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2011 IEEE International Conference on Bioinformatics and Biomedicine Workshops (BIBMW)最新文献

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Coupling Oriented Hidden Markov Random Field Model with Local Clustering for Segmenting Blood Vessels and Measuring Spatial Structures in Images of Tumor Microenvironment 面向耦合的局部聚类隐马尔可夫随机场模型用于肿瘤微环境图像血管分割和空间结构测量
Yanqiao Zhu, Fuhai Li, D. Cridebring, Jinwen Ma, Stephen T. C. Wong, T. Vadakkan, Mei Zhang, John D. Landua, Wei Wei, M. Dickinson, J. Rosen, M. Lewis
Interactions between cancer cells and factors within the tumor microenvironment (mE) are essential for understanding tumor development. The spatial relationships between blood vessel cells and cancer cells, e.g. tumor initiating cells (TICs), are an important parameter. Accurate segmentation of blood vessel is necessary for the quantization of their spatial relationships. However, this remains an open problem due to uneven intensity and low signal to noise ratio (SNR). To overcome these challenges, we propose a novel approach that integrates an oriented hidden Markov random field model (Ori-HMRF) with local clustering. The local clustering delineates boundaries of blood vessel segments with low SNR. Then blood vessel segments are viewed as random variables in the Ori-HMRF and their spatial dependence is defined based on directional information. The Ori-HMRF model suppresses noise and generates accurate blood vessel segmentation results. Experimental validations were conducted on both normal mammary and breast cancer tissues.
癌细胞与肿瘤微环境(mE)内因子之间的相互作用对于理解肿瘤的发展至关重要。血管细胞和癌细胞(如肿瘤起始细胞)之间的空间关系是一个重要的参数。血管的精确分割是量化血管空间关系的必要条件。然而,由于强度不均和低信噪比(SNR),这仍然是一个悬而未决的问题。为了克服这些挑战,我们提出了一种将面向隐马尔可夫随机场模型(Ori-HMRF)与局部聚类相结合的新方法。局部聚类描述低信噪比的血管段边界。然后将血管段视为Ori-HMRF中的随机变量,并根据方向信息定义其空间依赖性。Ori-HMRF模型抑制了噪声,产生了准确的血管分割结果。在正常乳腺组织和乳腺癌组织中均进行了实验验证。
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引用次数: 8
Assessments of intra- and inter-host diversity of hepatitis C virus using Next Generation Sequencing and Mass spectrometry 使用下一代测序和质谱法评估丙型肝炎病毒宿主内和宿主间的多样性
Zoya Dimitrova, David S. Campo, S. Ramachandran, Gilberto Vaughan, L. Ganova-Raeva, Yulin Lin, J. Forbi, G. Xia, P. Skums, B. Pearlman, Y. Khudyakov
Recent advances in sequencing methods allow the analysis of an unprecedented number of viral variants from infected patients and present a novel opportunity for understanding viral evolution, drug resistance and immune escape. In the present paper, we compared three technologies for amplicon analysis: (i) Next Generation Sequencing; (ii) Clonal sequencing using End-point Limiting-dilution for isolation of individual sequence variants followed by Real-Time PCR and sequencing; and (iii) Mass spectrometry of base-specific cleavage reactions of a target sequence. Hypervariable region 1 of hepatitis C virus was analyzed using these three technologies to assess diversity and genetic relatedness of intra-host viral populations in specimens obtained from 38 patients. Estimates of population heterogeneity varied among technologies. However, all three technologies were equally accurate in identification of genetic relatedness among viral strains, supporting their application in molecular epidemiology for tracking viral variants and detecting transmission events.
测序方法的最新进展允许分析来自感染患者的空前数量的病毒变体,并为了解病毒进化,耐药性和免疫逃逸提供了新的机会。在本文中,我们比较了三种扩增子分析技术:(i)下一代测序;(ii)克隆测序,使用终点限制稀释法分离单个序列变异,然后进行实时荧光定量PCR和测序;(iii)目标序列碱基特异性裂解反应的质谱分析。使用这三种技术分析了38例患者标本中丙型肝炎病毒的高变区1,以评估宿主内病毒种群的多样性和遗传相关性。对人口异质性的估计因技术而异。然而,这三种技术在鉴定病毒株之间的遗传相关性方面同样准确,支持它们在分子流行病学中用于跟踪病毒变异和检测传播事件的应用。
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引用次数: 3
Rapid identification of multi-PTMs peptide sequence tags with a graph search approach 基于图搜索方法的多ptms肽序列标签快速识别
Hui Li, Chunmei Liu, M. Rwebangira, L. Burge, W. Southerland
Identifying post-translational modifications (PTMs) is a big challenge for proteomics. Mass spectrometry is a popular tool for the identification of peptide sequence. Here we present a method for rapid identification of PTMs by mass spectrometry based on graph theory. The approach takes advantage of several possibility pair's values of corresponding Tandem Mass Spectrometry (MS/MS), and uses score function to screen candidate peptide sequences. We proposed the Pair Peak of Set (PPS) and used the most possibility mass of PPS as the root of graph tree, the rest ones are viewed as the reference node of graph. Our experiment on 2620 experimental MS/MS with two PTMs shows that our approach achieves better accuracy than PepNovo approaches with higher efficiency and it could deal with low quality PTMs data.
鉴定翻译后修饰(PTMs)是蛋白质组学的一大挑战。质谱法是一种常用的肽序列鉴定工具。本文提出了一种基于图论的质谱法快速鉴定ptm的方法。该方法利用串联质谱(MS/MS)对应的几个可能对值,利用分数函数筛选候选肽序列。我们提出了集合的对峰(PPS),并将PPS的最大可能质量作为图树的根,其余的作为图树的参考节点。在2620实验MS/MS上进行的实验表明,该方法比PepNovo方法精度更高,效率更高,可以处理低质量的PTMs数据。
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引用次数: 0
A symmetry-driven BP algorithm for the Discretizable Molecular Distance Geometry Problem 可离散分子距离几何问题的对称驱动BP算法
A. Mucherino, C. Lavor, Leo Liberti
Branch & Prune (BP) is a deterministic algorithm for the solution of the Discretizable Molecular Distance Geometry Problem (DMDGP). This problem has important applications in the field of structural biology, in particular for the determination of the three-dimensional conformation of a molecule by using information obtained by NMR techniques. In recent works, we proved that the search domain of the DMDGP, which is represented by a binary tree, contains various symmetries which are related to the number of solutions to the problem. In the present work, we propose a variant of the BP algorithm which is able to exploit the information regarding the symmetries to speed up the search. Computational experiments show that the symmetry-driven BP (symBP) outperforms the original BP algorithm in particular when instances having several solutions are considered.
BP (Branch & Prune)是求解可离散分子距离几何问题(DMDGP)的确定性算法。这个问题在结构生物学领域有重要的应用,特别是在利用核磁共振技术获得的信息来确定分子的三维构象方面。在最近的工作中,我们证明了用二叉树表示的DMDGP的搜索域包含各种对称性,这些对称性与问题的解的数量有关。在目前的工作中,我们提出了一种BP算法的变体,该算法能够利用有关对称性的信息来加快搜索速度。计算实验表明,对称驱动BP (symBP)算法在考虑多个解的情况下优于原BP算法。
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引用次数: 9
imiRTP: An Integrated Method to Identifying miRNA-target Interactions in Arabidopsis thaliana imiRTP:一种鉴定拟南芥mirna -靶标相互作用的综合方法
Jiandong Ding, Shusi Yu, U. Ohler, J. Guan, Shuigeng Zhou
MiRNA are about 22nt long small noncoding RNAs that post transcription ally regulate gene expression in animals, plants and protozoa. Confident identification of MiRNA-Target Interactions (MTI) is vital to understand their function. Currently, several integrated programs and databases are available for animal miRNAs, the mechanisms of which are significantly different from plant miRNAs. Here we present imiRTP, an integrated MTI prediction and analysis toolkit for Arabidopsis thaliana. It features two important functions: (i) combination of several effective plant miRNA target prediction methods provides a sufficiently large MTI candidate set, and (ii) different filters allow for an efficient selection of potential targets. The modularity of imiRTP enables the prediction of high quality targets on genome-wide scale.
MiRNA是一种长约22nt的非编码小rna,在动物、植物和原生动物中起转录后调控基因表达的作用。确定MiRNA-Target相互作用(MTI)对了解其功能至关重要。目前,针对动物mirna的集成程序和数据库比较多,但动物mirna的机制与植物mirna有很大的不同。在这里,我们提出了imiRTP,一个集成的拟南芥MTI预测和分析工具包。它具有两个重要功能:(i)几种有效的植物miRNA靶标预测方法的组合提供了足够大的MTI候选集,(ii)不同的过滤器允许有效地选择潜在靶标。imiRTP的模块化使其能够在全基因组范围内预测高质量靶点。
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引用次数: 6
Integration of polygenic and individual SNP effects in genome-wide association analyses 在全基因组关联分析中整合多基因和个体SNP效应
Nick V. L. Serão, J. Beever, Dan B. Faulkner, S. Rodriguez-Zas
The lack of consideration of polygenic effects in genome-wide association studies (GWAS) may bias the results in complex traits controlled by multiple genes. The goal of this study is to develop a composite-GWAS model that identifies individual SNPs while adjusting for polygenic effects. The complex trait residual feed intake (RFI), an indicator of the feed efficiency based on maintenance and growth, was modeled. RFI and genotypic data (5,910 SNPs from chromosomes 3, 11 and 24) from 1,387 steers from different breeds and receiving different diets were analyzed, with and without the additive polygenic effect. The model included the fixed effects of days of feed, diet, breed and interaction between diet and breed, and the random effects of contemporary group and additive polygenic effect. A total of 69 and 141 SNPs were detected (P-value < 0.01) with the model including and excluding polygenic effects, respectively. The higher number of SNPs identified by the second model confirms that ignoring polygenic effects in GWAS of multi-gene traits can lead to false positives due to linkage disequilibrium. Seven SNPs (P-value < 0.001), four in chromosomes 3, two in chromosome 11 and one in chromosome 24, were detected using the polygenic model. Two SNPs, one from chromosome 3 and one from 11 are located within coding gene regions. Our results demonstrate the need to use composite-GWAS that include polygenic effects in complex multi-gene traits. These results indicated that the genetic improvement of feed efficiency in beef cattle may be accelerated by the incorporation of these markers in genomic selection strategies.
全基因组关联研究(GWAS)缺乏对多基因效应的考虑,可能会使多基因控制的复杂性状的研究结果产生偏差。本研究的目标是开发一种复合gwas模型,在调整多基因效应的同时识别单个snp。建立了基于维持和生长的饲料效率指标——复合性状剩余采食量(RFI)模型。对1387头饲喂不同饲粮的不同品种肉牛的RFI和基因型数据(来自第3、11和24号染色体的5,910个snp)进行了分析,并考虑了加性多基因效应和不加性多基因效应。模型包括饲料日数、日粮日数、品种日数和日粮与品种相互作用的固定效应,当代群效应和加性多基因效应的随机效应。在模型中分别检测到69个和141个snp (p值< 0.01)。第二种模型鉴定出的snp数量较多,证实了忽略多基因性状GWAS中的多基因效应可能会由于连锁不平衡而导致假阳性。采用多基因模型共检测到7个snp (p值< 0.001),其中4个位于第3染色体,2个位于第11染色体,1个位于第24染色体。两个snp,一个来自3号染色体,一个来自11号染色体,位于编码基因区域。我们的结果表明,有必要在复杂的多基因性状中使用包括多基因效应的复合gwas。这些结果表明,将这些标记纳入基因组选择策略可能会加速肉牛饲料效率的遗传改良。
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引用次数: 4
Identifying Ovarian Cancer Chemotherapy Response Relevant Gene Cliques 卵巢癌化疗反应相关基因群的鉴定
Yan-E. Li, Juan Zhang, Bin Han, Lihua Li
Operation with adjuvant chemotherapy is still the principal means to treat Ovarian cancer. Identifying Ovarian Cancer Chemotherapy Response (OCCR) relevant genes and describe their interactions is thus an important issue. However the problems of high dimensional micro array data and the scarcity of biological priors make building a complete OCCR biological network intractable. To this end, we combine liquid association (LA) algorithm with biological knowledgebase searching to identify OCCR relevant gene clique and describe their interactions. Rather than trying to build a gene network, our approach focus on identifying OCCR relevant gene cliques and then patching them up. Statistical analysis and biological validation show that the identified gene cliques play important roles in tumor genesis, immunity, cells proliferation and migration etc and significantly OCCR relevant. More importantly, the connection of independent gene cliques is established and the associations of genes are described. Methodologically, the proposed method avoids the problem of complex computation, relies only on available biological priors and provides a novel way to build gene network.
手术配合化疗仍是治疗卵巢癌的主要手段。因此,确定卵巢癌化疗反应(OCCR)相关基因并描述其相互作用是一个重要的问题。然而,微阵列数据的高维性和生物先验的稀缺性使得构建一个完整的OCCR生物网络变得非常困难。为此,我们将液体关联(LA)算法与生物知识库搜索相结合,识别OCCR相关基因团,并描述它们之间的相互作用。我们的方法不是试图建立一个基因网络,而是专注于识别OCCR相关的基因集团,然后将它们修补起来。统计分析和生物学验证表明,所鉴定的基因团在肿瘤发生、免疫、细胞增殖和迁移等方面发挥重要作用,与OCCR显著相关。更重要的是,建立了独立基因集团之间的联系,并描述了基因之间的关联。在方法上,该方法避免了复杂的计算问题,只依赖于现有的生物先验,为构建基因网络提供了一种新的途径。
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引用次数: 0
Decision Support in Safety Intelligence Using Pharmaconnect Knowledgebase 基于Pharmaconnect知识库的安全智能决策支持
S. Matis, Matt Clark, Marcus Bjäreland, Brian Takasaki, N. Mian, S. Muresan, Sorona Popa
On average it takes approximately 13 years and over 1 billion dollars to take a new medical entity (NME) from a concept to an approved product. As high as 40% of the drugs fail to make it thru to market at a significant cost and even with the best of preclinical testing some do cause unexpected or “idiosyncratic” toxicity. In order to reduce the length of the development timeline, support problem solving, provide improved decision making and reduce late stage attrition, many pharmaceutical companies are developing methodology to predict safety issues earlier in this process. While the exchange of scientific knowledge is still primarily thru the published medical literature, advances in semantic technology have dramatically changed the way a scientist accesses data and information. In particular, ontology development coupled with natural language processing, have made a huge impact on the review of the scientific literature and extraction of data from internal and external sources. Creation of highly linked knowledge bases enables the development of predictive methods as well as supports problem solving. These activities have been shown to be highly useful in reducing time and effort. The Knowledge Engineering initiative within AstraZeneca has recently delivered the first version of a knowledgebase that integrates internal and external evidence for connections between key concepts such as targets, pathways, compounds, diseases, preclinical, and clinical outcome from Chemistry, Competitive, Disease and Safety Intelligence workstreams. This talk will describe the system; demonstrate the impact of this new platform with specific examples from Safety, and discuss lessons learned during its development. 2011 IEEE International Conference on Bioinformatics and Biomedicine 978-0-7695-4574-5/11 $26.00 © 2011 IEEE DOI 10.1109/BIBM.2011.135 661
一个新的医疗实体(NME)从一个概念到一个批准的产品,平均需要大约13年和超过10亿美元。高达40%的药物未能以高昂的成本进入市场,即使进行了最好的临床前测试,一些药物也会产生意想不到的或“特殊”的毒性。为了缩短开发时间,支持问题的解决,提供改进的决策并减少后期的人员流失,许多制药公司正在开发方法来预测该过程的早期安全性问题。虽然科学知识的交流仍然主要是通过发表的医学文献,但语义技术的进步已经极大地改变了科学家获取数据和信息的方式。特别是,本体的发展与自然语言处理相结合,对科学文献的审查和从内部和外部来源提取数据产生了巨大的影响。创建高度关联的知识库可以开发预测方法,并支持解决问题。这些活动已被证明在减少时间和精力方面非常有用。阿斯利康的知识工程计划最近发布了第一版知识库,该知识库集成了来自化学、竞争、疾病和安全情报工作流程的关键概念(如靶点、途径、化合物、疾病、临床前和临床结果)之间联系的内部和外部证据。这次演讲将描述这个系统;用来自Safety的具体例子展示这个新平台的影响,并讨论在其开发过程中获得的经验教训。2011 IEEE国际生物信息学与生物医学会议978-0-7695-4574-5/11 $26.00©2011 IEEE DOI 10.1109/BIBM.2011.135 661
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引用次数: 0
Lessons learned in improving the adoption of a real-time NLP decision support system 改进采用实时自然语言处理决策支持系统的经验教训
Yang Huang, D. Zisook, Yunan Chen, M. Selter, P. Minardi, J. Mattison
While most research in the NLP domain focuses on information accuracy, the adoption of NLP applications in healthcare extends beyond technical innovations. This study investigates the adoption issues of an NLP application in three different field sites. Using both quantitative log analysis and qualitative user interviews, we identified four main factors that affect NLP adoption: organizational culture and support, system usability, information quality and system reliability. These factors must be considered to ensure successful adoption of NLP applications that provide real-time decision support in a clinical care setting.
虽然NLP领域的大多数研究都集中在信息准确性上,但在医疗保健领域采用NLP应用的范围超出了技术创新。本研究调查了在三个不同的现场采用NLP应用程序的问题。通过定量日志分析和定性用户访谈,我们确定了影响NLP采用的四个主要因素:组织文化和支持、系统可用性、信息质量和系统可靠性。这些因素必须考虑,以确保成功采用NLP应用程序,在临床护理设置提供实时决策支持。
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引用次数: 0
Reconstruction of gene regulatory networks by stepwise multiple linear regression from time-series microarray data 基于时间序列微阵列数据的逐步多元线性回归基因调控网络重构
Yiqian Zhou, Jacqueline Gerhart, A. Sacan
Gene regulatory networks provide a powerful abstraction of the complex interactions among genes involved in functional pathways. Experimental determination of these interactions using a classical experimental method, although of extreme value, is laborious and prohibitive at large scales. Over the last decade, a number of computational approaches have been developed to infer gene regulatory networks from high-throughput experimental data. In this study, we introduce a new algorithm for regulatory network inference, based on stepwise multiple regression of time-series microarray data. Compared to other existing methods, our regression-based method provides a clear interpretation of the inferred interactions. The statistical significance associated with each prediction can be utilized to rank the interactions, which is important in prioritization of predictions for further experimental verification. We demonstrate the performance of our approach on a well-known yeast cell cycle pathway and show that it makes more accurate predictions than existing methods.
基因调控网络为参与功能通路的基因之间复杂的相互作用提供了一个强有力的抽象。使用经典实验方法对这些相互作用进行实验测定,虽然具有极高的价值,但在大尺度上是费力和令人望而却步的。在过去的十年中,已经开发了许多计算方法来从高通量实验数据中推断基因调控网络。在这项研究中,我们引入了一种新的基于时序微阵列数据逐步多元回归的调节网络推理算法。与其他现有方法相比,我们基于回归的方法对推断的相互作用提供了清晰的解释。与每个预测相关的统计显著性可以用来对相互作用进行排序,这对于进一步实验验证预测的优先级很重要。我们证明了我们的方法在一个众所周知的酵母细胞周期途径上的表现,并表明它比现有的方法做出更准确的预测。
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引用次数: 1
期刊
2011 IEEE International Conference on Bioinformatics and Biomedicine Workshops (BIBMW)
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