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2012 IEEE Second International Conference on Healthcare Informatics, Imaging and Systems Biology最新文献

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A Comparison of Computational Approaches in the Molecular Identification of Pathogenic Organisms 病原生物分子鉴定计算方法的比较
D. Bastola, Scott P. McGrath, S. Bhowmick, I. Thapa
Molecular based identification of pathogenic organism is becoming a routine procedure in many diagnostic laboratories. Ribosomal RNA is particularly the most popular choice for this purpose. Although, other targets such as `cytochrome b', `rpoB' and `actin' are highly effective, they have not been extensively used. This could be due to the lack of effective data collection method. We used sequence based exhaustive search of public sequence database to obtain all target sequences. This approach is currently being extended to collect such molecular targets for Nocardia and other slow growing medically important organisms.
病原生物的分子鉴定正在成为许多诊断实验室的常规程序。核糖体RNA是最受欢迎的选择。虽然其他靶标如“细胞色素b”、“rpoB”和“肌动蛋白”是非常有效的,但它们还没有被广泛使用。这可能是由于缺乏有效的数据收集方法。我们使用基于序列的穷举搜索公共序列数据库来获得所有目标序列。目前,这种方法正在被推广到诺卡菌和其他生长缓慢的医学重要生物的分子靶点。
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引用次数: 0
Integrating Transcriptome and Proteome Information for the Analysis of Alternative Splicing 整合转录组和蛋白质组信息分析选择性剪接
J. E. Kroll, J. E. Souza, B. Stransky, G. D. Souza, S. J. Souza
Summary form only given. Alternative splicing events (AS) are among the most significant factors determining the complexity of multi-cellular organisms. Most, if not all, multi-exonic human genes undergo AS. Many AS events are involved in the etiology of cancer, among many other common human disorders. The emergence of next-generation sequencing offers a unique opportunity to explore the variability generated by AS in an exhaustive way. Furthermore, recent developments in new mass-spectometry platforms have allowed a deeper survey of the human proteome. Here, an analysis of intron retention, the most rare type of AS, was performed integrating transcriptome and proteome data. Intron retention events were evaluated in relation to several features, focusing on whether they had biological significance or whether they were just spurious products from the splicing machinery. For the transcriptome analysis, the following dataset was used: 30,678 RefSeqs, 258,444 mRNAs, 6,987,423 ESTs and 9,565,439 sequences derived from NGS. For the proteome analysis, data from Geiger et al., MCP, 2012 were used. We were able to detect an intron retention event for 48% of all human genes. Confirming a previous publication from our group [1], these events are enriched at the 3'and 5'untranslated regions (UTRs). Retained introns were significantly enriched with coding potential, which supports a biological role for these events. Furthermore, they were enriched for targets of microRNAs, suggesting a role of this type of AS in the regulation of expression induced by these non-coding RNAs. A significant number of events were detected at the proteome level. This information was integrated together with transcriptome data to further explore the role of intron retention in many biological phenomena.
只提供摘要形式。选择性剪接事件(AS)是决定多细胞生物复杂性的最重要因素之一。大多数(如果不是全部的话)多外显子的人类基因都会经历AS。在许多其他常见的人类疾病中,许多AS事件与癌症的病因有关。下一代测序的出现提供了一个独特的机会,以详尽的方式探索由AS产生的变异性。此外,新的质谱平台的最新发展已经允许对人类蛋白质组进行更深入的调查。在这里,对最罕见的AS类型内含子保留进行分析,整合转录组和蛋白质组数据。内含子保留事件与几个特征有关,重点是它们是否具有生物学意义,或者它们是否只是剪接机制的虚假产物。转录组分析使用了以下数据集:30,678个RefSeqs, 258,444个mrna, 6,987,423个ESTs和9,565,439个来自NGS的序列。蛋白质组分析使用Geiger et al., MCP, 2012年的数据。我们能够检测到48%的人类基因的内含子保留事件。证实了我们小组[1]先前发表的一篇文章,这些事件在3'和5'非翻译区(utr)富集。保留的内含子显著富集了编码潜能,这支持了这些事件的生物学作用。此外,它们富含microrna的靶标,这表明这种类型的AS在这些非编码rna诱导的表达调控中起作用。在蛋白质组水平上检测到大量事件。这些信息与转录组数据相结合,进一步探索内含子保留在许多生物现象中的作用。
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引用次数: 1
InSilico-ChIP: A Coregulation and Evolutionary Conservation Based Transcription Factor and Target Gene Predictor InSilico-ChIP:一个基于协同调节和进化保护的转录因子和靶基因预测因子
M. Munoz, A. Zambon
Chromatin Immunoprecipitation followed by high-content sequencing (ChIP-seq) is a powerful approach for identifying bonafide transcription factor (TF) binding sites, however these studies can be difficult, time-consuming and costly. They require ChIP-validated antibodies and a priori knowledge of which TF to pull down. Moreover, to gain further mechanistic insights, transcriptomic data is required to determine if TF binding alters proximal gene expression. Determining regulatory pathways from expression data is not an easy task. The typical result of a gene expression experiment, a set of co-regulated genes, may not include the relevant TF at all. Many such factors become active through mechanisms other than a change in their level of expression. To understand how such a set of genes is co-regulated, it is necessary to find evidence of shared TF binding sites (TFBS). This approach presents its own set of problems. TFBS are identified by short sequences that can exist by chance without being biologically functional. An evolutionary perspective is required to consider only those functionally important sites that are conserved between the promoters of the genes in question and those of their orthologs in related species. Furthermore, the common occurrence of short TFBS makes it necessary to consider only those TFs that are significantly more common in the co-regulated genes than in the genome (or microarray) as a whole. InSilico-ChIP is a precomputed database of evolutionarily conserved TFBS for various species, which accepts a set of genes and quickly returns the conserved TFs that are statistically over-represented in the proximal promoter regions of those genes. It allows new species data to be created using only a whole genome alignment with a related species and gene locations. Several methods of identifying TF binding sites can be used, varying in alignment type, location, conservation restrictions, and TFBS matrices used to analyze the promoter regions.
染色质免疫沉淀与高含量测序(ChIP-seq)是鉴定真实转录因子(TF)结合位点的一种有效方法,然而这些研究可能困难,耗时且昂贵。它们需要经过chip验证的抗体和要拉下哪个TF的先验知识。此外,为了获得进一步的机制见解,需要转录组学数据来确定TF结合是否改变近端基因表达。从表达数据中确定调控途径并不是一件容易的事。基因表达实验的典型结果是一组共调控基因,可能根本不包括相关的TF。许多这样的因素不是通过表达水平的变化,而是通过机制变得活跃起来。为了了解这组基因是如何协同调节的,有必要找到共享TF结合位点(TFBS)的证据。这种方法有其自身的问题。TFBS是通过短序列识别的,这些短序列可以偶然存在,而不具有生物学功能。从进化的角度来看,只考虑那些在有问题的基因启动子和相关物种的同源基因启动子之间保守的功能重要位点。此外,短TFBS的普遍存在使得我们有必要只考虑那些在共调控基因中比在整个基因组(或微阵列)中更常见的TFs。insilicon - chip是一个预先计算的各种物种的进化保守TFBS数据库,它接受一组基因,并迅速返回在这些基因的近端启动子区域统计上过度代表的保守tffs。它允许只使用与相关物种和基因位置的全基因组比对就可以创建新的物种数据。可以使用几种识别TF结合位点的方法,这些方法在排列类型、位置、保护限制和用于分析启动子区域的TFBS矩阵方面有所不同。
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引用次数: 0
A Network Approach for Computational Drug Repositioning 一种计算药物重新定位的网络方法
Jiao Li, Zhiyong Lu
Computational drug repositioning offers promise for discovering new uses of existing drugs, as drug related molecular, chemical, and clinical information has increased over the past decade and become broadly accessible. In this study, we present a new computational approach for identifying potential new indications of an existing drug through its relation to similar drugs in disease-drug-target network. When measuring drug pairwise similarly, we used a bipartite-graph based method which combined similarity of drug compound structures, similarity of target protein profiles, and interaction between target proteins. In evaluation, our method compared favorably to the state of the art, achieving AUC of 0.888. The results indicated that our method is able to identify drug repositioning opportunities by exploring complex relationships in disease-drug-target network.
计算药物重新定位为发现现有药物的新用途提供了希望,因为与药物相关的分子、化学和临床信息在过去十年中不断增加,并且可以广泛获取。在这项研究中,我们提出了一种新的计算方法,通过其与疾病-药物靶标网络中类似药物的关系来识别现有药物的潜在新适应症。在测量药物两两相似度时,我们使用了基于双部分图的方法,该方法结合了药物化合物结构的相似性、靶蛋白谱的相似性和靶蛋白之间的相互作用。在评估中,我们的方法优于目前的技术水平,实现了0.888的AUC。结果表明,我们的方法能够通过探索疾病-药物靶标网络中的复杂关系来识别药物重新定位的机会。
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引用次数: 1
Using MapReduce for Large-Scale Medical Image Analysis 基于MapReduce的大规模医学图像分析
Dimitrios Markonis, Roger Schaer, Ivan Eggel, H. Müller, A. Depeursinge
In this paper, MapReduce is used to speed up and make possible three large-scale medical image processing use-cases: (i) parameter optimization for lung texture classification using support vector machines (SVM), (ii) content-based medical image indexing, and (iii) three-dimensional directional wavelet analysis for solid texture classification.
本文利用MapReduce加速并实现了三个大规模医学图像处理用例:(i)基于支持向量机(SVM)的肺纹理分类参数优化,(ii)基于内容的医学图像索引,(iii)用于实体纹理分类的三维定向小波分析。
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引用次数: 64
Modelling the Effects of Genetic Changes in Tumour Progression 模拟肿瘤进展中基因变化的影响
Vanderson Silva, F. Santana, B. Stransky, S. J. Souza
Tumours can be considered a set of cells that accumulate genetic and epigenetic alterations. According to the Multi-stage Hit theory, the transformation of a normal into a tumour cell involves a number of limiting events that occur in a number of discrete stages (driver mutations). However, not all mutations that occur in the cell are directly involved in the development of cancer and some probably do not contribute in any way (passenger mutations). Moreover, the process of tumour evolution is punctuated by selection of advantageous mutations and clonal expansions. Actually, it is not known how many limiting-events, i.e., how many driver mutations are necessary or sufficient to promote a carcinogenic process. This conjecture should be explored and tested - mathematically and statistically, with the availability of genomic data on databanks. In this work, we explore the model proposed by Bozic and collaborators (2010) that describes the evolution of the tumour according to a Galton-Watson process. Besides, the model gives the relation between the numbers of passenger mutations giving a specific number of driver mutations. We intend to explore some of the model parameters and test some premises about the number of drive mutations and selective advantage, comparing the simulation results with genomic data from colorectal cancer patients. The genomic data was obtained from the DBMutation (http://www.bioinformatics-brazil.org/dbmutation/), a comprehensive database for genomic mutations in cancer. We expect that correlations between driver mutations and the time evolution of tumour process will facilitate the interpretation of genomic information, to make them useful and applicable to clinical oncology.
肿瘤可以被认为是一组积累遗传和表观遗传改变的细胞。根据多阶段Hit理论,正常细胞向肿瘤细胞的转变涉及到许多限制事件,这些事件发生在许多离散的阶段(驱动突变)。然而,并非细胞中发生的所有突变都直接与癌症的发展有关,有些突变可能根本没有作用(乘客突变)。此外,肿瘤进化的过程被有利突变的选择和克隆扩增打断。实际上,目前尚不清楚有多少限制事件,即有多少驱动突变是必要的或足以促进致癌过程的。这一猜想应该得到探索和检验——用数学和统计方法,利用数据库中基因组数据的可用性。在这项工作中,我们探索了Bozic及其合作者(2010)提出的模型,该模型根据高尔顿-沃森过程描述了肿瘤的进化。此外,该模型给出了给定特定驾驶员突变数时乘客突变数之间的关系。我们打算探索一些模型参数,测试一些关于驱动突变数量和选择优势的前提,并将模拟结果与结直肠癌患者的基因组数据进行比较。基因组数据来自DBMutation (http://www.bioinformatics-brazil.org/dbmutation/),这是一个关于癌症基因组突变的综合数据库。我们期望驱动突变和肿瘤过程时间演化之间的相关性将促进基因组信息的解释,使其对临床肿瘤学有用和适用。
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引用次数: 0
Automatically Extracting Sentences from Medline Citations to Support Clinicians' Information Needs 自动从Medline引文中提取句子以支持临床医生的信息需求
Siddhartha R. Jonnalagadda, G. Fiol, Richard Medlin, C. Weir, M. Fiszman, Javed Mostafa, Hongfang Liu
Online health knowledge resources contain answers to most of the information needs raised by clinicians in the course of care. However, significant barriers limit the use of these resources for decision-making, especially clinicians' lack of time. Existing solutions are less optimal when information needs cannot be met without substantial cognitive effort and time. Objectives: In this study, we assessed the feasibility of automatically generating knowledge summaries for a particular clinical topic composed of relevant sentences extracted from Medline citations. Methods: The proposed approach combines information retrieval and semantic information extraction techniques to identify relevant sentences from Medline abstracts. We assessed this approach in two case studies on the treatment alternatives for depression and Alzheimer's disease. Results: A total of 515 out of 564 (91.3%) sentences retrieved in the two case studies were relevant to the topic of interest. About one third of the relevant sentences described factual knowledge or a study conclusion that can be used for supporting information needs at the point of care. Conclusions: Our proposed technical approach to helping clinicians meet their information needs is promising. The approach can be extended for other knowledge resources and information need types.
在线卫生知识资源包含了临床医生在护理过程中提出的大多数信息需求的答案。然而,重大障碍限制了这些资源用于决策的使用,特别是临床医生缺乏时间。当没有大量的认知努力和时间就无法满足信息需求时,现有的解决方案就不那么理想了。目的:在这项研究中,我们评估了自动生成特定临床主题知识摘要的可行性,该摘要由从Medline引文中提取的相关句子组成。方法:该方法结合信息检索和语义信息提取技术,从Medline摘要中识别相关句子。我们在两个关于抑郁症和阿尔茨海默病治疗方案的案例研究中评估了这种方法。结果:在两个案例研究中检索到的564个句子中,共有515个(91.3%)与感兴趣的主题相关。大约三分之一的相关句子描述了事实性知识或研究结论,可用于支持护理点的信息需求。结论:我们提出的技术方法帮助临床医生满足他们的信息需求是有希望的。该方法可以扩展到其他知识资源和信息需求类型。
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引用次数: 48
Pre-annotating Clinical Notes and Clinical Trial Announcements for Gold Standard Corpus Development: Evaluating the Impact on Annotation Speed and Potential Bias 为金标准语料库开发预注释临床笔记和临床试验公告:评估对注释速度和潜在偏倚的影响
T. Lingren, Louise Deléger, Katalin Molnár, Haijun Zhai, J. Meinzen-Derr, M. Kaiser, Laura Stoutenborough, Qi Li, I. Solti
In this study our aim was to present a series of experiments to evaluate the impact of pre-annotation: (1) on the speed of manual annotation of clinical notes and clinical trial announcements; and (2) test for potential bias if pre-annotation is utilized. The gold standard was 900 clinical trial announcements from clinicaltrials.gov website and 1655 clinical notes annotated for diagnoses, signs, symptoms, UMLS CUI and SNOMED CT codes. Two dictionary-based methods were used to pre-annotate the text. Annotation time savings ranged from 2.89% to 29.1% per entity. The pre-annotation did not reduce the IAA or annotator performance but reduced the time to annotate in every experiment. Dictionary-based pre-annotation is a feasible and practical method to reduce cost of annotation without introducing bias in the process.
在本研究中,我们的目的是通过一系列实验来评估预注释的影响:(1)对临床笔记和临床试验公告的手动注释速度的影响;(2)使用预标注进行潜在偏差检验。金标准是来自clinicaltrials.gov网站的900个临床试验公告和1655个临床笔记,其中注释了诊断、体征、症状、UMLS CUI和SNOMED CT代码。使用两种基于词典的方法对文本进行预注释。注释时间节省范围从2.89%到29.1%不等。预标注并未降低IAA和标注器的性能,但减少了每次实验的标注时间。基于词典的预标注是一种可行且实用的方法,可以在不引入偏见的情况下降低标注成本。
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引用次数: 6
Pulmonary Blood Vessels and Nodules Segmentation via Vessel Energy Function and Radius-Variable Sphere Model 基于血管能量函数和半径变球模型的肺血管和结节分割
Qingxiang Zhu, H. Xiong, Xiaoqian Jiang
To help diagnose the early stage of lung cancer, this paper studies pulmonary nodule and blood vessel detection and segmentation. Owing to the fact that variation in the shape and number of pulmonary blood vessels would reveal the progress of lung cancer, automatic segmentation of pulmonary nodules and blood vessels is desirable for chest computer-aided diagnosis (CAD) systems. The proposed algorithm is composed of four steps: pre-segmentation, structure enhancement, active evolution, and refinement. Through the initial extraction of 3D region growing, the line structure of vessel and blob-like structure of nodule would be enhanced by multi-scale filtering. In particular, the active evolution is devoted to the maximum likelihood estimation with a vessel energy function (VEF) of intensity, gradient, and structure. The VEF aims to shape a precise extraction by adapting all the cue distribution along the vessel region from nodules. Furthermore, a radius-variable sphere model is adopted to refine the contour with the smoothness of radius alone the centerline of the blood vessel. Finally, the proposed scheme is sufficiently evaluated to exceed the existing techniques on lung image database consortium (LIDC) database and DICOM images.
为了帮助肺癌的早期诊断,本文对肺结节和血管的检测与分割进行了研究。由于肺部血管的形状和数量的变化可以反映肺癌的进展,因此肺结节和血管的自动分割是胸部计算机辅助诊断(CAD)系统所需要的。该算法由四个步骤组成:预分割、结构增强、主动进化和细化。通过对三维区域生长的初始提取,通过多尺度滤波增强血管的线状结构和结节的斑点状结构。特别地,主动演化致力于用强度、梯度和结构的血管能量函数(VEF)进行最大似然估计。VEF的目的是通过适应结节血管区域的所有线索分布来形成精确的提取。在此基础上,采用变半径球模型对血管轮廓进行细化,使其半径仅为血管中心线的平滑度。最后,该方案经过充分的评估,超越了现有的肺图像数据库联盟(LIDC)数据库和DICOM图像技术。
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引用次数: 3
Small RNA Sequencing in microRNA Research 小RNA测序在微RNA研究中的应用
Hsei-Wei Wang
In this post-genomic era it is clear that the sum of the cellular gene expression state determines the cellular phenotypes. The challenge we now face is to keep up the bioinformatics analysis and to understand the genome blueprint. In our lab we applied and developed bioinformatics and systems biology tools for deciphering cancer and stem cell transcriptome data. Cancer stem-like cells were isolated as colonospheres from primary colon cancer tissues and cell lines and characterized their gene expression patterns and genetic networks. Expanded colon cancer spheres had many features of cancer stem cells, including chemoresistance and radioresistance, the ability to initiate tumor formation, and activation of epithelial-mesenchymal transition (EMT). SNAIL, an activator of EMT, was expressed at high levels by CRC colonospheres. smRNA-Seq and genetic network analyses revealed that SNAIL activates genes and microRNAs, such as IL8 and miR-146a, in colonospheres. Blocking IL-8 or miR-146a expression/activity disrupted SNAIL-induced stem cell-like features of colonospheres. Strategies that disrupt the SNAIL-IL8 and SNAIL-miR146a pathways can be developed to block tumor formation by colon cancer stem-like cells. We also applied our systems on brain tumor research. Atypical teratoid/rhabdoid tumor (AT/RT) is a highly malignant pediatric brain tumor often misdiagnosed as other embryonal brain tumors such as medulloblastoma (MB). AT/RT prognosis is much worse than MB, but the underlying mechanisms are unclear. We deciphered the miRNome patterns of AT/RT and MB by sequencing their small RNA fractions. Novel as well as known miRNAs were found deregulated in tumor cells. miR-221 and miR-222 are oncomiRs that can target several tumor suppressors. Further challenge will be to integrate RNA-seq information with systems biology and cloud computing tools.
在后基因组时代,很明显,细胞基因表达状态的总和决定了细胞表型。我们现在面临的挑战是保持生物信息学分析和理解基因组蓝图。在我们的实验室中,我们应用并开发了生物信息学和系统生物学工具来破译癌症和干细胞转录组数据。从原发性结肠癌组织和细胞系中分离出肿瘤干细胞样结肠球,并对其基因表达模式和遗传网络进行了表征。扩大的结肠癌球具有癌症干细胞的许多特征,包括化疗耐药和放射耐药,启动肿瘤形成的能力,以及上皮-间质转化(EMT)的激活。SNAIL是一种EMT激活因子,在结直肠癌结肠球中高水平表达。smRNA-Seq和遗传网络分析显示,SNAIL激活结肠球中的基因和microrna,如IL8和miR-146a。阻断IL-8或miR-146a表达/活性会破坏蜗牛诱导的结肠球干细胞样特征。破坏SNAIL-IL8和SNAIL-miR146a通路的策略可以被开发出来阻止结肠癌干细胞样细胞的肿瘤形成。我们还将我们的系统应用于脑肿瘤研究。非典型畸胎瘤/横纹肌样瘤(AT/RT)是一种高度恶性的小儿脑肿瘤,常被误诊为其他胚胎性脑肿瘤,如髓母细胞瘤。AT/RT预后比MB差得多,但潜在的机制尚不清楚。我们通过测序AT/RT和MB的小RNA片段来破译它们的miRNome模式。在肿瘤细胞中发现了新的和已知的mirna。miR-221和miR-222是可以靶向几种肿瘤抑制因子的肿瘤因子。进一步的挑战将是将RNA-seq信息与系统生物学和云计算工具相结合。
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引用次数: 0
期刊
2012 IEEE Second International Conference on Healthcare Informatics, Imaging and Systems Biology
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