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Integrating Prior Knowledge into the Fitness Function of an Evolutionary Algorithm for Deriving Gene Regulatory NetworksBirkmeier, Bettina January 2006 (has links)
The topic of gene regulation is a major research area in the bioinformatics community. In this thesis prior knowledge from Gene Ontology in the form of templates is integrated into the fitness function of an evolutionary algorithm to predict gene regulatory networks. The resulting multi-objective fitness functions are then tested with MAPK network data taken from KEGG to evaluate their respective performances. The results are presented and analyzed. However, a clear tendency cannot be observed. The results are nevertheless promising and can provide motivation for further research in that direction. Therefore different ideas and approaches are suggested for future work.
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Rapid membrane protein topology predictionHennerdal, Aron, Elofsson, Arne January 2011 (has links)
State-of-the-art methods for topology of α-helical membrane proteins are based on the use of time-consuming multiple sequence alignments obtained from PSI-BLAST or other sources. Here, we examine if it is possible to use the consensus of topology prediction methods that are based on single sequences to obtain a similar accuracy as the more accurate multiple sequence-based methods. Here, we show that TOPCONS-single performs better than any of the other topology prediction methods tested here, but ~6% worse than the best method that is utilizing multiple sequence alignments. AVAILABILITY AND IMPLEMENTATION: TOPCONS-single is available as a web server from http://single.topcons.net/ and is also included for local installation from the web site. In addition, consensus-based topology predictions for the entire international protein index (IPI) is available from the web server and will be updated at regular intervals.
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An Analysis of the Expression, Regulation and Interaction of Genes and Gene Products using Computational and Molecular MethodsAmmar, Ron 30 July 2008 (has links)
Bioinformatic methods were applied to address biological questions. Two new eFP browser web
tools were constructed for the intuitive visualization of data from large-scale data sets. In
addition, a predicted interactome was constructed for Arabidopsis thaliana and validated using a
gene coexpression analysis. The Arabidopsis Interactions Viewer was created to enable access to
and visualization of predicted and confirmed interactions in the Arabidopsis interactome.
In a separate analysis short sequence matches were identified between introns and coding
sequences in several model systems including Arabidopsis, human, C. elegans and 12 Drosophila
species. Several hundred to thousands of matches were found near each other in terms of
chromosomal location, and were termed Proximal Intron N-mer (PIN) matches. Sequence
matches were conserved between 11 Drosophila species and D. melanogaster, suggesting a
potential functional role. Novel plasmids were designed to test whether PIN matches are
functional in vivo.
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An Analysis of the Expression, Regulation and Interaction of Genes and Gene Products using Computational and Molecular MethodsAmmar, Ron 30 July 2008 (has links)
Bioinformatic methods were applied to address biological questions. Two new eFP browser web
tools were constructed for the intuitive visualization of data from large-scale data sets. In
addition, a predicted interactome was constructed for Arabidopsis thaliana and validated using a
gene coexpression analysis. The Arabidopsis Interactions Viewer was created to enable access to
and visualization of predicted and confirmed interactions in the Arabidopsis interactome.
In a separate analysis short sequence matches were identified between introns and coding
sequences in several model systems including Arabidopsis, human, C. elegans and 12 Drosophila
species. Several hundred to thousands of matches were found near each other in terms of
chromosomal location, and were termed Proximal Intron N-mer (PIN) matches. Sequence
matches were conserved between 11 Drosophila species and D. melanogaster, suggesting a
potential functional role. Novel plasmids were designed to test whether PIN matches are
functional in vivo.
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Molecular basis of gene dosage sensitivityJanuary 2009 (has links)
Deviation of gene expression from normal levels has been associated with diseases. Both under- and overexpression of genes could lead to deleterious biological consequences. Dosage balance has been proposed to be a key issue of determining gene expression phenotype. Gene deletion or overexpression of any component in a protein complex produces abnormal phenotypes. As a result, interacting partners should be co-expressed to avoid dosage imbalance effects. The strength of transcriptional co-regulation of interacting partners is supposed to reflect gene dosage sensitivity. Although many cases of dosage imbalance effects have been reported, the molecular attributes determining dosage sensitivity remain unknown. This thesis uses a protein structure analysis protocol to explore the molecular basis of gene dosage sensitivity, and studies the post-transcriptional regulation of dosage sensitive genes.
Solvent-exposed backbone hydrogen bond (SEBH or called as dehydron) provides a structure marker for protein interaction. Protein structure vulnerability, defined as the ratio of SEBHs to the overall number of backbone hydrogen bonds, quantifies the extent to which protein relies on its binding partners to maintain structure integrity. Genes encoding vulnerable proteins need to be highly co-expressed with their interacting partners. Protein structure vulnerability may hence serves as a structure marker for dosage sensitivity. This hypothesis is examined through the integration of gene expression, protein structure and interaction data sets. Both gene co-expression and protein structure vulnerability are calculated for each interacting subunits from human and yeast complexes. It turns out that structure vulnerability quantifies dosage sensitivity for both temporal phases (yeast) and tissue-specific (human) patterns of mRNA expression, determining the extent of co-expression similarity of binding partners.
Highly dosage sensitive genes encode proteins which are vulnerable to water attack. They are subject to tight post-transcriptional regulation. In human, this extra regulation is achieved through extensive microRNA targeting of genes coding for extremely vulnerable proteins. In yeast, on the other hand, our results imply that such a regulation is likely achieved through sequestration of the extremely vulnerable proteins into aggregated states. The 85 genes encoding extremely vulnerable proteins contain the five confirmed yeast prions. It has been proposed that yeast prion protein aggregation could produce multiple phenotypes important for cell survival in some particular circumstances. These results suggest that extremely vulnerable proteins resorting to aggregation to buffer the deleterious consequences of dosage imbalance. However, a rigorous proof will require a structure-based integration of information drawn from the interactome, transcriptome and post-transcriptional regulome.
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Tarfetpf: A Plasmodium faciparum protein localization predictorRao, Aditya January 2004 (has links)
No description available.
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Modeling Cancer Progression on the Pathway LevelEdelman, Elena Jane 11 December 2008 (has links)
<p>Over the past several decades, many genes have been discovered that govern important functions in the development of a variety of different cancers. However, biological insight from the list of genes is still limited and the underlying mechanisms that occur in the cell during tumorigenesis have not been well established. Studying cancer progression in terms of the oncogenic pathways that are responsible for specific actions that change normal cells into tumors is a means for bringing insight onto these issues. The work presented here will uncover mechanisms that are occurring at the pathway level that first initiate tumor formation and then continue through cancer progression and finally metastasis. This knowledge will allow for drug treatment that is better targeted towards an individual.</p><p>Microarray technology has allowed for the collection of gene expression datasets from clinical cancer and other studies. These datasets can be used to study how expression levels of individual genes or groups of related genes are altered in individuals from different phenotypic groups. Statistical methods exist which assay pathway enrichment by phenotypic class but do not describe individual variation.
In order to study this individual variation, we developed a formal statistical method called ASSESS which measures the enrichment of a gene set in each sample in an expression dataset.</p><p>As cancer advances through the stages of initiation, progression, and proliferation, multiple pathways experience disruptions at various times. However, there is still much unknown on these particular pathways that evidence gene expression changes throughout tumorigenesis. Using gene expression datasets comprised of individuals
with tumors classified by location and stage, we applied ASSESS in order to study the data on the pathway level. We then utilized novel statistical methods to uncover the pathways that play a role in cancer progression and in what order the pathways become perturbed.</p><p>These analyses can give a basis for how genetic disruptions serve to alter actions in specific cell types. The results may provide insight that will lead to treatments of existing tumors and prevention of incipient cancers from forming. Treatments for existing tumors will use multiple drugs to target the pathways that show an altered state of activity.</p> / Dissertation
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The Geometry of CancerGuinney, Justin January 2009 (has links)
<p>Cancer is a complex, multifaceted disease that operates through dynamic changes in the genome. Cancer is best understood through the process that generates it -- random mutations operated on by natural selection -- and several global hallmarks that describe its broad mechanisms. While many genes, protein interactions, and pathways have been enumerated as a kind of ``parts'' list for cancer, researchers are attempting to synthesize broader models for inferring and predicting cancer behavior using high-throughput data and integrative analyses. </p><p>The focus of this thesis is on the development of two novel methods that are optimized for the analysis of complex cancer phenotypes. The first method incorporates ideas from gradient learning with multitask learning to assess statistical dependencies across multiple related data sets. The second method integrates multiscale analysis on graphs and manifolds developed in applied harmonic analysis with sparse factor models, a mainstay of applied statistics. This method generates multiscale factors that are used for inferring hierarchical associations within complex biological networks. The primary biological focus is the inference of gene and pathway dependencies associated with cancer progression and metastatic disease in prostate cancer. Significant findings include evidence of Skp2 degradation of the cell-cycle regulator p27, and the upstream deregulation of the TGF-beta pathway, driving prostate cancer recurrence.</p> / Dissertation
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Escherichia coli proteomics and bioinformaticsNiu, Lili 15 May 2009 (has links)
A lot of things happen to proteins when Escherichia coli cells enter stationary phase, such as protein amount, post-translational modifications, conformation changes, and component of protein complex. Proteomics, which study the whole component of proteins, can be used to study the products of the genome and the physiology of Escherichia coli cells at different conditions. By comparing proteome from different growth phases, such as exponential and stationary phase, a lot of proteins with changes can be identified at the same time, which provides a pilot for further studies of mechanism. Current global proteomic studies have identified about 27% of the annotated proteins of E. coli, most of which are predicted to be abundance proteins. Subproteomics, the study of specific subsets of the proteome, can be used to study specific functional classes of proteins and low abundance proteins. In this dissertation, using non-denatured anion exchange column with 2D SDS-PAGE and tandem mass spectrometry, difference of E. coli cells between exponential and stationary phase were studied for whole soluble proteome. Also, using heparin column and mass spectrometry with tandem mass spectrometry, heparin-binding proteins were identified and analyzed for exponential growth and stationary phases. To manage and display the data generated by proteomics, a web-based database has been constructed for experiments in E. coli proteomics (EEP), which includes NonDeLC, Heparome, AIX/2D PAGE and other proteomic studies.
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Bayesian learning in bioinformaticsGold, David L. 15 May 2009 (has links)
Life sciences research is advancing in breadth and scope, affecting many areas of life
including medical care and government policy. The field of Bioinformatics, in particular,
is growing very rapidly with the help of computer science, statistics, applied
mathematics, and engineering. New high-throughput technologies are making it possible
to measure genomic variation across phenotypes in organisms at costs that were
once inconceivable. In conjunction, and partly as a consequence, massive amounts
of information about the genomes of many organisms are becoming accessible in the
public domain. Some of the important and exciting questions in the post-genomics
era are how to integrate all of the information available from diverse sources.
Learning in complex systems biology requires that information be shared in a natural
and interpretable way, to integrate knowledge and data. The statistical sciences can
support the advancement of learning in Bioinformatics in many ways, not the least
of which is by developing methodologies that can support the synchronization of efforts
across sciences, offering real-time learning tools that can be shared across many
fields from basic science to the clinical applications. This research is an introduction
to several current research problems in Bioinformatics that addresses integration
of information, and discusses statistical methodologies from the Bayesian school of
thought that may be applied. Bayesian statistical methodologies are proposed to integrate biological knowledge and
improve statistical inference for three relevant Bioinformatics applications: gene expression
arrays, BAC and aCGH arrays, and real-time gene expression experiments.
A unified Bayesian model is proposed to perform detection of genes and gene classes,
defined from historical pathways, with gene expression arrays. A novel Bayesian statistical
method is proposed to infer chromosomal copy number aberrations in clinical
populations with BAC or aCGH experiments. A theoretical model is proposed, motivated
from historical work in mathematical biology, for inference with real-time gene
expression experiments, and fit with Bayesian methods. Simulation and case studies
show that Bayesian methodologies show great promise to improve the way we learn
with high-throughput Bioinformatics experiments.
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