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At least 379 records · Page 21Linked to original sources
PubMed1998

[Accuracy of computerized aid diagnosis, surgical simulation and facial appearance prediction in orthognathic surgery].

OBJECTIVE: The purpose of this report is to evaluated the accuracy and potential advantages of the computer system in orthognathic surgery. METHODS: The accuracy of computer prediction was evaluated in 31 patients by using the orthognathic surgery prediction expert system (OSPES) in the preoperative analysis, diagnosis, surgical simulation and preoperative facial appearance predication. RESULTS: This system could accurately predict the postoperative changing. The prediction accuracy for single-jaw surgery was over 95%; double-jaw 85%. The prediction for hard tissue was more accurate than that for soft tissue. CONCLUSION: The results of this study suggest that computer system is an acceptable tool for facial appearance prediction.

Computer Simulation↗
PubMed2003

The Z curve database: a graphic representation of genome sequences.

MOTIVATION: Genome projects for many prokaryotic and eukaryotic species have been completed and more new genome projects are being underway currently. The availability of a large number of genomic sequences for researchers creates a need to find graphic tools to study genomes in a perceivable form. The Z curve is one of such tools available for visualizing genomes. The Z curve is a unique three-dimensional curve representation for a given DNA sequence in the sense that each can be uniquely reconstructed given the other. The Z curve database for more than 1000 genomes have been established here. RESULTS: The database contains the Z curves for archaea, bacteria, eukaryota, organelles, phages, plasmids, viroids and viruses, whose genomic sequences are currently available. All the 3-dimensional Z curves and their three component curves are stored in the database. The applications of the Z curve database on comparative genomics, gene prediction, computation of G+C content with a windowless technique, prediction of replication origins and terminations of bacterial and archaeal genomes and study of local deviations from the Chargaff Parity Rule 2 etc. are presented in detail. The Z curve database reported here is a treasure trove in which biologists could find useful biological knowledge.

Animals↗
PubMed2001

From PREDs and open reading frames to cDNA isolation: revisiting the human chromosome 21 transcription map.

A supernumerary copy of human chromosome 21 (HC21) causes Down syndrome. To understand the molecular pathogenesis of Down syndrome, it is necessary to identify all HC21 genes. The first annotation of the sequence of 21q confirmed 127 genes, and predicted an additional 98 previously unknown "anonymous" genes (predictions (PREDs) and open reading frames (C21orfs)), which were foreseen by exon prediction programs and/or spliced expressed sequence tags. These putative gene models still need to be confirmed as bona fide transcripts. Here we report the characterization and expression pattern of the putative transcripts C21orf7, C21orf11, C21orf15, C21orf18, C21orf19, C21orf22, C21orf42, C21orf50, C21orf51, C21orf57, and C21orf58, the GC-rich sequence DNA-binding factor candidate GCFC (also known as C21orf66), PRED12, PRED31, PRED34, PRED44, PRED54, and PRED56. Our analysis showed that most of the C21orfs originally defined by matching spliced expressed sequence tags were correctly predicted, whereas many of the PREDs, defined solely by computer prediction, do not correspond to genuine genes. Four of the six PREDs were incorrectly predicted: PRED44 and C21orf11 are portions of the same transcript, PRED31 is a pseudogene, and PRED54 and PRED56 were wrongly predicted. In contrast, PRED12 (now called C21orf68) and PRED34 (C21orf63) are now confirmed transcripts. We identified three new genes, C21orf67, C21orf69, and C21orf70, not previously predicted by any programs. This revision of the HC21 transcriptome has consequences for the entire genome regarding the quality of previous annotations and the total number of transcripts. It also provides new candidates for genes involved in Down syndrome and other genetic disorders that map to HC21.

Animals↗
PubMed2002

Prediction of an HLA-DR-binding peptide derived from Wilms' tumour 1 protein and demonstration of in vitro immunogenicity of WT1(124-138)-pulsed dendritic cells generated according to an optimised protocol.

The Wilms' tumour 1 (WT1) protein is over-expressed in several types of cancer including leukaemias and might therefore constitute a novel target for immunotherapy. Recently, human leucocyte antigen (HLA) class I-binding WT1 peptides have been identified and shown to stimulate CD8(+) T cells in vitro. For maximal CD8 cell efficacy, CD4(+) helper T cells responding to major histocompatibility complex (MHC) class II-binding epitopes are required. Here, we report that scanning the WT1 protein sequence using an evidence-based predictive computer algorithm (SYFPEITHI) yielded a peptide WT1(124-138) predicted to bind the HLA-DRB1*0401 molecule with high affinity. Moreover, synthetic WT1(124-138)-peptide-pulsed dendritic cells (DC), generated according to a protocol optimised in the present study, sensitised T cells in vitro to proliferate and secrete interferon-gamma (IFN-gamma) when rechallenged with specific peptide-pulsed DC, but not with peripheral blood mononuclear cells (PBMC). These results suggest that the WT1 protein may yield epitopes immunogenic to CD4 as well as CD8 T cells, and therefore constitute a novel potential target for specific immunotherapy.

Algorithms↗
PubMed2006

Ortho effect in the Bergman cyclization: comparison of experimental approaches and dissection of cycloaromatization kinetics.

Four different experimental sources of kinetic information were combined to study the effect of ortho substituents on the rate of Bergman cycloaromatization. All methods confirm that the cyclization barrier is highly sensitive to the nature of the ortho substituents. However, the measured activation energies strongly depend on the choice of experimental technique: even the relative trends provided by the different methods agree with each other only in the case of acceptor substituents. Both the onset peaks and the activation energies determined by differential scanning calorimetry (DSC; either in neat enediynes or in their solutions in 10.6 M 1,4-cyclohexadiene (1,4-CHD)) strongly overestimate the reactivity of 1,2-diethynylbenzene, suggesting that DSC cannot be taken as a reliable indicator of enediyne reactivity. This discrepancy is likely to stem from the presence of side reactions with low activation barriers, especially important when the reaction is conducted in neat enediyne. On the other hand, kinetic measurements based on monitoring the concentrations of enediyne reactants and naphthalene products provide reliable general trends that include the parent benzannelated enediyne. These measurements confirm that both ortho-NO2 and ortho-CHO substituents substantially decrease activation energies for the Bergman cyclization, supporting earlier computational predictions. A comparison of theory and experiment suggests that computations at the Moeller-Plesset second-order perturbation theory (MP2)/6-31G level provide an excellent alternative to DFT when an accurate description of the contribution of noncovalent interactions to the activation energy is needed. Activation energies derived from k(eff), the effective rate constant under the pseudo-first-order approximation, depend on the 1,4-CHD concentrations. The true rate constant, k(1), for the cyclization step and the ratio of constants for the retro-Bergman ring opening, k(-1), and the intermolecular H-atom abstraction, k2, were determined from the dependence of cycloaromatization kinetics of ortho- and para-NO2 substituted enediynes on the concentration of 1,4-CHD.

Amino Acids, Cyclic↗
PubMed2006

Prediction of human microRNA targets.

MicroRNAs (miRNAs) are small, nonprotein-coding RNAs that regulate gene expression. Although hundreds of human miRNA genes have been discovered, the functions of most of these are unknown. Computational predictions indicate that miRNAs, which account for at least 1% of human protein-coding genes, regulate protein production for thousands of or possibly all of human genes. We discuss the functions of mammalian miRNAs and the experimental and computational methods used to detect and predict human miRNA target genes. Anticipating their impact on genome-wide discovery of miRNA targets, we describe the various computational tools and web-based resources available to predict miRNA targets.

3' Untranslated Regions↗
PubMed1977

Computer densitometry for angiographic assessment of arterial cholesterol content and gross pathology in human atherosclerosis.

Sequential change studies in human atherosclerosis are desirable in disease regression trials but are now limited by dependence on the occurrence of epidemiologic end-points. Prior radiographic studies have pertained to advanced obstructive atherosclerosis. This is a study of measures applied by computer-generated densitometry of angiograms to assess early to advanced nonobstructive atherosclerosis. Measures are based on pathologic and angiographic appearance of all stages of atherosclerosis and include image edge roughness, local width, and local contrast density changes. Femoral angiograms were made in 21 cadavers under simulated clinical conditions, with a pressurized radiopaque casting material. Full-size color photographs were made of 10 cm. segments of opened artery, with matching cast and arterial specimens analyzed for cholesterol content. Four graders, on two occasions, sequenced the photographs in increasing order of disease on the basis of the International Atherosclerosis Grading scheme. The correlation between the two sessions was 0.93. Thirteen computer indices correlated significantly with visual grade and cholesterol and were allowed to compete in a step-wise regression for best indices of prediction. Computer index correlation coefficient for visual grade prediction was 0.86, and for cholesterol content, 0.84. Computer densitometry measurement appears useful in the evaluation of all stages of atherosclerosis as recorded angiographically and obviates the necessity for exacting visual comparisons of large numbers of films.

Angiography↗
PubMedDate not supplied

A fully computational model for predicting percutaneous drug absorption.

The prediction of transdermal absorption for arbitrary penetrant structures has several important applications in the pharmaceutical industry. We propose a new data-driven, predictive model for skin permeability coefficients k(p) based on an ensemble model using k-nearest-neighbor models and ridge regression. The model was trained and validated with a newly assembled data set containing experimental data and structures for 110 compounds. On the basis of three purely computational descriptors (molecular weight, calculated octanol/water partition coefficient, and solvation free energy), we have developed a model allowing for the reliable, purely computational prediction of skin permeability coefficients. The model is both accurate and robust, as we showed in an extensive validation (correlation coefficient for leave-one-out cross validation: Q = 0.948, mean standard error: 0.2 for log k(p)).

Animals↗
PubMed2007

MODEL-molecular descriptor lab: a web-based server for computing structural and physicochemical features of compounds.

Molecular descriptors represent structural and physicochemical features of compounds. They have been extensively used for developing statistical models, such as quantitative structure activity relationship (QSAR) and artificial neural networks (NN), for computer prediction of the pharmacodynamic, pharmacokinetic, or toxicological properties of compounds from their structure. While computer programs have been developed for computing molecular descriptors, there is a lack of a freely accessible one. We have developed a web-based server, MODEL (Molecular Descriptor Lab), for computing a comprehensive set of 3,778 molecular descriptors, which is significantly more than the approximately 1,600 molecular descriptors computed by other software. Our computational algorithms have been extensively tested and the computed molecular descriptors have been used in a number of published works of statistical models for predicting variety of pharmacodynamic, pharmacokinetic, and toxicological properties of compounds. Several testing studies on the computed molecular descriptors are discussed. MODEL is accessible at http://jing.cz3.nus.edu.sg/cgi-bin/model/model.cgi free of charge for academic use.

Amino Acids↗
PubMed2000

RNA pseudoknot prediction in energy-based models.

RNA molecules are sequences of nucleotides that serve as more than mere intermediaries between DNA and proteins, e.g., as catalytic molecules. Computational prediction of RNA secondary structure is among the few structure prediction problems that can be solved satisfactorily in polynomial time. Most work has been done to predict structures that do not contain pseudoknots. Allowing pseudoknots introduces modeling and computational problems. In this paper we consider the problem of predicting RNA secondary structures with pseudoknots based on free energy minimization. We first give a brief comparison of energy-based methods for predicting RNA secondary structures with pseudoknots. We then prove that the general problem of predicting RNA secondary structures containing pseudoknots is NP complete for a large class of reasonable models of pseudoknots.

Algorithms↗
PubMed1998

Overexpression and topology of the Shigella flexneri O-antigen polymerase (Rfc/Wzy).

Lipopolysaccharides (LPS), particularly the O-antigen component, are one of many virulence determinants necessary for Shigella flexneri pathogenesis. O-antigen biosynthesis is determined mostly by genes located in the rfb region of the chromosome. The rfc/wzy gene encodes the O-antigen polymerase, an integral membrane protein, which polymerizes the O-antigen repeat units of the LPS. The wild-type rfc/wzy gene has no detectable ribosome-binding site (RBS) and four rare codons in the translation initiation region (TIR). Site-directed mutagenesis of the rare codons at positions 4, 9 and 23 to those corresponding to more abundant tRNAs and introduction of a RBS allowed detection of the rfc/wzy gene product via a T7 promoter/polymerase expression assay. Complementation studies using the rfc/wzy constructs allowed visualization of a novel LPS with unregulated O-antigen chain length distribution, and a modal chain length could be restored by supplying the gene for the O-antigen chain length regulator (Rol/Wzz) on a low-copy-number plasmid. This suggests that the O-antigen chain length distribution is determined by both Rfc/Wzy and Rol/Wzz proteins. The effect on translation of mutating the rare codons was determined using an Rfc::PhoA fusion protein as a reporter. Alkaline phosphatase enzyme assays showed an approximately twofold increase in expression when three of the rare codons were mutated. Analysis of the Rfc/Wzy amino acid sequence using TM-PREDICT indicated that Rfc/Wzy had 10-13 transmembrane segments. The computer prediction models were tested by genetically fusing C-terminal deletions of Rfc/Wzy to alkaline phosphatase and beta-galactosidase. Rfc::PhoA fusion proteins near the amino-terminal end were detected by Coomassie blue staining and Western blotting using anti-PhoA serum. The enzyme activities of cells with the rfc/wzy fusions and the location of the fusions in rfc/wzy indicated that Rfc/Wzy has 12 transmembrane segments with two large periplasmic domains, and that the amino- and carboxy-termini are located on the cytoplasmic face of the membrane.

Alkaline Phosphatase↗
PubMed2005

Molecular dynamics simulation of cocaine binding with human butyrylcholinesterase and its mutants.

Molecular dynamics (MD) simulations were carried out to study cocaine binding with wild-type human butyrylcholinesterase (BChE) and its mutants based on a recently reported X-ray crystal structure of human BChE. For each BChE-cocaine system, we simulated both the nonprereactive and prereactive complexes in water. Despite the significant difference found at the acyl binding pocket, the simulated structures confirm the fundamental structural and mechanistic insights obtained from earlier computational studies of wild-type BChE with cocaine based on a homology model, e.g. the rate-determining step for BChE-catalyzed hydrolysis of biologically active (-)-cocaine is the (-)-cocaine rotation in the active site from the nonprereactive BChE-(-)-cocaine complex to the prereactive complex. It has been demonstrated that the MD simulations on both the nonprereactive and prereactive BChE-cocaine complexes can clearly reveal whether specific mutations produce the desired BChE-(-)-cocaine binding structures in which the (-)-cocaine rotation is less hindered while the required prereactive BChE-(-)-cocaine binding is maintained. Based on the MD simulations, both A328W/Y332A and A328W/Y332G BChE's are expected to have catalytic activity for (-)-cocaine hydrolysis higher than that of wild-type BChE and the activity of A328W/Y332G BChE should be slightly higher than that of A328W/Y332A BChE due to the less-hindered (-)-cocaine rotation in the mutant BChE's. However, the less-hindered (-)-cocaine rotation is only a necessary condition for a higher activity mutant BChE. The (-)-cocaine rotation is also less hindered in A328W/Y332A/Y419S BChE, but (-)-cocaine binds with A328W/Y332A/Y419S BChE in a way that is not suitable for the catalysis. Thus, A328W/Y332A/Y419S BChE is expected to lose the catalytic activity. The computational predictions were confirmed by our experimental kinetic data, demonstrating that the MD simulation-based computational protocol used in this study is reliable in prediction of the catalytic activity of BChE mutants for (-)-cocaine hydrolysis.

Butyrylcholinesterase↗
PubMed1999

Human and nematode orthologs--lessons from the analysis of 1800 human genes and the proteome of Caenorhabditis elegans.

Recently, we have defined and analyzed over 1800 orthologous human and rodent genes. Here we extend this work to compare human and Caenorhabditis elegans coding sequences. 1880 human proteins were compared with about 20000 predicted nematode proteins presumably comprising nearly the complete proteome of C. elegans. We found that 44% of human/rodent orthologs have convincing nematode counterparts. On average, the amino acid similarity and identity between aligned human and C. elegans orthologous gene products are 69.3% and 49.1% respectively, and the nucleotide identity is 49.8%. Detailed investigation of our results suggests that some nematode gene predictions are incorrect, leading to erroneous pairing with human genes (e.g. calcineurin and polymerase II elongation factor III). Furthermore, other proteins (i.e. homologs of human ribosomal proteins S20 and L41, thymosin) are missing entirely from the nematode proteome, suggesting that it may not be complete. These results underscore the fact that metazoan gene prediction is a very challenging task and that most computer-predicted nematode genes require supporting evidence of their existence from comparative genomics and/or laboratory investigation.

Animals↗
PubMed2005

Directionality theory: a computational study of an entropic principle in evolutionary processes.

Analytical studies of evolutionary processes based on the demographic parameter entropy-a measure of the uncertainty in the age of the mother of a randomly chosen newborn-show that evolutionary changes in entropy are contingent on environmental constraints and can be characterized in terms of three tenets: (i) a unidirectional increase in entropy for populations subject to bounded growth constraints; (ii) a unidirectional decrease in entropy for large populations subject to unbounded growth constraints; (iii) random, non-directional change in entropy for small populations subject to unbounded growth constraints. This article aims to assess the robustness of these analytical tenets by computer simulation. The results of the computational study are shown to be consistent with the analytical predictions. Computational analysis, together with complementary empirical studies of evolutionary changes in entropy underscore the universality of the entropic principle as a model of the evolutionary process.

Biological Evolution↗
PubMed2004

Comparison of predictive ability of water solubility QSPR models generated by MLR, PLS and ANN methods.

ADME/Tox computational screening is one of the most hot topics of modern drug research. About one half of the potential drug candidates fail because of poor ADME/Tox properties. Since the experimental determination of water solubility is time-consuming also, reliable computational predictions are needed for the pre-selection of acceptable "drug-like" compounds from diverse combinatorial libraries. Recently many successful attempts were made for predicting water solubility of compounds. A comprehensive review of previously developed water solubility calculation methods is presented here, followed by the description of the solubility prediction method designed and used in our laboratory. We have selected carefully 1381 compounds from scientific publications in a unified database and used this dataset in the calculations. The externally validated models were based on calculated descriptors only. The aim of model optimization was to improve repeated evaluations statistics of the predictions and effective descriptor scoring functions were used to facilitate quick generation of multiple linear regression analysis (MLR), partial least squares method (PLS) and artificial neural network (ANN) models with optimal predicting ability. Standard error of prediction of the best model generated with ANN (with 39-7-1 network structure) was 0.72 in logS units while the cross validated squared correlation coefficient (Q(2)) was better than 0.85. These values give a good chance for successful pre-selection of screening compounds from virtual libraries, based on the predicted water solubility.

Chemical Phenomena↗
PubMed1987

Mediastinal infiltration of lung carcinoma (T4N0-1): the positive predictive value of computed tomography.

The value of computed tomography (CT) in predicting direct mediastinal infiltration of stage T4N0-1 lung carcinoma was evaluated prospectively in 11 patients with surgical and histological proof. Furthermore, its role in twelve non-operated patients was assessed retrospectively. The radiologic signs detected independently by two radiologists correlated in 90%. Mediastinal infiltration was verified in 7 of 11 patients (63%). Only in 3 out of the 12 patients treated non-surgically was CT the only criterium for inoperability. In all other patients additional findings, such as scintigraphy, radiologic or bioptic proof of distant metastases, supported inoperability. The limited specificity of CT (63%) demands aggressive staging procedures before any patient is excluded from surgery, the only potentially curative treatment.

Adult↗
PubMed2005

ERTargetDB: an integral information resource of transcription regulation of estrogen receptor target genes.

The estrogen receptor (ER) plays an important role in several physiologic functions of both the reproductive and non-reproductive systems. Malignancies of the ER have been associated with the development of cancers, including those of the prostate and breast. Hence it has become of significant importance to characterize the transcriptional regulation of ER target genes. We have created ERTargetDB in order to integrate the previously published ER target gene information that is available in various publications and databases. This information resource provides researchers with an easy access to ER target genes and the regulatory mechanisms in the corresponding promoters. The current version contains 40 genes with experimentally verified estrogen response elements (EREs), 32 experimentally verified ERE tethering sites, 40 genes identified by the chromatin immunoprecipitation microarray, 381 genes from gene expression microarray and 2948 genes from computational prediction. ERTargetDB provides an integral information resource for direct target genes of ERs for the endocrinology research community. It should prove useful in the investigation of gene regulation and aid the development of computational tools for the prediction of ER target genes.

Animals↗
PubMed1992

Computational complexity of a problem in molecular structure prediction.

The computational task of protein structure prediction is believed to require exponential time, but previous arguments as to its intractability have taken into account only the size of a protein's conformational space. Such arguments do not rule out the possible existence of an algorithm, more selective than exhaustive search, that is efficient and exact. (An efficient algorithm is one that is guaranteed, for all possible inputs, to run in time bounded by a function polynomial in the problem size. An intractable problem is one for which no efficient algorithm exists.) Questions regarding the possible intractability of problems are often best answered using the theory of NP-completeness. In this treatment we show the NP-hardness of two typical mathematical statements of empirical potential energy function minimization of macromolecules. Unless all NP-complete problems can be solved efficiently, these results imply that a function minimization algorithm can be efficient for protein structure prediction only if it exploits protein-specific properties that prohibit the simple geometric constructions that we use in our proofs. Analysis of further mathematical statements of molecular structure prediction could constitute a systematic methodology for identifying sources of complexity in protein folding, and for guiding development of predictive algorithms.

Algorithms↗