Frontiers of Bioinformatics Unsolved Problems and Challenges (2005) / Chapter Skim
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Poster Abstracts
Poster Abstracts
Pages 27-46
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FRONTIERS OF BIOINFORMATICS: UNSOLVED PROBLEMS AND CHALLENGES October 15-17, 2004 POSTER ABSTRACTS 27
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It is useful to obtain a global picture of all the ways the viral population could respond to the current drug treatment. To address this problem, we have developed a conditional selection pressure (Ka/Ks)
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These simulations will be analyzed in a broader context in order to determine general dynamic properties of amino acids and proteins in water. We are calling this effort molecular dynameomics.
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Then, by comparing the word counts between these two sets of exons, and their neighboring introns, we find motifs that are associated with alternative splicing and are potential regulators. In particular, we find that adjacent introns of alternatively spliced exons are A/T rich, while those from constitutively spliced exons are G/C rich.
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Structure base methods are less sensitive to sequence similarity, but many of the structure based methods require manual creation of models and are thus limited by the number of available functional models. Methods for function annotation at a structural-genomics scale will require both greater sensitivity than what sequence only methods provide and more functional models than what the structural models offer.
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With the recent increase of the estimates of the number of human genes that undergoes alternative splicing from 5% to 74%, it becomes critical to develop a better understanding of its functional consequences and regulatory mechanisms. We conducted a large scale study of the distribution of protein domains in a curated data set of several thousand genes and identified protein domains disproportionately distributed among alternatively spliced genes.
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* Joint Center for Structural Genomics, Stanford Synchrotron Radiation Laboratory, SLAC, Department of Computer Science, Stanford University Rapid protein structure determination relies greatly on software that can automatically build a protein model into an experimental electron density map.
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Spormann2 and Samuel Karlin1 1 Department of Mathematics and Departments of Civil and Environmental Engineering, of 2 Biological Sciences, and of Geological and Environmental Sciences, Stanford University Highly expressed genes in most unicellular and some multicellular organisms exhibit characteristic codon usage biases that distinguish them from the bulk of genes in a genome. We have developed a method to identify predicted highly expressed (PHX)
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For example, it is used to find conserved DNA motifs in the upstream sequences of co-expressed genes from microarray and chromatin immunoprecipitation (CHIP) experiments.
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Reyes Whole Proteome Functional Annotation via Automated Detection of Ligand 3-D Binding Site Motifs: Application to ATP- and GTP-Binding Sites in Unannotated Proteins of Dictyostelium discoideum Vicente M Reyes University of California, San Diego The first few years of the new millennium have seen the avalanche of genome sequence data, a trend that is predicted to continue for the next 10 to 15 years.
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discoideum were then chosen as the pilot test set. Two binding site motifs were deduced from the ser/thr PK training set, one with the two ribose hydroxyls "bound" to a single protein residue centroid (type 1)
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Poster Abstract 11) Serge Saxonov SampleScan: A Sampling Approach to Motif Discovery in Nucleotide Sequences Serge Saxonov, Serafim Batzoglou, Douglas L Brutlag Stanford University When looking for DNA motifs on a genomic scale one is faced with two main challenges.
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Currently there is no good agreement among different assignment methods for what constitute the basic structural unit, underscoring the complexity of structural domain assignment. This work discusses tendencies of individual methods and highlights the problematic areas in assignment of structural domains by experts as well as by fully automated methods.
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Xu, Y 2003 Improving the Performance of DomainParser for Structural Domain Partition Using Neural Network, Nucleic Acids Res.31(3)
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We present a simple and general approach for distinguishing changes in alternative splicing from changes inexpression, based on detecting systematic anti-correlation between two different samples' log ratios versus a pool containing both samples. We have tested this analysis method on microarray data for five human tissues, generated using a standard microarray platform and experimental protocols previously shown to be sensitive to alternative splicing.
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Alternatively spliced regions undergo relaxed purifying selection pressure compared to other portions of the gene. Our data suggest that alternative splicing is able to open neutral paths for evolution, a principle that can add significantly to current theory of molecular evolution.
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Simple significance tests and clustering methods have provided us with an initial filtering of NCS based on the functional annotation and experimental information. These results provide a promising first set of NCS examples for further exploration.
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In some cases our ontology allowed us to propose novel localizations using simple logical rules. Our cellular architecture ontology contains links to the Gene Ontology (GO)
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Population structure remains a challenging issue producing spurious associations between genotype and phenotype. This study demonstrates the promise of using LD mapping to study the genetic basis of complex traits and potentially genomewide disease association.
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