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2011 IEEE International Conference on Systems Biology (ISB)最新文献

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Parallel-META: A high-performance computational pipeline for metagenomic data analysis Parallel-META:用于宏基因组数据分析的高性能计算管道
Pub Date : 2011-10-03 DOI: 10.1109/ISB.2011.6033151
Xiaoquan Su, Jian Xu, K. Ning
Metagenomics method directly sequences and analyzes genome information from microbial communities. There are usually more than hundreds of genomes from different microbial species in the same community, and the main computational tasks for metagenomics data analysis include taxonomical and functional component of these genomes in the microbial community. Metagenomic data analysis is both data- and computation- intensive, which requires extensive computational power. Most of the current metagenomic data analysis softwares were designed to be used on a single computer, which could not match with the fast increasing number of large metagenomic projects' computational requirements. Therefore, advanced computational methods and pipelines have to be developed to cope with such need for efficient analyses. In this paper, we proposed Parallel-META, a GPU- and multi-core-CPU-based open-source pipeline for metagenomic data analysis, which enabled the efficient and parallel analysis of multiple metagenomic datasets. In Parallel-META, the similarity-based database search was parallelized based on GPU computing and multi-core CPU computing optimization. Experiments have shown that Parallel-META has at least 15 times speed-up compared to traditional metagenomic data analysis method, with the same accuracy of the results (http://www.bioenergychina.org:8800/).
宏基因组学方法直接对微生物群落的基因组信息进行测序和分析。在同一群落中,通常有数百个不同微生物物种的基因组,宏基因组学数据分析的主要计算任务包括微生物群落中这些基因组的分类和功能成分。宏基因组数据分析是数据密集型和计算密集型的,需要大量的计算能力。目前大多数宏基因组数据分析软件都设计为在单台计算机上使用,无法满足快速增长的大型宏基因组项目的计算需求。因此,必须开发先进的计算方法和管道来应对这种高效分析的需求。本文提出了一种基于GPU和多核cpu的开源宏基因组数据分析管道parallel - meta,实现了对多个宏基因组数据集的高效并行分析。在Parallel-META中,基于相似度的数据库搜索在GPU计算和多核CPU计算优化的基础上并行化。实验表明,Parallel-META与传统宏基因组数据分析方法相比,速度至少提高了15倍,结果精度相同(http://www.bioenergychina.org:8800/)。
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引用次数: 9
Intrinsic noise induced state transition in coupled positive and negative feedback genetic circuit 正负反馈耦合遗传电路中固有噪声诱导的状态跃迁
Pub Date : 2011-10-03 DOI: 10.1109/ISB.2011.6033178
Pei Wang, Jinhu Lu, Yuhuan Zhang, M. Ogorzałek
It is well known that gene regulatory circuits can be modeled by the deterministic or stochastic approach. In this paper, a three-component coupled positive and negative feedback genetic circuit is firstly modeled deterministically by Hill kinetics. Then, a corresponding stochastic model is also investigated by using Gellispie's stochastic simulation. Some typical dynamical behaviors of the genetic circuit are further discussed based on the bifurcation analysis of deterministic system, including monostability, bistability, excitability, and oscillation. This paper aims to further investigate the effect of intrinsic noise inherently in stochastic models on steady states transition. It includes: i) For the parameters in deterministically bistable region, intrinsic noise may induce bistable switch for the not too large system volume, which can be observed by the generation of a new stable steady state; ii) For the parameters in deterministically excitable region, intrinsic noise may induce periodic switch for the very large system volume, which can be observed by the stabilization of another unstable steady state and the switching between two stable states; iii) When time delays are introduced in these two models, similar phenomena can be observed. The above results will certainly increase the understanding of the inner relationships between different modeling for the genetic circuit. It sheds some light on the real- world engineering applications, such as the engineering design of synthetic circuits.
众所周知,基因调控回路可以通过确定性或随机方法来建模。本文首次用希尔动力学方法建立了三分量正负反馈耦合遗传回路的确定性模型。然后,利用Gellispie随机模拟方法研究了相应的随机模型。在对确定性系统进行分岔分析的基础上,进一步讨论了遗传电路的典型动力学行为,包括单稳定、双稳定、可激性和振荡。本文旨在进一步研究随机模型中固有噪声对稳态转换的影响。它包括:i)对于确定性双稳态区域内的参数,在系统体积不太大的情况下,本然噪声可能诱发双稳态切换,这可以通过产生新的稳定稳态来观察;ii)对于确定性可激发区的参数,在系统体积非常大的情况下,固有噪声会引起周期切换,这种切换可以通过另一个不稳定稳态的稳定化和两个稳定状态之间的切换来观察;iii)当这两个模型中引入时滞时,可以观察到类似的现象。上述结果必将加深对遗传电路不同模型之间内在关系的认识。它对现实世界的工程应用,如合成电路的工程设计有一定的启示。
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引用次数: 6
Inferring domain-domain interactions using an extended parsimony model 使用扩展简约模型推断域与域之间的相互作用
Pub Date : 2011-10-03 DOI: 10.1109/ISB.2011.6033181
Cheng Chen, Junfei Zhao, Qiang Huang, Rui-Sheng Wang, Xiang-Sun Zhang
High-throughput technologies have produced a large number of protein-protein interactions (PPIs) for different species. As protein domains are functional and structural units of proteins, many computational efforts have been made to identify domain-domain interactions (DDIs) from PPIs. Parsimony assumption is widely used in computational biology as the evolution of the nature is considered as a continuous optimization process. In the context of identifying DDIs, parsimony methods try to find a minimal set of DDIs that can explain the observed PPIs. This category of methods are promising since they can be formulated and solved easily. Besides, researches have shown that they could detect specific DDIs, which is often hard for many probabilistic methods. In this paper, we revisit the parsimony model by presenting two important extensions. First, ‘complex networks’ as an emerging concept is incorporated as prior knowledge into the parsimony model. With this improvement, the prediction accuracy increases, which to some extent enhances the biological meaning of the common property of complex networks. Second, two randomization tests are designed to show the parsimony nature of the DDIs in mediating PPIs, which corroborates the model validation.
高通量技术已经为不同的物种产生了大量的蛋白质-蛋白质相互作用(PPIs)。由于蛋白质结构域是蛋白质的功能和结构单元,许多计算工作已被用于从PPIs中识别域-域相互作用(ddi)。简约假设在计算生物学中被广泛应用,因为自然界的进化被认为是一个连续的优化过程。在确定ddi的背景下,简约方法试图找到一个最小的ddi集,可以解释观察到的ppi。这类方法很有前途,因为它们易于制定和求解。此外,研究表明,它们可以检测到特定的ddi,这是许多概率方法难以做到的。在本文中,我们通过提出两个重要的扩展来重新审视简约模型。首先,“复杂网络”作为一个新兴概念被作为先验知识纳入简约模型。这种改进提高了预测精度,在一定程度上增强了复杂网络共性的生物学意义。其次,设计了两个随机化测试来显示ddi在中介ppi中的简约性,这证实了模型验证。
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引用次数: 1
Parallel metabolomics of urine and serum revealed systematic alteration associated with renal disease 尿液和血清的平行代谢组学显示与肾脏疾病相关的系统性改变
Pub Date : 2011-10-03 DOI: 10.1109/ISB.2011.6033173
Xianfu Gao, Wanjia Chen, Rongxia Li, Minfeng Wang, Chunlei Chen, R. Zeng, Yueyi Deng
Background: Membranous nephropathy is an important glomerular disease characterized by podocyte injury and proteinuria, but no metabolomics research was reported as yet. Here, we performed a parallel metabolomics study, based on human urine and serum, to comprehensively profile systematic metabolic alterations, identify differential metabolites, and understand the pathogenic mechanism of membranous nephropathy. Results: There were obvious metabolic distinctions between the membranous nephropathy patients with urine protein lower than 3.5 g/24h (LUPM) and those higher than 3.5 g/24h (HUPM) by PLS-DA model analysis. In total, 26 urine metabolites and 9 serum metabolites were identified to account for such differences, and the majority of metabolites was significantly increased in HUPM patients whether for urines or for serums. Combining the results of urine with serum, all differential metabolites were classified to 5 classes. This classification helps globally insight the systematic metabolic alteration before and after blood flowing through kidney. Citric acid and 4 amino acids were markedly increased only in the serum samples of HUPM patients, implying more impaired filtration function of kidneys of HUPM patients than LUPM patients. The dicarboxylic acids, phenolic acids, and cholesterol were significantly elevated only in urines of HUPM patients, suggesting more severe oxidative attacks than LUPM patients. Conclusion: Parallel metabolomics of urine and serum revealed the systematic metabolic variations associated with LUPM and HUPM patients, where HUPM patients suffered more severe injury of kidney function and oxidative stresses than LUPM patients. This research exhibited a promising application of parallel metabolomics in renal diseases.
背景:膜性肾病是一种重要的肾小球疾病,以足细胞损伤和蛋白尿为特征,但尚未有代谢组学研究报道。在这里,我们进行了一项平行代谢组学研究,基于人类尿液和血清,以全面描述系统代谢改变,识别差异代谢物,并了解膜性肾病的致病机制。结果:PLS-DA模型分析尿蛋白低于3.5 g/24h (LUPM)与高于3.5 g/24h (HUPM)的膜性肾病患者代谢差异明显。总共鉴定出26种尿液代谢物和9种血清代谢物来解释这种差异,无论是尿液代谢物还是血清代谢物,HUPM患者的大多数代谢物都显着增加。结合尿液和血清结果,将所有差异代谢物分为5类。这种分类有助于全面了解血液流经肾脏前后的系统代谢变化。柠檬酸和4种氨基酸仅在HUPM患者血清样本中显著升高,表明HUPM患者肾脏滤过功能受损程度高于LUPM患者。双羧酸、酚酸和胆固醇仅在HUPM患者尿液中显著升高,提示氧化攻击比LUPM患者更严重。结论:尿液和血清平行代谢组学揭示了与LUPM和HUPM患者相关的系统性代谢变化,其中HUPM患者的肾功能损伤和氧化应激比LUPM患者更严重。本研究显示平行代谢组学在肾脏疾病中的应用前景广阔。
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引用次数: 0
Extrinsic vs. intrinsic noises in phage lambda genetic switch 噬菌体λ基因开关的外在与内在噪声
Pub Date : 2011-10-03 DOI: 10.1109/ISB.2011.6033122
Wei Tian, Hongyuan Zhu, X. Lei, P. Ao
Noises in biological modeling may be classified into two kinds: intrinsic noise, which derives from the variability in dominant molecular interaction and is responsible for the given phenomenon, and extrinsic noise, which arises from other sources, like fluctuations in the environment and so on. Phage lambda is a simple model organism that exhibits important noisy characteristics. It lives in either lysogenic state or lytic state after infecting a bacterium, that is determined by a genetic switch. The mathematical modeling of this genetic switch typically only considers intrinsic noise, though a previous study by one of present authors suggested the critical role of extrinsic noise. In the present study by comparing theoretical results of phage lambda in lysogeny with experiment data, we first achieve good numerical agreements of five constrains of phage lambda for averaged variables. This success indicates that current dominant molecular agents are right. In addition, we confirm the existence of extrinsic noise in lambda genetic switch and find it surprisingly large. This finding calls for an extension of the current mathematical model to better describe the noises. We also point out some possible sources of extrinsic noise.
生物建模中的噪声可分为两类:固有噪声,它来自于显性分子相互作用的可变性,是造成给定现象的原因;外在噪声,它来自于其他来源,如环境的波动等。噬菌体是一种简单的模式生物,具有重要的噪声特征。在感染细菌后,它要么活在溶原状态,要么活在溶原状态,这是由基因开关决定的。这种遗传开关的数学模型通常只考虑了内在噪声,尽管一位作者之前的研究表明了外在噪声的关键作用。本研究通过对噬菌体λ在溶原过程中的理论结果与实验数据的比较,首先得到了噬菌体λ对平均变量的5个约束的较好的数值一致性。这一成功表明目前占主导地位的分子制剂是正确的。此外,我们还证实了lambda遗传开关中存在外源噪声,并且发现其噪声大得惊人。这一发现要求对当前的数学模型进行扩展,以更好地描述噪声。我们还指出了一些可能的外部噪声来源。
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引用次数: 3
Floral structure and pollination in relation to fruit set in cynanchum otophyllum schneid 石竹的花结构和授粉与坐果的关系
Pub Date : 2011-10-03 DOI: 10.1109/ISB.2011.6033152
Ding-Kang Wang, Shu-Hua Zhai, Bin Wang, Guifen Sun
We studied the floral morphology and floral biology of Cynanchum otophyllum Schneid in experimental plots and field sites. Some observations were augmented by laboratory studies of floral traits, including scanning electron microscopy and light microscopy. The flower was characterized by a staminal corona. The pollinia were lodged in sacs on each side of the stigma and needed pollen vector for fruit production. C. otophyllum has characteristics similar to bee-pollinated plants. Honeybees (Apis cerana Fabricius) were the main pollinators. Pollinaria removal and pollinia insertion rates were low at 5.4% and 0.45%, respectively. The fruit set was only 2.2% in natural population. The flowering span of C. otophyllum was about 3 months, and the functional longevity of individual flowers was 6–8 days. The extended period may be related to the relatively low levels of effective pollinator activity. The flowers were self-incompatible. Umbels displayed open flowers for 9–10 days, and there was a large overlap in flowering time within and among inflorescences in a single plant. Therefore, a high level of self-pollination is possible. From the significant increases in fruit set in cross-pollinated flowers (12.6%) compared with self-pollinated flowers (1.52%), the low fruit set in C. otophyllum could be partially explained by pollen limitation.
本文在试验田和田间对金秋花的花形态和花生物学进行了研究。通过扫描电子显微镜和光学显微镜对花的性状进行了进一步的研究。这花的特点是有雄蕊花冠。花粉寄存于柱头两侧的囊中,需要花粉载体进行果实生产。C. otophyum具有与蜜蜂授粉植物相似的特征。蜜蜂(Apis cerana Fabricius)是主要授粉者。除粉率和插粉率较低,分别为5.4%和0.45%。在自然群体中坐果率仅为2.2%。花期约为3个月,单花功能寿命为6 ~ 8天。较长的时间可能与有效传粉者活动水平相对较低有关。这些花互不相容。伞形花序的开放期为9 ~ 10天,单株花序内和花序间的开花时间有较大的重叠。因此,高水平的自花授粉是可能的。异花结实率(12.6%)显著高于自花结实率(1.52%),表明花粉限制可能是其结实率低的部分原因。
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引用次数: 1
Systematic reconstruction of splicing regulatory modules by integrating many RNA-seq datasets 通过整合多个RNA-seq数据集系统地重建剪接调控模块
Pub Date : 2011-10-03 DOI: 10.1109/ISB.2011.6033164
Chao Dai, Wenyuan Li, Juan Liu, X. Zhou
Alternative splicing is a ubiquitous gene regulatory mechanism that dramatically increases the complexity of the proteome. In this paper we study splicing module, which we define as a set of cassette exons co-regulated by the same splicing factors. We have designed a tensor-based approach to identify co-splicing clusters that appear frequently across multiple conditions, thus very likely to represent splicing modules - a unit in the splicing regulatory network. In particular, we model each RNA-seq dataset as a co-splicing network, where the nodes represent exons and the edges are weighted by the correlations between exon inclusion rate profiles. We apply our tensor-based method to the 19 co-splicing networks derived from RNA-seq datasets and identify an atlas of frequent co-splicing clusters. We demonstrate that these identified clusters represent splicing modules by validating against four biological knowledge databases. The likelihood that a frequent co-splicing cluster is biologically meaningful increases with its recurrence across multiple datasets, highlighting the importance of the integrative approach. We also demonstrate that the co-splicing clusters reveal novel functional groups which cannot be identified by co-expression clusters, and that the same exons can dynamically participate in different pathways depending on different conditions and different other exons that are co-spliced.
选择性剪接是一种普遍存在的基因调控机制,它极大地增加了蛋白质组的复杂性。本文研究了剪接模块,我们将其定义为由相同剪接因子共同调控的一组盒式外显子。我们设计了一种基于张量的方法来识别在多种条件下频繁出现的共剪接簇,因此很可能代表剪接模块-剪接调节网络中的一个单元。特别是,我们将每个RNA-seq数据集建模为一个共剪接网络,其中节点代表外显子,边缘由外显子包含率谱之间的相关性加权。我们将基于张量的方法应用于来自RNA-seq数据集的19个共剪接网络,并确定了频繁共剪接簇的图谱。通过对四个生物知识数据库的验证,我们证明了这些识别的集群代表了拼接模块。频繁的共剪接簇具有生物学意义的可能性随着其在多个数据集上的重复而增加,这突出了整合方法的重要性。我们还证明了共剪接簇揭示了无法通过共表达簇识别的新功能群,并且相同的外显子可以根据不同的条件和不同的其他共剪接外显子动态参与不同的途径。
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引用次数: 0
RNADAP—RNA-Seq data annotation pipeline RNADAP-RNA-Seq数据标注管道
Pub Date : 2011-10-03 DOI: 10.1109/ISB.2011.6033125
Zunming Liu, Jingfa Xiao, Jiayan Wu, Jun Yu
RNA-Seq has become one of the most important new approaches for gene expression analysis as well as transcriptome analysis. The issue of how to analysis RNA-Seq data is one of the biggest challenges for current transcriptomics research. In this study, we develop an RNA-Seq data annotation pipeline named RNADAP, which is an efficient transcriptomes analysis tool to evaluate gene expression quantization in isoform level and compatible for reads data from different platforms. RNADAP is a typical Java application so the pipeline could be carried out on Windows as well as Linux. The installation process is convenient and user can grasp it very easily with a friendly user interface. RNADAP is a free, open-source software and written in Java. All source code, instructions, testing data and additional scripts are available at http://rnadap.sourceforge.net/.
RNA-Seq已成为基因表达分析和转录组分析最重要的新方法之一。如何分析RNA-Seq数据是当前转录组学研究面临的最大挑战之一。在本研究中,我们开发了一个名为RNADAP的RNA-Seq数据注释管道,该管道是一种高效的转录组分析工具,可在异构体水平上评估基因表达量化,并兼容不同平台的reads数据。RNADAP是一个典型的Java应用程序,因此管道既可以在Windows上执行,也可以在Linux上执行。安装过程方便,用户可以很容易地掌握它与友好的用户界面。RNADAP是一个免费的开源软件,用Java编写。所有源代码、说明、测试数据和附加脚本可在http://rnadap.sourceforge.net/上获得。
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引用次数: 0
Synchronization feature of coupled cell-cycle oscillators 耦合细胞周期振荡器的同步特性
Pub Date : 2011-10-03 DOI: 10.1109/ISB.2011.6033154
Wei Zhang, Xiufen Zou
Based on the model of the Xenopus embryonic cell cycle proposed in literature [1], which can exhibit sustained limit cycle oscillations, we first build a multi-cell system of these oscillators that are coupled through a common complex protein that plays an important role in the core regulation of cell-cycle oscillators, and then show synchronization features in this coupled multi-cell system. Through bifurcation analysis and numerical simulations, we give synchronization intervals of the sensitive parameters in the individual oscillator and the coupling parameters in the coupled oscillators. Then, we analyze the effects of these parameters on synchronization time, period and amplitude, and find interesting phenomena, e.g., there are two synchronization intervals of activation coefficient in the Hill function of the activated CDK1 that activates the Plk1, and different synchronization intervals have distinct influences on synchronization time, period and amplitude. More interestingly, we find that the coupled system can switch between a stable state and a stable periodic orbit. These results suggest that the reaction process that the activated cyclin-CDK1 activates the Plk1 has very important influence on the synchronization ability of the coupled system. Our work not only can be viewed as an important step toward the comprehensive understanding for mechanisms of Xenopus embryonic cell cycle and but also can provide the guide for further biological experiments.
基于文献[1]中提出的能够出现持续极限环振荡的非洲爪蟾胚胎细胞周期模型,我们首先构建了这些振荡因子通过一个共同的复杂蛋白偶联的多细胞系统,该蛋白在细胞周期振荡因子的核心调控中起重要作用,然后在这个偶联的多细胞系统中表现出同步特征。通过分岔分析和数值模拟,给出了单个振子中敏感参数的同步间隔和耦合振子中耦合参数的同步间隔。然后,我们分析了这些参数对同步时间、周期和幅度的影响,发现了有趣的现象,如活化CDK1激活Plk1的Hill函数中存在两个激活系数的同步间隔,不同的同步间隔对同步时间、周期和幅度的影响不同。更有趣的是,我们发现耦合系统可以在稳定状态和稳定周期轨道之间切换。这些结果表明,活化的cyclin-CDK1激活Plk1的反应过程对耦合系统的同步能力有非常重要的影响。本研究不仅为全面认识非洲爪蟾胚胎细胞周期机制迈出了重要的一步,而且可以为进一步的生物学实验提供指导。
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引用次数: 2
NRProF: Neural response based protein function prediction algorithm NRProF:基于神经反应的蛋白质功能预测算法
Pub Date : 2011-10-03 DOI: 10.1109/ISB.2011.6033117
H. Yalamanchili, Junwen Wang, Quan-Wu Xiao
A large amount of proteomic data is being generated due to the advancements in high-throughput genome sequencing. But the rate of functional annotation of these sequences falls far behind. To fill the gap between the number of sequences and their annotations, fast and accurate automated annotation methods are required. Many methods, such as GOblet, GOfigure, and Gotcha, are designed based on the BLAST search. Unfortunately, the sequence coverage of these methods is low as they cannot detect the remote homologues. The lack of annotation coverage of the existing methods advocates novel methods to improve protein function prediction. Here we present a automated protein functional assignment method based on the neural response algorithm, which simulates the neuronal behavior of the visual cortex in the human brain. The main idea of this algorithm is to define a distance metric that corresponds to the similarity of the subsequences and reflects how the human brain can distinguish different sequences. Given query protein, we predict the most similar target protein using a two layered neural response algorithm and thereby assigned the GO term of the target protein to the query. Our method predicted and ranked the actual leaf GO term among the top 5 probable GO terms with 87.66% accuracy. Results of the 5-fold cross validation and the comparison with PFP and FFPred servers indicate the prominent performance by our method. The NRProF program, the dataset, and help files are available at http://www.jjwanglab.org/NRProF/.
由于高通量基因组测序的进步,大量的蛋白质组学数据正在产生。但这些序列的功能注释率远远落后。为了填补序列数量与其标注之间的空白,需要快速、准确的自动标注方法。许多方法,如GOblet、GOfigure和Gotcha,都是基于BLAST搜索而设计的。不幸的是,这些方法的序列覆盖率较低,因为它们不能检测到远程同源物。现有方法缺乏注释覆盖,需要新的方法来改进蛋白质功能预测。本文提出了一种基于神经响应算法的蛋白质功能自动分配方法,该方法模拟了人脑视觉皮层的神经元行为。该算法的主要思想是定义一个距离度量,该距离度量对应于子序列的相似性,并反映人脑如何区分不同的序列。给定查询蛋白,我们使用两层神经响应算法预测最相似的目标蛋白,从而将目标蛋白的GO项分配给查询。我们的方法预测并将实际的叶子GO项排在前5个可能的GO项中,准确率为87.66%。5重交叉验证的结果以及与PFP和FFPred服务器的比较表明,我们的方法具有突出的性能。NRProF程序、数据集和帮助文件可在http://www.jjwanglab.org/NRProF/上获得。
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引用次数: 3
期刊
2011 IEEE International Conference on Systems Biology (ISB)
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