossible to evaluate the level of gene activity from the relative mRNA abundances, the quantities available from microarray measurements. Second, irreducible intracellular variability with persistent patterns of stochasticity and burstiness put natural limits to reproducibility. Third, strong interactions within intracellular biomolecular networks make it highly problematic to build a bridge between transcription rates of individual genes and structural fidelity of their genetic codes. For these reasons, the microarray measurements of relative mRNA abundances are more appropriate in laboratory settings as a tool for scientific research, hypotheses generating and producing the leads for subsequent validation through more sophisticated technologies. As to clinical settings, where firm conclusive diagnoses, not the leads for further experimentation, are required, microarrays still have a long way to go until they become a reliable instrument in patient-related decision making.</p>","PeriodicalId":73138,"journal":{"name":"Gene regulation and systems biology","volume":"4 ","pages":"61-73"},"PeriodicalIF":0.0,"publicationDate":"2010-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/grsb.s4657","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29119145","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: 13
Model-Based Analysis of FGF23 Regulation in Chronic Kidney Disease. 慢性肾脏疾病中FGF23调控的模型分析
Pub Date : 2010-06-09 DOI: 10.4137/grsb.s4880
Hiroki Yokota, Ana Pires, João F Raposo, Hugo G Ferreira

The mechanism of FGF23 action in calcium/phosphorus metabolism of patients with chronic kidney disease (CKD) was studied using a mathematical model and clinical data in a public domain. We have previously built a physiological model that describes interactions of PTH, calcitriol, and FGF23 in mineral metabolism encompassing organs such as bone, intestine, kidney, and parathyroid glands. Since an elevated FGF23 level in serum is a characteristic symptom of CKD patients, we evaluate herein potential metabolic alterations in response to administration of a neutralizing antibody against FGF23. Using the parameters identified from available clinical data, we observed that a transient decrease in the FGF23 level elevated the serum concentrations of PTH, calcitriol, and phosphorus. The model also predicted that the administration reduced a urinary output of phosphorous. This model-based prediction indicated that the therapeutic reduction of FGF23 by the neutralizing antibody did not reduce phosphorus burden of CKD patients and decreased the urinary phosphorous excretion. Thus, the high FGF23 level in CKD patients was predicted to be a failure of FGF23-mediated phosphorous excretion. The results herein indicate that it is necessary to understand the mechanism in CKD in which the level of FGF23 is elevated without effectively regulating phosphorus.

利用数学模型和公开的临床数据研究了FGF23在慢性肾脏疾病(CKD)患者钙/磷代谢中的作用机制。我们之前已经建立了一个生理模型,描述了PTH、骨化三醇和FGF23在包括骨、肠、肾和甲状旁腺等器官的矿物质代谢中的相互作用。由于血清中FGF23水平升高是CKD患者的特征性症状,我们在此评估了FGF23中和抗体治疗后潜在的代谢改变。利用从现有临床数据中确定的参数,我们观察到FGF23水平的短暂下降会升高甲状旁腺激素、骨化三醇和磷的血清浓度。该模型还预测,给药减少了尿中磷的排泄量。这一基于模型的预测表明,中和抗体治疗性降低FGF23并没有减少CKD患者的磷负担,也没有减少尿磷排泄。因此,CKD患者的高FGF23水平被预测为FGF23介导的磷排泄失败。本研究结果提示,有必要了解CKD中FGF23水平升高而没有有效调节磷的机制。
{"title":"Model-Based Analysis of FGF23 Regulation in Chronic Kidney Disease.","authors":"Hiroki Yokota,&nbsp;Ana Pires,&nbsp;João F Raposo,&nbsp;Hugo G Ferreira","doi":"10.4137/grsb.s4880","DOIUrl":"https://doi.org/10.4137/grsb.s4880","url":null,"abstract":"<p><p>The mechanism of FGF23 action in calcium/phosphorus metabolism of patients with chronic kidney disease (CKD) was studied using a mathematical model and clinical data in a public domain. We have previously built a physiological model that describes interactions of PTH, calcitriol, and FGF23 in mineral metabolism encompassing organs such as bone, intestine, kidney, and parathyroid glands. Since an elevated FGF23 level in serum is a characteristic symptom of CKD patients, we evaluate herein potential metabolic alterations in response to administration of a neutralizing antibody against FGF23. Using the parameters identified from available clinical data, we observed that a transient decrease in the FGF23 level elevated the serum concentrations of PTH, calcitriol, and phosphorus. The model also predicted that the administration reduced a urinary output of phosphorous. This model-based prediction indicated that the therapeutic reduction of FGF23 by the neutralizing antibody did not reduce phosphorus burden of CKD patients and decreased the urinary phosphorous excretion. Thus, the high FGF23 level in CKD patients was predicted to be a failure of FGF23-mediated phosphorous excretion. The results herein indicate that it is necessary to understand the mechanism in CKD in which the level of FGF23 is elevated without effectively regulating phosphorus.</p>","PeriodicalId":73138,"journal":{"name":"Gene regulation and systems biology","volume":"4 ","pages":"53-60"},"PeriodicalIF":0.0,"publicationDate":"2010-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/grsb.s4880","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29119146","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: 4
GA-based Design Algorithms for the Robust Synthetic Genetic Oscillators with Prescribed Amplitude, Period and Phase. 基于遗传算法的定幅、定周期、定相位鲁棒合成遗传振荡器设计算法。
Pub Date : 2010-05-24 DOI: 10.4137/grsb.s4818
Bor-Sen Chen, Po-Wei Chen

In the past decade, the development of synthetic gene networks has attracted much attention from many researchers. In particular, the genetic oscillator known as the repressilator has become a paradigm for how to design a gene network with a desired dynamic behaviour. Even though the repressilator can show oscillatory properties in its protein concentrations, their amplitudes, frequencies and phases are perturbed by the kinetic parametric fluctuations (intrinsic molecular perturbations) and external disturbances (extrinsic molecular noises) of the environment. Therefore, how to design a robust genetic oscillator with desired amplitude, frequency and phase under stochastic intrinsic and extrinsic molecular noises is an important topic for synthetic biology.In this study, based on periodic reference signals with arbitrary amplitudes, frequencies and phases, a robust synthetic gene oscillator is designed by tuning the kinetic parameters of repressilator via a genetic algorithm (GA) so that the protein concentrations can track the desired periodic reference signals under intrinsic and extrinsic molecular noises. GA is a stochastic optimization algorithm which was inspired by the mechanisms of natural selection and evolution genetics. By the proposed GA-based design algorithm, the repressilator can track the desired amplitude, frequency and phase of oscillation under intrinsic and extrinsic noises through the optimization of fitness function.The proposed GA-based design algorithm can mimic the natural selection in evolutionary process to select adequate kinetic parameters for robust genetic oscillators. The design method can be easily extended to any synthetic gene network design with prescribed behaviours.

在过去的十年中,合成基因网络的发展受到了许多研究者的关注。特别是,基因振荡器被称为再压子已经成为一个范例,如何设计一个基因网络与期望的动态行为。尽管再压剂可以在其蛋白质浓度中显示振荡特性,但它们的振幅、频率和相位受到环境的动力学参数波动(内在分子扰动)和外部干扰(外在分子噪声)的干扰。因此,如何在随机分子内外噪声条件下设计具有理想振幅、频率和相位的鲁棒遗传振荡器是合成生物学研究的重要课题。本研究以任意振幅、频率和相位的周期参考信号为基础,通过遗传算法调整调控器的动力学参数,设计了一个鲁棒的合成基因振荡器,使蛋白质浓度在内源和外源分子噪声下都能跟踪所需的周期参考信号。遗传算法是一种受自然选择和进化遗传学机制启发的随机优化算法。通过对适应度函数的优化,在所提出的基于遗传算法的设计算法中,稳压器能够在内外噪声条件下跟踪期望的振荡幅度、频率和相位。提出的基于遗传算法的设计算法可以模拟进化过程中的自然选择,为鲁棒遗传振子选择合适的动力学参数。该设计方法可以很容易地扩展到任何具有规定行为的合成基因网络设计。
{"title":"GA-based Design Algorithms for the Robust Synthetic Genetic Oscillators with Prescribed Amplitude, Period and Phase.","authors":"Bor-Sen Chen,&nbsp;Po-Wei Chen","doi":"10.4137/grsb.s4818","DOIUrl":"https://doi.org/10.4137/grsb.s4818","url":null,"abstract":"<p><p>In the past decade, the development of synthetic gene networks has attracted much attention from many researchers. In particular, the genetic oscillator known as the repressilator has become a paradigm for how to design a gene network with a desired dynamic behaviour. Even though the repressilator can show oscillatory properties in its protein concentrations, their amplitudes, frequencies and phases are perturbed by the kinetic parametric fluctuations (intrinsic molecular perturbations) and external disturbances (extrinsic molecular noises) of the environment. Therefore, how to design a robust genetic oscillator with desired amplitude, frequency and phase under stochastic intrinsic and extrinsic molecular noises is an important topic for synthetic biology.In this study, based on periodic reference signals with arbitrary amplitudes, frequencies and phases, a robust synthetic gene oscillator is designed by tuning the kinetic parameters of repressilator via a genetic algorithm (GA) so that the protein concentrations can track the desired periodic reference signals under intrinsic and extrinsic molecular noises. GA is a stochastic optimization algorithm which was inspired by the mechanisms of natural selection and evolution genetics. By the proposed GA-based design algorithm, the repressilator can track the desired amplitude, frequency and phase of oscillation under intrinsic and extrinsic noises through the optimization of fitness function.The proposed GA-based design algorithm can mimic the natural selection in evolutionary process to select adequate kinetic parameters for robust genetic oscillators. The design method can be easily extended to any synthetic gene network design with prescribed behaviours.</p>","PeriodicalId":73138,"journal":{"name":"Gene regulation and systems biology","volume":"4 ","pages":"35-52"},"PeriodicalIF":0.0,"publicationDate":"2010-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/grsb.s4818","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29043752","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: 28
Transcriptional response of E. coli upon FimH-mediated fimbrial adhesion. 大肠杆菌对fimh介导的毛粘附的转录反应。
Pub Date : 2010-03-24 DOI: 10.4137/grsb.s4525
Prasanna Bhomkar, Wayne Materi, Valentyna Semenchenko, David S Wishart

Functionalities which may be genetically programmed into a bacterium are limited by its range of possible activities and its sensory capabilities. Therefore, enhancing the bacterial sensory repertoire is a crucial step for expanded utility in potential biomedical, industrial or environmental applications. Using microarray and qRT-PCR analyses, we have investigated transcription in E. coli (strain CSH50) following FimH-mediated adhesion to biocompatible substrates. Specifically, wild-type FimH-mediated adhesion of E. coli to mannose agarose beads and His-tagged FimH-mediated adhesion to Ni(2+)-NTA beads both led to induction of ahpCF, dps, grxA and marRAB genes among bound cells relative to unbound cells. The strongly-induced genes are known to be regulated by OxyR or SoxS cytoplasmic redox sensors. Some differentially altered genes also overlapped with those implicated in biofilm formation. This study provides an insight into transcriptional events following FimH-mediated adhesion and may provide a platform for elucidation of the signaling circuit necessary for engineering a synthetic attachment response in E. coli.

基因赋予细菌的功能受到细菌活动范围和感官能力的限制。因此,增强细菌的感觉库是扩大潜在生物医学、工业或环境应用的关键一步。利用芯片和qRT-PCR分析,我们研究了大肠杆菌(菌株CSH50)在fimh介导的粘附到生物相容性底物后的转录。具体而言,野生型fimh介导的大肠杆菌对甘露糖琼脂糖珠的粘附和his标记的fimh介导的Ni(2+)-NTA珠的粘附都导致结合细胞相对于未结合细胞诱导ahpCF、dps、grxA和marRAB基因。已知强诱导基因受OxyR或SoxS细胞质氧化还原传感器的调控。一些差异改变的基因也与那些涉及生物膜形成的基因重叠。该研究提供了对fimh介导的粘附后转录事件的深入了解,并可能为阐明大肠杆菌中工程合成附着反应所需的信号通路提供平台。
{"title":"Transcriptional response of E. coli upon FimH-mediated fimbrial adhesion.","authors":"Prasanna Bhomkar,&nbsp;Wayne Materi,&nbsp;Valentyna Semenchenko,&nbsp;David S Wishart","doi":"10.4137/grsb.s4525","DOIUrl":"https://doi.org/10.4137/grsb.s4525","url":null,"abstract":"<p><p>Functionalities which may be genetically programmed into a bacterium are limited by its range of possible activities and its sensory capabilities. Therefore, enhancing the bacterial sensory repertoire is a crucial step for expanded utility in potential biomedical, industrial or environmental applications. Using microarray and qRT-PCR analyses, we have investigated transcription in E. coli (strain CSH50) following FimH-mediated adhesion to biocompatible substrates. Specifically, wild-type FimH-mediated adhesion of E. coli to mannose agarose beads and His-tagged FimH-mediated adhesion to Ni(2+)-NTA beads both led to induction of ahpCF, dps, grxA and marRAB genes among bound cells relative to unbound cells. The strongly-induced genes are known to be regulated by OxyR or SoxS cytoplasmic redox sensors. Some differentially altered genes also overlapped with those implicated in biofilm formation. This study provides an insight into transcriptional events following FimH-mediated adhesion and may provide a platform for elucidation of the signaling circuit necessary for engineering a synthetic attachment response in E. coli.</p>","PeriodicalId":73138,"journal":{"name":"Gene regulation and systems biology","volume":"4 ","pages":"1-17"},"PeriodicalIF":0.0,"publicationDate":"2010-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/grsb.s4525","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28979415","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: 63
Inference of cancer-specific gene regulatory networks using soft computing rules. 利用软计算规则推断癌症特异性基因调控网络。
Pub Date : 2010-03-24 DOI: 10.4137/grsb.s4509
Xiaosheng Wang, Osamu Gotoh

Perturbations of gene regulatory networks are essentially responsible for oncogenesis. Therefore, inferring the gene regulatory networks is a key step to overcoming cancer. In this work, we propose a method for inferring directed gene regulatory networks based on soft computing rules, which can identify important cause-effect regulatory relations of gene expression. First, we identify important genes associated with a specific cancer (colon cancer) using a supervised learning approach. Next, we reconstruct the gene regulatory networks by inferring the regulatory relations among the identified genes, and their regulated relations by other genes within the genome. We obtain two meaningful findings. One is that upregulated genes are regulated by more genes than downregulated ones, while downregulated genes regulate more genes than upregulated ones. The other one is that tumor suppressors suppress tumor activators and activate other tumor suppressors strongly, while tumor activators activate other tumor activators and suppress tumor suppressors weakly, indicating the robustness of biological systems. These findings provide valuable insights into the pathogenesis of cancer.

基因调控网络的扰动是肿瘤发生的主要原因。因此,推断基因调控网络是攻克癌症的关键一步。在这项工作中,我们提出了一种基于软计算规则推断定向基因调控网络的方法,该方法可以识别基因表达的重要因果调控关系。首先,我们使用监督学习方法识别与特定癌症(结肠癌)相关的重要基因。接下来,我们通过推断已鉴定基因之间的调控关系,以及基因组内其他基因对它们的调控关系,重构基因调控网络。我们得到了两个有意义的发现。一是上调基因比下调基因受更多基因调控,而下调基因比上调基因受更多基因调控。二是肿瘤抑制因子对肿瘤激活因子的抑制作用较强,对其他肿瘤抑制因子的激活作用较强,而肿瘤激活因子对其他肿瘤激活因子的激活作用较弱,说明生物系统具有鲁棒性。这些发现为癌症的发病机制提供了有价值的见解。
{"title":"Inference of cancer-specific gene regulatory networks using soft computing rules.","authors":"Xiaosheng Wang,&nbsp;Osamu Gotoh","doi":"10.4137/grsb.s4509","DOIUrl":"https://doi.org/10.4137/grsb.s4509","url":null,"abstract":"<p><p>Perturbations of gene regulatory networks are essentially responsible for oncogenesis. Therefore, inferring the gene regulatory networks is a key step to overcoming cancer. In this work, we propose a method for inferring directed gene regulatory networks based on soft computing rules, which can identify important cause-effect regulatory relations of gene expression. First, we identify important genes associated with a specific cancer (colon cancer) using a supervised learning approach. Next, we reconstruct the gene regulatory networks by inferring the regulatory relations among the identified genes, and their regulated relations by other genes within the genome. We obtain two meaningful findings. One is that upregulated genes are regulated by more genes than downregulated ones, while downregulated genes regulate more genes than upregulated ones. The other one is that tumor suppressors suppress tumor activators and activate other tumor suppressors strongly, while tumor activators activate other tumor activators and suppress tumor suppressors weakly, indicating the robustness of biological systems. These findings provide valuable insights into the pathogenesis of cancer.</p>","PeriodicalId":73138,"journal":{"name":"Gene regulation and systems biology","volume":"4 ","pages":"19-34"},"PeriodicalIF":0.0,"publicationDate":"2010-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/grsb.s4509","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28979416","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: 16
Microarray data analysis of gene expression evolution. 基因表达进化的微阵列数据分析。
Pub Date : 2009-11-27 DOI: 10.4137/grsb.s2997
Honghuang Lin

Microarrays are becoming a widely used tool to study gene expression evolution. A recent paper by Wang and Rekaya describes a comprehensive study of gene expression evolution by microarray. The work provides a perspective to study gene expression evolution in terms of functional enrichment and promoter conservation. It was found that gene expression patterns are highly conserved in some biological processes, but the correlation between promoter and gene expression is insignificant. This scope of this work and future improvement to study gene expression evolution will be discussed in this article.

微阵列正在成为研究基因表达进化的一种广泛使用的工具。Wang和Rekaya最近发表的一篇论文描述了通过微阵列对基因表达进化的全面研究。这为从功能富集和启动子保护的角度研究基因表达进化提供了新的视角。研究发现,基因表达模式在某些生物学过程中具有高度保守性,但启动子与基因表达的相关性不显著。本文将讨论这项工作的范围和未来基因表达进化研究的改进。
{"title":"Microarray data analysis of gene expression evolution.","authors":"Honghuang Lin","doi":"10.4137/grsb.s2997","DOIUrl":"https://doi.org/10.4137/grsb.s2997","url":null,"abstract":"<p><p>Microarrays are becoming a widely used tool to study gene expression evolution. A recent paper by Wang and Rekaya describes a comprehensive study of gene expression evolution by microarray. The work provides a perspective to study gene expression evolution in terms of functional enrichment and promoter conservation. It was found that gene expression patterns are highly conserved in some biological processes, but the correlation between promoter and gene expression is insignificant. This scope of this work and future improvement to study gene expression evolution will be discussed in this article.</p>","PeriodicalId":73138,"journal":{"name":"Gene regulation and systems biology","volume":"3 ","pages":"211-4"},"PeriodicalIF":0.0,"publicationDate":"2009-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/grsb.s2997","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28631417","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
Hereditary Inclusion Body Myopathy (HIBM2). 遗传性包涵体肌病(HIBM2)。
Pub Date : 2009-10-21 DOI: 10.4137/grsb.s2594
Chris M Jay, Nick Levonyak, Gregory Nemunaitis, Phillip B Maples, John Nemunaitis

Hereditary inclusion body myopathy type 2 (HIBM2) is a myopathy characterized by progressive muscle weakness with early adult onset. The disease is the result of a recessive mutation in the Glucosamine (UDP-N-acetyl)-2-epimerase/N-acetylmannosamine kinase gene (GNE), which results in reduced enzyme function and sialic acid levels. A majority of individuals with HIBM2 are from Iranian-Jewish or Japanese decent, but isolated cases have been identified world wide. This article reviews the diagnostic criteria for HIBM2. Current research with a highlight on the biology of the disease and the role of GNE in the sialic acid pathway are assessed. Finally, therapeutic investigations and animal models are discussed with a focus on future studies to better understand the pathology of Hereditary Inclusion Body Myopathy and move therapeutic agents towards clinical trials.

遗传性包涵体肌病2型(HIBM2)是一种以进行性肌肉无力为特征的肌病,成人早期发病。该疾病是葡萄糖胺(udp - n -乙酰)-2- epimase / n -乙酰氨基甘露胺激酶基因(GNE)隐性突变的结果,导致酶功能和唾液酸水平降低。大多数HIBM2患者来自伊朗-犹太人或日本血统,但在世界范围内也发现了孤立病例。本文综述了HIBM2的诊断标准。目前的研究重点是疾病的生物学和GNE在唾液酸途径中的作用。最后,讨论了治疗研究和动物模型,重点讨论了未来的研究,以更好地了解遗传性包涵体肌病的病理,并将治疗药物推向临床试验。
{"title":"Hereditary Inclusion Body Myopathy (HIBM2).","authors":"Chris M Jay,&nbsp;Nick Levonyak,&nbsp;Gregory Nemunaitis,&nbsp;Phillip B Maples,&nbsp;John Nemunaitis","doi":"10.4137/grsb.s2594","DOIUrl":"https://doi.org/10.4137/grsb.s2594","url":null,"abstract":"<p><p>Hereditary inclusion body myopathy type 2 (HIBM2) is a myopathy characterized by progressive muscle weakness with early adult onset. The disease is the result of a recessive mutation in the Glucosamine (UDP-N-acetyl)-2-epimerase/N-acetylmannosamine kinase gene (GNE), which results in reduced enzyme function and sialic acid levels. A majority of individuals with HIBM2 are from Iranian-Jewish or Japanese decent, but isolated cases have been identified world wide. This article reviews the diagnostic criteria for HIBM2. Current research with a highlight on the biology of the disease and the role of GNE in the sialic acid pathway are assessed. Finally, therapeutic investigations and animal models are discussed with a focus on future studies to better understand the pathology of Hereditary Inclusion Body Myopathy and move therapeutic agents towards clinical trials.</p>","PeriodicalId":73138,"journal":{"name":"Gene regulation and systems biology","volume":"3 ","pages":"181-90"},"PeriodicalIF":0.0,"publicationDate":"2009-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/grsb.s2594","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28631420","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: 13
Stochastic spatio-temporal dynamic model for gene/protein interaction network in early Drosophila development. 果蝇早期发育过程中基因/蛋白相互作用网络的随机时空动态模型。
Pub Date : 2009-10-19
Cheng-Wei Li, Bor-Sen Chen

In order to investigate the possible mechanisms for eve stripe formation of Drosophila embryo, a spatio-temporal gene/protein interaction network model is proposed to mimic dynamic behaviors of protein synthesis, protein decay, mRNA decay, protein diffusion, transcription regulations and autoregulation to analyze the interplay of genes and proteins at different compartments in early embryogenesis. In this study, we use the maximum likelihood (ML) method to identify the stochastic 3-D Embryo Space-Time (3-DEST) dynamic model for gene/protein interaction network via 3-D mRNA and protein expression data and then use the Akaike Information Criterion (AIC) to prune the gene/protein interaction network. The identified gene/protein interaction network allows us not only to analyze the dynamic interplay of genes and proteins on the border of eve stripes but also to infer that eve stripes are established and maintained by network motifs built by the cooperation between transcription regulations and diffusion mechanisms in early embryogenesis. Literature reference with the wet experiments of gene mutations provides a clue for validating the identified network. The proposed spatio-temporal dynamic model can be extended to gene/protein network construction of different biological phenotypes, which depend on compartments, e.g. postnatal stem/progenitor cell differentiation.

为了探讨果蝇胚胎中均匀条纹形成的可能机制,本文建立了一个时空基因/蛋白质相互作用网络模型,模拟了果蝇胚胎中蛋白质合成、蛋白质衰变、mRNA衰变、蛋白质扩散、转录调控和自调节等动态行为,分析了果蝇胚胎早期不同区室中基因和蛋白质的相互作用。本研究利用最大似然(ML)方法,通过三维mRNA和蛋白质表达数据,识别基因/蛋白质相互作用网络的随机三维胚胎时空(3-DEST)动态模型,并利用赤池信息准则(AIC)对基因/蛋白质相互作用网络进行剪接。基因/蛋白相互作用网络的发现不仅使我们能够分析均匀条纹边缘基因和蛋白质的动态相互作用,而且还可以推断均匀条纹是由早期胚胎发生中转录调控和扩散机制共同构建的网络基序建立和维持的。文献参考和基因突变湿实验为验证所识别的网络提供了线索。所提出的时空动态模型可以扩展到不同生物表型的基因/蛋白网络构建,这些表型依赖于室室,例如出生后干细胞/祖细胞分化。
{"title":"Stochastic spatio-temporal dynamic model for gene/protein interaction network in early Drosophila development.","authors":"Cheng-Wei Li,&nbsp;Bor-Sen Chen","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>In order to investigate the possible mechanisms for eve stripe formation of Drosophila embryo, a spatio-temporal gene/protein interaction network model is proposed to mimic dynamic behaviors of protein synthesis, protein decay, mRNA decay, protein diffusion, transcription regulations and autoregulation to analyze the interplay of genes and proteins at different compartments in early embryogenesis. In this study, we use the maximum likelihood (ML) method to identify the stochastic 3-D Embryo Space-Time (3-DEST) dynamic model for gene/protein interaction network via 3-D mRNA and protein expression data and then use the Akaike Information Criterion (AIC) to prune the gene/protein interaction network. The identified gene/protein interaction network allows us not only to analyze the dynamic interplay of genes and proteins on the border of eve stripes but also to infer that eve stripes are established and maintained by network motifs built by the cooperation between transcription regulations and diffusion mechanisms in early embryogenesis. Literature reference with the wet experiments of gene mutations provides a clue for validating the identified network. The proposed spatio-temporal dynamic model can be extended to gene/protein network construction of different biological phenotypes, which depend on compartments, e.g. postnatal stem/progenitor cell differentiation.</p>","PeriodicalId":73138,"journal":{"name":"Gene regulation and systems biology","volume":"3 ","pages":"191-210"},"PeriodicalIF":0.0,"publicationDate":"2009-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2796968/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28631416","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
Characteristics of transcriptional activity in nonlinear dynamics of genetic regulatory networks. 遗传调控网络非线性动力学中的转录活性特征。
Pub Date : 2009-10-19 DOI: 10.4137/grsb.s3119
Simon Rosenfeld

Microarray measurements of mRNA abundances is a standard tool for evaluation of transcriptional activity in functional genomics. The methodology underlying these measurements assumes existence of a direct link between transcription levels, that is, gene-specific mRNA copy numbers present in the cell, and transcription rates, that is, the numbers of gene-specific mRNA molecules synthesized per unit of time. In this paper, the question of whether or not such a tight interdependence may exist is examined in the context of nonlinear dynamics of genetic regulatory networks. Using the equations of chemical kinetics, a model has been constructed that is capable of explicitly taking into consideration nonlinear interactions between the genes through the teamwork of transcription factors. Jacobian analysis of stability has shown that steady state equilibrium is impossible in such systems. However, phase space compressibility is found to be negative, thus suggesting that asymptotic stability may exist and assume either the form of limit cycle or of a chaotic attractor. It is argued that in rapidly fluctuating or chaotic systems, direct evaluation of transcription rates through transcription levels is highly problematic. It is also noted that even if a hypothetical steady state did exist, the knowledge of transcription levels alone would not be sufficient for the evaluation of transcription rates; an additional set of parameters, namely the mRNA decay rates, would be required. An overall conclusion of the work is that the measurements of mRNA abundances are not truly representative of the functionality of genes and structural fidelity of the genetic codes.

微阵列测量mRNA丰度是功能基因组学中评估转录活性的标准工具。这些测量的基础方法假设在转录水平(即细胞中存在的基因特异性mRNA拷贝数)和转录率(即单位时间内合成的基因特异性mRNA分子数)之间存在直接联系。在本文中,是否存在这种紧密的相互依存关系的问题是在遗传调控网络的非线性动力学背景下进行检查。利用化学动力学方程,构建了一个模型,该模型能够通过转录因子的团队合作明确考虑基因之间的非线性相互作用。稳定性的雅可比分析表明,在这种系统中稳态平衡是不可能的。然而,发现相空间压缩率为负,从而表明可能存在渐近稳定性,并以极限环或混沌吸引子的形式存在。有人认为,在快速波动或混沌系统中,通过转录水平直接评估转录率是非常有问题的。还需要指出的是,即使假设的稳定状态确实存在,单靠转录水平的知识也不足以评估转录率;还需要一组额外的参数,即mRNA的衰减率。这项工作的总体结论是,mRNA丰度的测量并不能真正代表基因的功能和遗传密码的结构保真度。
{"title":"Characteristics of transcriptional activity in nonlinear dynamics of genetic regulatory networks.","authors":"Simon Rosenfeld","doi":"10.4137/grsb.s3119","DOIUrl":"https://doi.org/10.4137/grsb.s3119","url":null,"abstract":"<p><p>Microarray measurements of mRNA abundances is a standard tool for evaluation of transcriptional activity in functional genomics. The methodology underlying these measurements assumes existence of a direct link between transcription levels, that is, gene-specific mRNA copy numbers present in the cell, and transcription rates, that is, the numbers of gene-specific mRNA molecules synthesized per unit of time. In this paper, the question of whether or not such a tight interdependence may exist is examined in the context of nonlinear dynamics of genetic regulatory networks. Using the equations of chemical kinetics, a model has been constructed that is capable of explicitly taking into consideration nonlinear interactions between the genes through the teamwork of transcription factors. Jacobian analysis of stability has shown that steady state equilibrium is impossible in such systems. However, phase space compressibility is found to be negative, thus suggesting that asymptotic stability may exist and assume either the form of limit cycle or of a chaotic attractor. It is argued that in rapidly fluctuating or chaotic systems, direct evaluation of transcription rates through transcription levels is highly problematic. It is also noted that even if a hypothetical steady state did exist, the knowledge of transcription levels alone would not be sufficient for the evaluation of transcription rates; an additional set of parameters, namely the mRNA decay rates, would be required. An overall conclusion of the work is that the measurements of mRNA abundances are not truly representative of the functionality of genes and structural fidelity of the genetic codes.</p>","PeriodicalId":73138,"journal":{"name":"Gene regulation and systems biology","volume":"3 ","pages":"159-79"},"PeriodicalIF":0.0,"publicationDate":"2009-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/grsb.s3119","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28631419","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: 9
期刊
Gene regulation and 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:481959085
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