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Biomedical subjects

Vladimir Pavlovic

Publications and source records attributed to Vladimir Pavlovic.

6 recordsLinked to original sources

Protein classification using probabilistic chain graphs and the Gene Ontology structure.

MOTIVATION: Probabilistic graphical models have been developed in the past for the task of protein classification. In many cases, classifications obtained from the Gene Ontology have been used to validate these models. In this work we directly incorporate the structure of the Gene Ontology into the graphical representation for protein classification. We present a method in which each protein is represented by a replicate of the Gene Ontology structure, effectively modeling each protein in its own 'annotation space'. Proteins are also connected to one another according to different measures of functional similarity, after which belief propagation is run to make predictions at all ontology terms. RESULTS: The proposed method was evaluated on a set of 4879 proteins from the Saccharomyces Genome Database whose interactions were also recorded in the GRID project. Results indicate that direct utilization of the Gene Ontology improves predictive ability, outperforming traditional models that do not take advantage of dependencies among functional terms. Average increase in accuracy (precision) of positive and negative term predictions of 27.8% (2.0%) over three different similarity measures and three subontologies was observed. AVAILABILITY: C/C++/Perl implementation is available from authors upon request.

Algorithms↗

Differentiation of human umbilical cord blood CD133+ stem cells towards myelo-monocytic lineage.

BACKGROUND: Characterisation of stem cells by flow cytometry, their expansion and differentiation are presently of major interest for cell engineering as the basis of a therapeutic concept for transplantation. Haematopoietic stem cells (HSC) express CD34, the adhesion structure which binds 2L-selectin, CD117, a receptor for stem cell factor (SCF; c-kit ligand), and CD133, a transmembrane protein belonging to the family of mucoproteins. METHODS: The aim of the present investigation was the systematic investigation of proliferation and differentiation characteristics of umbilical cord blood stem cells (UCBSC) isolated by an immmunomagnetic separation system using CD133 antibody-coated microbeads and to evaluate the effects of different sera and various concentrations, as well as the effects of IL-3 and IL-6 on total cell expansion and differentiation of isolated CD133+ cells. Differentiation patterns were measured by flow cytometry. RESULTS: After the immmunomagnetic separation the yield of CD133+ cells was 0.45+/-0.17 x 10(6) cells/ml; the purity of isolated CD133+ cells was 95.79+/-1.86%. The majority of CD133+ cells coexpressed CD117. The most pronounced expansion during cultivation of 2 weeks was achieved in media supplemented with 12.5% horse serum plus 12.5% fetal calf serum (FCS) with stem cell factor and interleukine 3; the fold-expansion was 16.67+/-6.20. During the cultivation period, UCBSC were constantly loosing stem cell markers and differentiated towards myelo-monocyte lineage (granulocytes and/or monocytes). CONCLUSIONS: These in vitro results demonstrate that thorough investigation of various cultivation conditions is needed for successful expansion and differentiation of stem cells towards different lineages to be used therapeutically for replacement of damaged cells.

AC133 Antigen↗

RankGene: identification of diagnostic genes based on expression data.

RankGene is a program for analyzing gene expression data and computing diagnostic genes based on their predictive power in distinguishing between different types of samples. The program integrates into one system a variety of popular ranking criteria, ranging from the traditional t-statistic to one-dimensional support vector machines. This flexibility makes RankGene a useful tool in gene expression analysis and feature selection.

Algorithms↗

Human-mouse gene identification by comparative evidence integration and evolutionary analysis.

The identification of genes in the human genome remains a challenge, as the actual predictions appear to disagree tremendously and vary dramatically on the basis of the specific gene-finding methodology used. Because the pattern of conservation in coding regions is expected to be different from intronic or intergenic regions, a comparative computational analysis can lead, in principle, to an improved computational identification of genes in the human genome by using a reference, such as mouse genome. However, this comparative methodology critically depends on three important factors: (1) the selection of the most appropriate reference genome. In particular, it is not clear whether the mouse is at the correct evolutionary distance from the human to provide sufficiently distinctive conservation levels in different genomic regions, (2) the selection of comparative features that provide the most benefit to gene recognition, and (3) the selection of evidence integration architecture that effectively interprets the comparative features. We address the first question by a novel evolutionary analysis that allows us to explicitly correlate the performance of the gene recognition system with the evolutionary distance (time) between the two genomes. Our simulation results indicate that there is a wide range of reference genomes at different evolutionary time points that appear to deliver reasonable comparative prediction of human genes. In particular, the evolutionary time between human and mouse generally falls in the region of good performance; however, better accuracy might be achieved with a reference genome further than mouse. To address the second question, we propose several natural comparative measures of conservation for identifying exons and exon boundaries. Finally, we experiment with Bayesian networks for the integration of comparative and compositional evidence.

Animals↗

A comparative genomic method for computational identification of prokaryotic translation initiation sites.

The ever growing number of completely sequenced prokaryotic genomes facilitates cross-species comparisons by genomic annotation algorithms. This paper introduces a new probabilistic framework for comparative genomic analysis and demonstrates its utility in the context of improving the accuracy of prokaryotic gene start site detection. Our frame work employs a product hidden Markov model (PROD-HMM) with state architecture to model the species-specific trinucleotide frequency patterns in sequences immediately upstream and downstream of a translation start site and to detect the contrasting non-synonymous (amino acid changing) and synonymous (silent) substitution rates that differentiate prokaryotic coding from intergenic regions. Depending on the intricacy of the features modeled by the hidden state architecture, intergenic, regulatory, promoter and coding regions can be delimited by this method. The new system is evaluated using a preliminary set of orthologous Pyrococcus gene pairs, for which it demonstrates an improved accuracy of detection. Its robustness is confirmed by analysis with cross-validation of an experimentally verified set of Escherichia coli K-12 and Salmonella thyphimurium LT2 orthologs. The novel architecture has a number of attractive features that distinguish it from previous comparative models such as pair-HMMs.

Algorithms↗

Quantification of the influence of mycophenolic acid on the release of endothelial adhesion molecules.

BACKGROUND: Mycophenolic acid selectively inhibits inosine 5'-monophosphate dehydrogenase leading to a shortage of guanosine nucleotides. Since GTP is required for the synthesis of glycoproteins, this immunosuppressive drug also influences the production of several cell adhesion molecules. METHOD: Soluble endothelial cell adhesion molecules released into cell culture supernatants after an incubation period of 16 h are assessed via a standard ELISA procedure applying test kits for E-selectin, VCAM-1 and ICAM-1. RESULTS: Treatment with TNF-alpha leads to the induction of E-selectin and causes a significant increase in VCAM-1 and ICAM-1 content in the supernatant in relation to the level of unstimulated cells. Due to the inhibitory effects of MPA-applied either alone or in combination with cyclosporin A and prednisolone-sE-selectin is significantly reduced and sVCAM-1 is slightly but not significantly decreased, whereas sICAM-1 levels remain unchanged. CONCLUSIONS: We demonstrate that the influence of MPA on endothelial cell adhesion molecules can readily be determined via ELISA. The results indicate that the immunosuppression by MPA is also achieved by slightly reducing the expression and consequent release of E-selectin, a pivotal molecule in the first step of leucocyte-endothelial interactions.

Cell Adhesion Molecules↗