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Large-scale analysis of human heavy chain V(D)J recombination patterns

Immunome Research 2008年第1期4卷 1-10页

作者： Volpe, Joseph M Kepler, Thomas B Center for Computational Immunology Duke University Durham NC United States Department of Immunology Duke Univeristy Medical Center Durham NC United States Department of Biostatistics and Bioinformatics Duke Univeristy Medical Center Durham NC United States Institute of Statistics and Decision Sciences Duke Univeristy Durham NC United States Computational Biology and Bioinformatics Graduate Program Institute for Genome Sciences and Policy Duke Univeristy Durham NC United States

Background. The processes involved in the somatic assembly of antigen receptor genes are unique to the immune system and are driven largely by random events. Subtle biases, however, may exist and provide clues to the molecular mechanisms involved in their assembly and selection. Large-scale efforts to provide baseline data about the genetic characteristics of immunoglobulin (Ig) genes and the mechanisms involved in their assembly have recently become possible due to the rapid growth of genetic databases. Results. We gathered and analyzed nearly 6,500 productive human Ig heavy chain genes and compared them with 325 non-productive Ig genes that were originally rearranged out of frame and therefore incapable of being biased by selection. We found evidence for differences in n-nucleotide tract length distributions which have interesting interpretations for the mechanisms involved in n-nucleotide polymerization. Additionally, we found striking statistical evidence for pairing preferences among D and J segments. We present a statistical model to support our hypothesis that these pairing biases are due to multiple sequential D-to-J rearrangements. Conclusion. We present here the most precise estimates of gene segment usage frequencies currently available along with analyses regarding n-nucleotide distributions and D-J segment pair preferences. Additionally, we provide the first statistical evidence that sequential D-J recombinations occur at the human heavy chain locus during B-cell ontogeny with an approximate frequency of 20%.

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Study on the immobilization of Ni-NTA and NTA on PMMA substrate base

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Key Engineering Materials 2008年 381-382卷 357-360页

作者： Chong, W.S. Kim, G.B. Hong, C.U. Department of Biomedical Engineering Graduate School Chonbuk National University Duckjin-Dong Jeonju Jeonbuk 561-756 Korea Republic of Education Program for 21st Century Chonbuk National University Research Institute of Clinical Medicine Duckjin-Dong Jeonju Jeonbuk 561-756 Korea Republic of Division of Bionics and Bioinformatics Collage of Engineering Chonbuk National University Duckjin-Dong Jeonju Jeonbuk 561-756 Korea Republic of

In this study, we attempts to develop a sensing method to detect mismatched DNA in order to diagnose cancer. The sensing method will be developed to use for early diagnosis of cancer. Thus, protein immobilization was applied on the surface of the sensor in order to facilitate the detection of mismatched DNA. This method was designed to achieve the Ni-His-Tag to selectively bond with MutS, which has a covalent bond with the His-Tag, by using Ni-NTA. This method is troublesome because it involves a number of repeated composition processes. This method need gold surface to immobilize NTA (nitrotriamino acid). But this process is very complicated and expensive cost. Therefore, we try to immobilize NTA using PMMA (poly methyl methacrylate) polymer in this research to improve this method. In this study revealed that we could directly immobilize the NTA to the PMMA substrate not used Gold substrate. Also, we could directly immobilize the MutS to the NTA using the EDC solution. In addition, we can expect that the mismatched DNA can be detected from the results.

关键词： Proteins

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Using a literature-based NMF model for discovering gene functional relationships

Using a literature-based NMF model for discovering gene func...

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IEEE International Conference on bioinformatics and Biomedicine Workshops (BIBMW)

作者： Elina Tjioe Michael Berry Ramin Homayouni Genome Science and Technology Graduate School University of Tennessee Knoxville TN USA Department of Electrical Engineering and Computer Science University of Tennessee Knoxville TN USA Bioinformatics Program Department of Biology University of Memphis Memphis TN USA

The rapid growth of the biomedical literature and genomic information presents a major challenge for determining the functional relationships among genes. In this study, we develop a Web-based bioinformatics software environment called FAUN or feature annotation using nonnegative matrix factorization (NMF) to facilitate both the discovery and classification of functional relationships among genes. Both the computational complexity and parameterization of NMF for processing gene sets are discussed. We tested FAUN on three manually constructed gene document collections, and then used it to analyze several microarray-derived gene sets obtained from studies of the developing cerebellum in normal and mutant mice. FAUN provides utilities for collaborative knowledge discovery and identification of new gene relationships from text streams and repositories (e.g., MEDLINE). It is particularly useful for the validation and analysis of gene associations suggested by microarray experimentation.

关键词： bioinformatics Genomics Data mining Matrix decomposition Large scale integration Feature extraction Iterative methods Biological system modeling Computer science Computational biology

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Study of equilibrium sense improvement displaying visual information

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Key Engineering Materials 2008年 381-382卷 369-372页

作者： Kim, G.B. Jeong, S.H. Chong, W.S. Kang, H.S. Kim, S.J. Kim, M.H. Hwang, J.W. Hong, C.U. Education Program for 21st Century Chonbuk National University Research Institute of Clinical Medicine Duckjin-Dong Jeonju Chonbuk 561-756 Korea Republic of Department of Computer Engineering Graduate School Chonbuk National University Duckjin-Dong Jeonju Chonbuk 561-756 Korea Republic of Department of Biomedical Engineering Graduate School Chonbuk National University Duckjin-Dong Jeonju Chonbuk 561-756 Korea Republic of Department of Pharmacology College of Veterinary Medicine Chonbuk National University Duckjin-Dong Jeonju Chonbuk 561-756 Korea Republic of Department of Bio and Applied Chemistry Iksan National College Ma-Dong Iksan Chonbuk 570-752 Korea Republic of Department of Thoracic and Cardiovascular Surgery Chonbuk National University Medical Schools Duckjin-Dong Jeonju Chonbuk 561-756 Korea Republic of Collage of Engineering Chonbuk National University Duckjin-Dong Jeonju Chonbuk 561-756 Korea Republic of Division of Bionics and Bioinformatics Collage of Engineering Chonbuk National University Duckjin-Dong Jeonju Chonbuk 561-756 Korea Republic of

The effectiveness of the visual feedback to improve ability with the sense and muscular strength of human in our bicycle system was quantitatively verified in our study. Experiments were performed to find the factors related to the training of equilibrium sense. The subjects consisted of young and the aged and the group of young people was compared against the group of the aged. We investigated three different training modes, non-visual feedback (NVF), visual feedback of the weight (VFW), and visual feedback of the center of pressure (VFC) and measured the riding time and speed, the weight shift, and the center of pressure (COP) for twenties and seventies. The results showed that the running capability of the young and the aged became much better after repeated training. In addition, it was found out that the ability to control postural balance and the capability of equilibrium sense were improved with the presentation of the visual feedback information. These results will be effective in the diagnosis of equilibrium sense and vestibular function with the aged.

关键词： Feedback

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Unexpected failure rates for modular assembly of engineered zinc fingers (vol 5, pg 374, 2008)

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NATURE METHODS 2008年第6期5卷 575-575页

作者： Ramirez, Cherie L. Foley, Jonathan E. Wright, David A. Mueller-Lerch, Felix Rahman, Shamim H. Cornu, Tatjana I. Winfrey, Ronnie J. Sander, Jeffry D. Fu, Fengli Townsend, Jeffrey A. Cathomen, Toni Voytas, Daniel F. Joung, J. Keith These authors contributed equally to this work. These authors contributed equally to this work. Department of Genetics Development and Cell Biology Iowa State University 1035A Roy J. Carver Co-Lab Ames Iowa 50011 USA. Charité Medical School Institute of Virology Hindenburgdamm 27 D-12203 Berlin Germany. Charité Medical School Institute of Virology Hindenburgdamm 27 D-12203 Berlin Germany. Charité Medical School Institute of Virology Hindenburgdamm 27 D-12203 Berlin Germany. Department of Genetics Development and Cell Biology Iowa State University 1035A Roy J. Carver Co-Lab Ames Iowa 50011 USA. Interdepartmental Graduate Program in Bioinformatics and Computational Biology 2114 Molecular Biology Building Iowa State University Ames Iowa 50011 USA. Interdepartmental Graduate Program in Bioinformatics and Computational Biology 2114 Molecular Biology Building Iowa State University Ames Iowa 50011 USA. Department of Genetics Development and Cell Biology Iowa State University 1035A Roy J. Carver Co-Lab Ames Iowa 50011 USA. Charité Medical School Institute of Virology Hindenburgdamm 27 D-12203 Berlin Germany. Department of Genetics Development and Cell Biology Iowa State University 1035A Roy J. Carver Co-Lab Ames Iowa 50011 USA. Department of Pathology Harvard Medical School Boston Massachusetts 02115 USA.

A letter to the editor is presented in response to an article on zinc fingers in a previous issue.

关键词： LETTERS to the editor ZINC

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eXpanda: An integrated platform for network analysis and visualization

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In Silico Biology 2007年第2期7卷 141-144页

作者： Negishi, Yoshiteru Nakamura, Hiroyuki Yachie, Nozomu Saito, Rintaro Tomita, Masaru Institute for Advanced Biosciences Keio University Fujisawa 252-8520 Japan Bioinformatics Program Graduate School of Media and Governance Keio University Fujisawa 252-8520 Japan Department of Environmental Information Keio University Fujisawa 252-8520 Japan

Analysis and visualization of biological networks, such as protein-protein and protein-DNA interactions, are crucially important toward obtaining a thorough understanding of living systems. Here, we present an integrative software platform, eXpanda, which enables an analysis of a very broad range of biological networks, with a special focus on the extraction of characteristic topologies which potentially function as units in the networks. eXpanda is provided as a Perl library which gives full-automatic connections to various biological databases via a Perl programmable interface and can perform topological analysis based on graph theory. The results of these analyses are visualizable by vector graphics. eXpanda is under GNU General Public License. Software package, detailed documentations, source codes, and some sample scripts are downloadable at http://***/expanda/. © 2007 IOS Press. All rights reserved.

关键词： Interactome Network analysis Network visualization Perl library Scalable Vector Graphics (SVG)

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Structural characterization of RNA-binding sites of proteins: Preliminary results

Structural characterization of RNA-binding sites of proteins...

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IEEE International Conference on bioinformatics and Biomedicine Workshops (BIBMW)

作者： Fadi Towfic David C. Gemperline Cornelia Caragea Feihong Wu Drena Dobbs Vasant Honavar Bioinformatics and Computational Biology Graduate Program Iowa State University Ames IA USA Department of Biology Department of Chemistry Carthage College Kenosha WI USA Department of Computer Science Iowa State University Ames IA USA Department of Genetics Development and Cell Biology Bioinformatics and Computational Biology Graduate Program Iowa State University Ames IA USA Department of Computer Science Bioinformatics and Computational Biology Graduate Program Iowa State University Ames IA USA

We explore whether protein-RNA interfaces differ from non-interfaces in terms of their structural features and whether structural features vary according to the type of the bound RNA (e.g., mRNA, siRNA...etc), using a non-redundant dataset of 147 protein chains extracted from protein-RNA complexes in the protein data bank. Our analysis of surface roughness, solid angle and CX value of amino acid residues for each of the protein chains in the dataset shows that: The protein-RNA interface residues tend to be protruding compared to non-interface residues and tend to have higher surface roughness and exhibit moderately convex or concave solid angles. Furthermore, the protein chains in protein-RNA interfaces that contain Viral RNA and rRNA significantly differ from those that contain dsRNA, mRNA siRNA, snRNA, SRP RNA and tRNA with respect to their CX values. The results of this analysis sug gests the possibility of using such structural features to reliably identify protein-RNA interface residues when the structure of the protein is available but the structures of complexes formed by the protein with RNA are not.

关键词： RNA Protein engineering Biology computing Amino acids bioinformatics Computer interfaces Rough surfaces Surface roughness Solids Machine learning

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A kinetic model for calcium dynamics in RAW 264.7 cells: 1. Mechanisms, parameters, and subpopulational variability

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Biophysical Journal 2007年第3期93卷 709-728页

作者： Maurya, Mano Ram Subramaniam, Shankar Department of Bioengineering University of California San Diego CA United States Department of Chemistry and Biochemistry University of California San Diego CA United States Graduate Program in Bioinformatics University of California San Diego CA United States Dept. of Bioengineering University of California San Diego San Diego CA 92093-0412 9500 Gilman Dr. United States

Calcium (Ca2+) is an important second messenger and has been the subject of numerous experimental measurements and mechanistic studies in intracellular signaling. Calcium profile can also serve as a useful cellular ph...

Calcium (Ca²⁺) is an important second messenger and has been the subject of numerous experimental measurements and mechanistic studies in intracellular signaling. Calcium profile can also serve as a useful cellular phenotype. Kinetic models of calcium dynamics provide quantitative insights into the calcium signaling networks. We report here the development of a complex kinetic model for calcium dynamics in RAW 264.7 cells stimulated by the C5a ligand. The model is developed using the vast number of measurements of in vivo calcium dynamics carried out in the Alliance for Cellular Signaling (AfCS) Laboratories. Ligand binding, phospholipase C-β (PLC-β) activation, inositol 1,4,5-trisphosphate (IP3) receptor (IP3R) dynamics, and calcium exchange with mitochondria and extracellular matrix have all been incorporated into the model. The experimental data include data from both native and knockdown cell lines. Subpopulational variability in measurements is addressed by allowing nonkinetic parameters to vary across datasets. The model predicts temporal response of Ca²⁺ concentration for various doses of C5a under different initial conditions. The optimized parameters for IP3R dynamics are in agreement with the legacy data. Further, the half-maximal effect concentration of C5a and the predicted dose response are comparable to those seen in AfCS measurements. Sensitivity analysis shows that the model is robust to parametric perturbations. © 2007 by the Biophysical Society.

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Simulation of developmental changes in action potentials with ventricular cell models

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Systems and Synthetic Biology 2007年第1期1卷 11-23页

作者： Itoh, Hitomi Naito, Yasuhiro Tomita, Masaru Institute for Advanced Biosciences Keio University Fujisawa Kanagawa 252-8520 Japan Bioinformatics Program Graduate School of Media and Governance Keio University Fujisawa Kanagawa 252-8520 Japan Japan Society for the Promotion of Science (DC1) Tokyo Japan Department of Environmental Information Keio University Fujisawa Kanagawa 252-8520 Japan

During cardiomyocyte development, early embryonic ventricular cells show spontaneous activity that disappears at a later stage. Dramatic changes in action potential are mediated by developmental changes in individual ionic currents. Hence, reconstruction of the individual ionic currents into an integrated mathematical model would lead to a better understanding of cardiomyocyte development. To simulate the action potential of the rodent ventricular cell at three representative developmental stages, quantitative changes in the ionic currents, pumps, exchangers, and sarcoplasmic reticulum (SR) Ca²⁺ kinetics were represented as relative activities, which were multiplied by conductance or conversion factors for individual ionic systems. The simulated action potential of the early embryonic ventricular cell model exhibited spontaneous activity, which ceased in the simulated action potential of the late embryonic and neonatal ventricular cell models. The simulations with our models were able to reproduce action potentials that were consistent with the reported characteristics of the cells in vitro. The action potential of rodent ventricular cells at different developmental stages can be reproduced with common sets of mathematical equations by multiplying conductance or conversion factors for ionic currents, pumps, exchangers, and SR Ca ²⁺ kinetics by relative activities. © Springer Science + Business Media B.V. 2007.

关键词： Cardiac ventricular cell Computer modeling Development Electrophysiology Ion channels Spontaneous electrical activity

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Decision fusion of circulating markers for breast cancer detection in premenopausal women

Decision fusion of circulating markers for breast cancer det...

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7th IEEE International Conference on bioinformatics and Bioengineering, BIBE

作者： Jesneck, Jonathan L. Mukherjee, Sayan Nolte, Loren W. Lokshin, Anna E. Marks, Jeffrey R. Lo, Joseph Department of Biomedical Engineering Department of Statistical Science Computational Biology and Bioinformatics Program Duke Advanced Imaging Labs. Institute for Genome Sciences and Policy Department of Computer Science Duke University Department of Electrical and Computer Engineering Division of Hematology/Oncology University of Pittsburgh School of Medicine University of Pittsburgh Cancer Institute Pittsburgh PA 15213 United States Department of Experimental Surgery Duke University Medical Center Medical Physics Graduate Program Duke University Durham NC 27708 United States

ISBN: (纸本)1424415098

Current mammographic screeningfor breast cancer is less effective for younger women. To complement mammography for premenopausal women, we investigated the feasibility screening test using 98 blood serum proteins. Because the data set was very noisy and contained only weak features, we used a classifier designed for noisy data: decision fusion. Decision fusion outperformed both a support vector machine (SVM) and linear regression with forward stepwise feature selection on all three two-class classification tasks: normal tissue vs. cancer, normal tissue vs. benign lesions, and benign lesions vs. cancer. Decision fusion detected cancer moderately well (AUC=0.84 on normal vs. cancer), demonstrating promise as a screening tool. Decision fusion also detected benign lesions similarly well (AUC=0.83 on normal vs. benign lesions) and was the only classifier to achieve any success in separating benign from malignant lesions (AUC=0.64 on benign vs. cancer). The classification results suggest that the assayed proteins are more indicative of a secondary effect, such as immune response, rather than specific for breast cancer. In conclusion, the decision fusion classifier demonstrated some promise in detecting breast lesions and outperformed other classifiers, especially for the very noisy classification problem of distinguishing benign from malignant lesions. ©2007 IEEE.

关键词： Tissue

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