ABSTRACT
We have combined and compared three techniques for predicting functional interactions based on comparative genomics (methods based on conserved operons, protein fusions and correlated evolution) and optimized these methods to predict coregulated sets of genes in 24 complete genomes, including Saccharomyces cerevisiae, Caenorhabditis elegans and 22 prokaryotes. The method based on conserved operons was the most useful for this purpose. Upstream regions of the genes comprising these predicted regulons were then used to search for regulatory motifs in 22 prokaryotic genomes using the motif-discovery program AlignACE. Many significant upstream motifs, including five known Escherichia coli regulatory motifs, were identified in this manner. The presence of a significant regulatory motif was used to refine the members of the predicted regulons to generate a final set of predicted regulons that share significant regulatory elements.
Subject(s)
Genome , Regulatory Sequences, Nucleic Acid/genetics , Regulon/genetics , Animals , Base Sequence , Caenorhabditis elegans/genetics , Caenorhabditis elegans/metabolism , Computational Biology , Databases, Factual , Escherichia coli/genetics , Escherichia coli/metabolism , Genes/genetics , Phylogeny , Prokaryotic Cells/metabolism , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae/metabolism , Sequence AlignmentABSTRACT
Physiological models of transmitral flow predict E-wave contour alteration in response to variation of model parameters (stiffness, relaxation, mass) reflecting the physiology of hypertension. Accordingly, analysis of only the E-wave (rather than the E-to-A ratio) should be able to differentiate between hypertensive subjects and control subjects. Conventional versus model-based image processing methods have never been compared in their ability to differentiate E-waves of hypertensive subjects with respect to age-matched control subjects. Digitally acquired transmitral Doppler flow images were analyzed by an automated model-based image processing method. Model-derived indexes were compared with conventional E-wave indexes in 22 subjects: 11 with hypertension and echocardiographically verified ventricular hypertrophy and 11 age-matched nonhypertensive control subjects. Conventional E-wave indexes included peak E, E, and acceleration and deceleration times. Model-based image processing-derived indexes included acceleration and deceleration times, potential energy index, and damping and kinematic constants. Intergroup comparison yielded lower probability values for model-based compared with conventional indexes. In the subjects studied, Doppler E-wave images analyzed by this automated method (which eliminates the need for hand-digitizing contours or the manual placement of cursors) demonstrate diastolic function alteration secondary to hypertension made discernible by model-based indexes. The method uses the entire E-wave contour, quantitatively differentiates between hypertensive subjects and control subjects, and has potential for automated noninvasive diastolic function evaluation in large patient populations, such as hypertension and other transmitral flow velocity-altering pathophysiological states.
