Statistical And Computational Methods For Molecular Biology And Biomedicine

分子生物学和生物医学的统计和计算方法

• 批准号: 8565482
• 负责人: peter j munson
• 金额: $ 33.16万
• 依托单位: CENTER FOR INFORMATION TECHNOLOGY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8565482
• 关键词: Address; Affect; Agreement; Algorithms; Anemia; Area; Axon; Binding; Biological; Biology; Biomedical Engineering; Biomedical Research; Bioreactors; Blood capillaries; Brain; Caliber; Cell Count; Cell Culture Techniques; Cells; Cellular biology; Characteristics; Chicago; Childhood; Classification; Clinical; Collaborations; Complex; Computer Architectures; Computing Methodologies; Core Facility; DNA; Data; Dendrites; Development; Devices; Diffusion; Drosophila genus; Engineering; Environment; Erythrocytes; France; Functional Magnetic Resonance Imaging; Genes; Genomics; Goals; Hemoglobin; Human; Hydrogels; Image; Immune; Information Technology; International; Investigation; Joints; Laboratories; Language; Learning; Liquid substance; Malaria; Manuscripts; Measurement; Measures; Metabolism; Methods; Microdissection; Modeling; Molecular; Molecular Biology; Myelin; National Cancer Institute; National Institute of Allergy and Infectious Disease; National Institute of Biomedical Imaging and Bioengineering; National Institute of Child Health and Human Development; National Institute of Mental Health; National Institute of Neurological Disorders and Stroke; Nature; Network-based; Neuroglia; Neurons; Nodal; Normal Cell; Nuclear Extract; Nuclear Proteins; Oxygen; Paper; Parasites; Pathology; Patients; Pattern; Physics; Plasmodium; Population Dynamics; Population Study; Preparation; Process; Proteins; Publishing; Recurrence; Research; Research Personnel; Resource Sharing; Retinal; Role; Science; Signal Transduction; Silicones; Simulate; Skin; Statistical Computing; Statistical Methods; Statistical Models; Structure; Tail; Techniques; Technology; Tertiary Protein Structure; Thalassemia; Theoretical Studies; Thick; Tissue Sample; Tissues; Transport Process; United States National Institutes of Health; Universities; Visit; Weight; Width; Work; base; capillary; cell growth; computational neuroscience; density; epidemiology study; fitness; follow-up; human disease; improved; international center; mathematical model; nervous system development; neurotoxicology; novel; operation; physical science; pressure; professor; programs; protein folding; protein structure; relating to nervous system; reproductive; retinal neuron; simulation; social; symposium; theories; three dimensional structure; transmission process; vector; web site

In a joint study with investigators in Laboratory of Molecular Biology, NCI and Institut National de la Recherche Agronomique (INRA), France, we attacked the problem of protein structure classification, with the goal of improving automated methods for recognizing and classifying protein domains in three dimensional structures. We have recently shown that two distinct structure similarity measures (VAST and SHEBA) can obtain at best about 75-80% agreement with a standard manually curated protein classification (SCOP), calling into question the existence of sharp boundaries between protein "folds". We found that automatic classifications differ little from each other. We have developed three related algorithms for defining domains based on recurrence of similar structural fragments in other structural contexts in other proteins in the PDB. Starting with a list of recurring fragments similar to the query structure, the algorithms determine whether and where to divide the query into domains. Some domains appear to be discontinuous within the structure, indicating an ancient insertion in the underlying DNA. A web-site which calculates this algorithm was developed and published. With an investigator in the Division of International Epidemiology and Population Studies, Fogarty International Center, and with a professor from Loyola University Chicago visiting the Laboratory of Malaria and Vector Research, NIAID, we have developed a phenomenological model of population dynamics of the transmissible form of the malaria parasite, the gametocytes. At present we are studying the mechanisms by which host immune pressure against gametocytes (as well as against 'other intrahost forms of the parasite) could modulate gametocyte density and duration of gametocyte survival in the host. We are also investigating the difference in transmission strategies between the different Plasmodium species which cause human disease. A paper is currently under referee review and a second paper is being prepared for referee review. With a team of investigators from the Program in Physical Biology, NICHD, we are studying the affects of human hemoglobin abnormalities on the reproductive fitness of malaria parasites. We have demonstrated experimentally that malaria parasites reproduce at a lower rate in erythrocytes from patients with Thalassemia anemia. A paper is being prepared for referee review. With consortium of investigators from (1) Laboratory of Neurotoxicology, National Institute of Mental Health, (2) Program in Physical Biology, (NICHD), (3) Cell Biology and Metabolism Program, NICHD, (4) Laboratory of Pathology, National Cancer Institute, (5) Computational Bioscience and Engineering Laboratory, Division of Computational Bioscience, Center for Information Technology, (6) Biomedical Engineering and Physical Science Shared Resource, National Institute of Biomedical Imaging and Bioengineering, we are working of a model of the thermal and fluid transport processes that occur in the operation of expression microdissection (xMD). This is a newly developed method of extraction large number of cells from a tissue sample which is very promising for pathology, but both basic engineering development and a better theoretical understanding of its operations are needed before this technology can be fully exploited, either in an NIH core facility or for commercial distribution. We have demonstrated that XMD can extract nuclear materials from tissue samples and that nuclear proteins are captured undamaged by such extractions. A paper is being prepared for referee review. With an investigator in Laboratory of Gene Regulating and Development, NICHD, we are working on classification of the topology of retinal neurons of Drosophila. Distinct patterns of dendritic branching are associated with expression of certain genes in such neurons. The development of a "topology" classifier is helping to guide studies of the intercellular environment in the retinal. For example, one question we have answered is that the branching of dendrites is not a simple Poisson process. With a consortium of investigators from (1) Laboratory of Cell Biology, NCI, and (2) Computational Bioscience and Engineering Laboratory, Division of Computational Bioscience, CIT, we are developing a model of diffusion of oxygen through a special bioreactor which will provide both a 3D matrix for cell growth and capillary-like processes for oxygen delivery to cells. The capillary-like processes will be made from silicone hydrogels. At present the device is under engineering development. In a project with investigators of NIMH, we compare cortical network architectures to human brain networks obtained using diffusion spectrum imaging (DSI) and fMRI, as well as a number of other (non-neural) weighted complex networks, like scientific collaboration networks, airline networks, etc. Our study reveals novel and robust weight organization particularly pronounced in the networks with biological origin (neural, gene), but also in different social and language (word) networks. Additionally, using simulations, we show that such network architecture can be obtained using local learning rules that adjust the weights in the network based on the past interactions between the nodes. A manuscript describing this work has been published in Nature Physics in April of 2012. Continuation of this work is under way and focuses on the learning rules. This work has been presented at The Bernstein Conference on Computational Neuroscience in Sept, 2012. In a continuing project with investigators in the Program on Pediatric Imaging and Tissue Sciences (PPITS), NICHD we conduct a theoretical study of the observed skewed and heavy-tailed axon diamater distribution. We show that the observed distributions conforms to a heavy-tailed distribution with parametric form that optimizes the informative upper bound (IUB) as well as the information capacity. A manuscript describing this work is submitted to PLOS ONE in June, 2012. In a follow-up project, the distribution developed based on the optimal IUB characteristics has been implemented and applied to simulated and experimental data, yielding improved measurements of the axon diameter distributions. In a new project with investigators from the Program on Pediatric Imaging and Tissue Sciences (PPITS), NICHD and the Nervous System Development and Plasticity Section, NINDS, we use the cable theory as a theoretical framework to predict how the changes in myelin thickness, as well as the increase in the nodal width, affects the propagation of the signals along a myelinated axon. Both of these are regulated by the surrounding glial cells and dependent on the level of activity present in an axon. The theoretical predictions are implemented in Mathematica and are compared with the experimentally observed values, with the ultimate goal of addressing the role of myelinating glia in learning and plasticity. A manuscript describing this work is in preparation. In a new project with investigators from the Laboratory of Clinical and Developmental Genomics, NICHD we study neuronal cultures created by reprogramming skin cells from autistic patients as well as normals. It is a part of a larger study addressing the molecular and cellular changes that occur in the autistic brain during the development. In the current study the goal is to identify the changes in the network structure, or in the activity profile of different cells that distinguishes the normal cell cultures from those of autistic patients.

在与NCI分子生物学实验室和法国国家农学研究所（INRA）的研究人员的联合研究中，我们研究了蛋白质结构分类问题，目的是改进三维结构中蛋白质结构域识别和分类的自动化方法。我们最近的研究表明，两种不同的结构相似性度量（VAST和SHEBA）与标准的人工整理蛋白质分类（SCOP）最多可以获得75-80%的一致性，这对蛋白质“折叠”之间是否存在明显边界提出了质疑。我们发现自动分类彼此之间差别不大。我们已经开发了三种相关的算法，用于根据PDB中其他蛋白质的其他结构背景中相似结构片段的复发来定义结构域。从类似于查询结构的重复片段列表开始，算法确定是否以及在何处将查询划分为域。一些结构域在结构中似乎是不连续的，表明在潜在的DNA中有一个古老的插入。一个计算该算法的网站被开发并发布。

项目成果

A CTRW-based model of time-resolved fluorescence lifetime imaging in a turbid medium.

• DOI: 10.1016/j.optcom.2010.06.099
• 发表时间: 2010-12-01
• 期刊: OPTICS COMMUNICATIONS
• 影响因子: 2.4
• 作者: Chernomordik, Victor;Gandjbakhche, Amir H.;Hassan, Moinuddin;Pajevic, Sinisa;Weiss, George H.
• 通讯作者: Weiss, George H.

Spatial link between nucleoli and expression of the Zac1 gene.

• DOI: 10.1007/s00412-009-0229-1
• 发表时间: 2009-12
• 期刊: Chromosoma
• 影响因子: 1.6
• 作者: Royo F;Paz N;Espinosa L;McQueen PG;Vellón L;Parada LA
• 通讯作者: Parada LA