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8th International Conference on bioinformatics: Computational Biology, InCoB 2009

作者： Rhee, Je-Keun Joung, Je-Gun Chang, Jeong-Ho Fei, Zhangjun Zhang, Byoung-Tak Graduate Program in Bioinformatics Seoul National University Seoul 151-744 Korea Republic of Seoul National University Seoul 151-744 Korea Republic of Boyce Thompson Institute for Plant Research Cornell University Ithaca NY 14853 United States Konan Technology Inc. Seoul 135-080 Korea Republic of USDA Robert W. Holley Center for Agriculture and Health Ithaca NY 14853 United States School of Computer Science and Engineering Seoul National University Seoul 151-744 Korea Republic of

Background: Gene regulation is a key mechanism in higher eukaryotic cellular processes. One of the major challenges in gene regulation studies is to identify regulators affecting the expression of their target genes in specific biological processes. Despite their importance, regulators involved in diverse biological processes still remain largely unrevealed. In the present study, we propose a kernel-based approach to efficiently identify core regulatory elements involved in specific biological processes using gene expression profiles. Results: We developed a framework that can detect correlations between gene expression profiles and the upstream sequences on the basis of the kernel canonical correlation analysis (kernel CCA). Using a yeast cell cycle dataset, we demonstrated that upstream sequence patterns were closely related to gene expression profiles based on the canonical correlation scores obtained by measuring the correlation between them. Our results showed that the cell cycle-specific regulatory motifs could be found successfully based on the motif weights derived through kernel CCA. Furthermore, we identified co-regulatory motif pairs using the same framework. Conclusion: Given expression profiles, our method was able to identify regulatory motifs involved in specific biological processes. The method could be applied to the elucidation of the unknown regulatory mechanisms associated with complex gene regulatory processes. © 2012 BioMed Central Ltd .

关键词： Gene expression

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Evolution of olfactory receptor genes in East Asian loaches

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Zoological Studies 2009年第2期48卷 223-237页

作者： Wang, Daryi Wang, Tzi-Yuan Weng, Li-Chuan Emori, Yasufumi Tzeng, Chyng-Shyan Li, Wen-Hsiung Biodiversity Research Center Academia Sinica Taipei 115 Taiwan Genomics Research Center Academia Sinica Taipei 115 Taiwan Department of Biophysics and Biochemistry Graduate School of Science University of Tokyo Bunkyo Tokyo 113-0033 7-3-1 Hongo Japan Undergraduate Program for Bioinformatics and System Biology University of Tokyo Bunkyo Tokyo 113-0033 7-3-1 Hongo Japan Institute of Bioinformatics and Structural Biology Department of Life Sciences National Tsing Hua University Hsinchu 300 Taiwan

Daryi Wang, Tzi-Yuan Wang, Li-Chuan Weng, Yasufumi Emori, Chyng-Shyan Tzeng, and Wen-Hsiung Li (2009) Evolution of olfactory receptor genes in East Asian loaches. Zoological Studies 48(2): 223-237. It is well known that fish have fewer olfactory receptor (OR) genes than mammals do. In order to investigate the divergence of and evolutionary changes in OR genes in fish, 2 loach OR gene families (D1/3 and D32) from Taiwanese and Chinese populations of 2 species (Misgurnus anguillicaudatus and Paramisgurnus dabryanus) were analyzed. We found duplications in both D1/3 and D32 that had accumulated after the separation of the island of Taiwan from the Asian mainland ~5 million yrs ago. The accumulation of duplicate copies in a relatively short time suggests that gaining extra copies of OR genes may have been selectively advantageous for adapting to local environments. On the other hand, the loss of some OR genes in the 2 species in Taiwan may reflect loss of selective constraints on some OR genes. Moreover, unlike the situation in mammals in which pseudogenes are found in each family, pseudogenes are clustered in an expanding gene family in P. dabryanus in Taiwan. The presence of pseudogenes and the limited number of functional OR genes in fish suggest that fish do not need a large number of OR genes. Finally, the dynamic changes in OR gene number and the possible explanation for a lower OR gene number in fish are discussed. http://***/Journals/48.2/***.

关键词： Adaptation Misgurnus anguillicaudatus Multigene family Olfaction Paramisgurnus dabryanus

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Comprehensive analysis of the pseudogenes of glycolytic enzymes in vertebrates: The anomalously high number of GAPDH pseudogenes highlights a recent burst of retrotrans-positional activity

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BMC Genomics 2009年第1期10卷 480-480页

作者： Liu, Yuen-Jong Zheng, Deyou Balasubramanian, Suganthi Carriero, Nicholas Khurana, Ekta Robilotto, Rebecca Gerstein, Mark B. Department of Surgery Beth Israel Deaconess Medical Center Harvard Medical School Boston MA 110 Francis Street United States Department of Molecular Biophysics and Biochemistry Yale University New Haven CT 06520 P.O. Box 208114 United States Albert Einstein College of Medicine of Yeshiva University Department of Neurology Rose F. Kennedy Center Bronx NY 10461 1410 Pelham Parkway South United States Program in Computational Biology and Bioinformatics Yale University New Haven CT 06520 United States Department of Computer Science Yale University New Haven CT 06520 Bass 432 266 Whitney Avenue United States

Background: Pseudogenes provide a record of the molecular evolution of genes. As glycolysis is such a highly conserved and fundamental metabolic pathway, the pseudogenes of glycolytic enzymes comprise a standardized genomic measuring stick and an ideal platform for studying molecular evolution. One of the glycolytic enzymes, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), has already been noted to have one of the largest numbers of associated pseudogenes, among all proteins. Results: We assembled the first comprehensive catalog of the processed and duplicated pseudogenes of glycolytic enzymes in many vertebrate model-organism genomes, including human, chimpanzee, mouse, rat, chicken, zebrafish, pufferfish, fruitfly, and worm (available at http://***/glycolysis/). We found that glycolytic pseudogenes are predominantly processed, i.e. retrotransposed from the mRNA of their parent genes. Although each glycolytic enzyme plays a unique role, GAPDH has by far the most pseudogenes, perhaps reflecting its large number of non-glycolytic functions or its possession of a particularly retrotranspositionally active sub-sequence. Furthermore, the number of GAPDH pseudogenes varies significantly among the genomes we studied: none in zebrafish, pufferfish, fruitfly, and worm, 1 in chicken, 50 in chimpanzee, 62 in human, 331 in mouse, and 364 in rat. Next, we developed a simple method of identifying conserved syntenic blocks (consistently applicable to the wide range of organisms in the study) by using orthologous genes as anchors delimiting a conserved block between a pair of genomes. This approach showed that few glycolytic pseudogenes are shared between primate and rodent lineages. Finally, by estimating pseudogene ages using Kimura's two-parameter model of nucleotide substitution, we found evidence for bursts of retrotranspositional activity approximately 42, 36, and 26 million years ago in the human, mouse, and rat lineages, respectively. Conclusion: Overall, we pe

关键词： Glycolytic Enzyme Segmental Duplication Chimpanzee Genome Assembly Version ENSEMBL Release

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It takes glue to tango: MeDICi integration framework's data-intensive computing pipeline

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Scientific Computing 2008年第7期25卷 16-19页

作者： Gorton, Ian Oehmen, Christopher S. McDermott, Hason E. PNNL's Data Intensive Computing Program United States Laboratory's Bioinformatics and Computational Biology Group Fundamental and Computational Sciences Directorate United States

Researchers at the Department of Energy's (DOE) Pacific Northwest National Laboratory (PNNL) in Richland, WA, are creating computing environments for biologists that seamlessly integrate collections of data and computational resources. MeDICi is an evolving middleware platform for building complex, high-performance analytical applications. MIF components are constructed using Java programming interfaces that support inter-component communication using asynchronous messaging. Local components execute inside the MIF container. Remote components create distributed solutions and integrate with non-Java code. Mule provides the MIF container environment. MIF extends the Mule interface to make component and pipeline construction easier and to create an encapsulation device for component creation. The MIF interface is agnostic of the underlying Java messaging platform. This allows deployments to configure MIF applications using technologies that meet individual quality-of-service requirements.

关键词： Containers

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On codeword design in metric DNA spaces

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Natural Computing 2008年第3期8卷 571-588页

作者： Vinhthuy Phan Max H. Garzon Department of Computer Science and the Bioinformatics Program University of Memphis Memphis USA

Finding a large set of single DNA strands that do not crosshybridize to themselves and/or to their complements is an important problem in DNA computing, self-assembly, and DNA memories. We describe a theoretical framework to analyze this problem, gauge its computational difficulty, and provide nearly optimal solutions. In this framework, codeword design is reduced to finding large sets of strands maximaly separated in a DNA space and the size of such sets depends on the geometry of these metric spaces. We show that codeword design is NP-complete using any single reasonable measure that approximates the Gibbs energy, thus practically excluding the possibility of finding any procedure to find maximal sets efficiently. Second, we extend a technique known as shuffling to provide a construction that yields provably nearly-maximal codes. Third, we propose a filtering process that removes strands creating pairs with low Gibbs energies, as approximated by the nearest-neighbor model. These two steps produce large codes of thermodynamic high quality. The proposed framework can be used to gain an understanding of the Gibbs energy landscapes for DNA strands on which much of DNA computing and self-assembly are based.

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Glycans on influenza hemagglutinin affect receptor binding and immune response

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Proceedings of the National Academy of Sciences of the United States of America 2009年第43期106卷 18137-18142页

作者： Wang, Cheng-Chi Chen, Juine-Ruey Tseng, Yung-Chieh Hsu, Che-Hsiung Hung, Yu-Fu Chen, Shih-Wei Chen, Chin-Mei Khoo, Kay-Hooi Cheng, Ting-Jen Cheng, Yih-Shyun E. Jan, Jia-Tsrong Wu, Chung-Yi Ma, Che Wong, Chi-Huey Genomics Research Center Taipei 115 Taiwan Institute of Biochemical Sciences National Taiwan University Taipei 106 Taiwan Institute of Biochemistry and Molecular Biology National Yang-Ming University Taipei 112 Taiwan Chemical Biology and Molecular Biophysics Taiwan International Graduate Program Taipei 115 Taiwan Institute of Bioinformatics and Structural Biology National Tsing Hua University Hsinchu 300 Taiwan Institute of Biological Chemistry Academia Sinica Taipei 115 Taiwan

Recent cases of avian influenza H5N1 and the swine-origin 2009 H1N1 have caused a great concern that a global disaster like the 1918 influenza pandemic may occur again. Viral transmission begins with a critical interaction between hemagglutinin (HA) glycoprotein, which is on the viral coat of influenza, and sialic acid (SA) containing glycans, which are on the host cell surface. To elucidate the role of HA glycosylation in this important interaction, various defined HA glycoforms were prepared, and their binding affinity and specificity were studied by using a synthetic SA microarray. Truncation of the N-glycan structures on HA increased SA binding affinities while decreasing specificity toward disparate SA ligands. The contribution of each monosaccharide and sulfate group within SA ligand structures to HA binding energy was quantitatively dissected. It was found that the sulfate group adds nearly 100-fold (2.04 kcal/mol) in binding energy to fully glycosylated HA, and so does the biantennary glycan to the monoglycosylated HA glycoform. Antibodies raised against HA protein bearing only a single N-linked GlcNAc at each glycosylation site showed better binding affinity and neutralization activity against influenza subtypes than the fully glycosylated HAs elicited. Thus, removal of structurally nonessential glycans on viral surface glycoproteins may be a very effective and general approach for vaccine design against influenza and other human viruses.

关键词： Flu vaccine Glycan binding Glycosylation

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Microfluidic assembly blocks

Microfluidic assembly blocks

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12th International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2008

作者： Rhee, Minsoung Burns, Mark A. Department of Chemical Engineering University of Michigan United States Bioinformatics Program University of Michigan United States Department of Biomedical Engineering University of Michigan United States

The use of microfluidic systems in the life sciences is still limited due to the high-level fabrication expertise required for construction. A novel assembly approach for microdevice construction is presented. This approach involves prefabrication of in-dividual "microfluidic assembly blocks" in PDMS that can be readily assembled on plain glass slides to form microfluidic systems in minutes by non-expert users. We describe the prefabrication of various blocks and the hermetic assembly of microflui-dic devices using the MAB methodology. Finally, we demonstrate common micro-fluidic applications including laminar flow development, valve control, and cell cul-ture. © 2008 CBMS.

关键词： Fabrication

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Grappling with the Gulf

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Science 2009年第5911期323卷 210页

作者： Dov Greenbaum Mark Gerstein Mcdermott Will and Emory LLP 3150 Porter Drive Palo Alto CA 94304 USA. Department of Molecular Biophysics and Biochemistry Program in Computational Biology and Bioinformatics and Department of Computer Science Yale University New Haven CT 06520 USA.

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Mining knowledge for the methylation status of CpG islands using alternating decision trees

Mining knowledge for the methylation status of CpG islands u...

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Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC)

作者： Matthew B. Carson Robert Langlois Hui Lu Bioinformatics Program Department of Bioengineering University of Illinois Chicago IL USA

CpG island (CpGI) methylation is an epigenetic modification that occurs in eukaryotes and is based on the addition of a methyl group to the number 5 carbon of the pyrimidine ring of cytosine. When methylation of a CpGI occurs, the associated gene (if any) is not expressed [1]. Aberrant methylation is thought to be a causative agent in disease [2] and drug sensitivity [3], [4]. In this work, we have predicted the methylation status of CpGIs in human chromosome 21 using sequence patterns. These patterns showed a significantly different distribution between methylated and unmethylated islands in a previous work [5]. Using C4.5 with bagging and cost-sensitive learning, we achieved 85.6% accuracy, 82.8% sensitivity, and 86.4% specificity. We then constructed 1000 alternating decision trees using a bootstrapping method and analyzed the nodes that were conserved between the trees. This allowed us to find specific combinations of sequence patterns that distinguished between methylated and unmethylated CpGIs. Analysis of these characteristics offers certain insight into the conditions that permit or prevent methylation.

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Investigating the genomic basis of metabolic robustness through in silico flux analysis

Investigating the genomic basis of metabolic robustness thro...

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IEEE Conference on Decision and Control

作者： Marcin Imielinski Niels Klitgord Calin Belta N. Klitgord C. Belta University of Pennsylvania School of Medicine Philadelphia PA USA Boston University Graduate Program in Bioinformatics Boston MA USA Boston University Graduate Program in Bioinformatics MA 02115 USA

ISBN: (纸本)9781424431236

We employ a novel implementation of flux balance analysis to investigate the role of genome structure in the maintenance of metabolic robustness. We propose the hypothesis that the genomic organization of a bacterium buffers its metabolome against random gene deletion. To test this hypothesis, we use a novel implementation of producibility analysis to determine the metabolomic impact of gene deletions in the E. coli iJR904 genome-scale metabolic model. From these results, we determine metabolomic fragility, which we compute as the average number of metabolites knocked out across all gene deletions of a given size in a given nutrient media. We apply this analysis for three deletion window sizes (4000, 8000, 16000 bp) across the length of the E. coli genome. We compare these results to those obtained from several null distributions of permuted genomes to assess the impact of E. coli genome organization on its metabolic robustness. Our results strongly suggest that the arrangement of genes on the E. coli genome buffers metabolite producibility against random gene deletion. Our results have interesting implications for the understanding of metabolic network evolution. Future work includes examining our hypothesis for a wider range of deletion sizes and nutrient environments and extending our results to the metabolic networks of other species.

关键词： Genomics bioinformatics Robustness Biochemistry Metabolomics Biological system modeling Organisms Robust control Testing Biological systems

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