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[Clinical analysis of 35 patients with retinoblastoma followed-up for 25 years].

The author presents a comprehensive analysis of a group of 35 patients with retinoblastoma followed up for 20 years at the Ophthalmological Clinic of the Faculty Hospital in Bratislava, focused on the aetiology, diagnosis, treatment and prognosis of the disease. Special emphasis is laid on the investigation of indicators which differentiate hereditary and non-hereditary retinoblastoma and on the application of these indicators for the evaluation of the clinical picture and for genetic consultations.

Adult↗

Comparative proteome analysis of culture supernatant proteins from virulent Mycobacterium tuberculosis H37Rv and attenuated M. bovis BCG Copenhagen.

A comprehensive analysis of culture supernatant (CSN) proteins of Mycobacterium tuberculosis H37Rv was accomplished by combination of two-dimensional electrophoresis (2-DE), mass spectrometry, and N-terminal sequencing by Edman degradation. Analytical 2-DE gels resolved approximately 1250 protein spots from CSN of M. tuberculosis H37Rv, 381 of which were identified by mass spectrometry and/or Edman degradation. This study revealed 137 different proteins, 42 of which had previously been described as secreted. Comparative proteome analysis of CSN from virulent M. tuberculosis H37Rv and attenuated Mycobacterium bovis BCG Copenhagen identified 39 M. tuberculosis-specific spots containing 27 different proteins, representing candidate antigens for novel vaccines and diagnostics in tuberculosis. These included five proteins encoded by open reading frames absent from M. bovis BCG, e.g., early secretory antigen target (Esat6), as well as 22 novel differential proteins, such as acetyl-CoA C-acetyltransferase (Rv0243) and two putative Esat6-like proteins (Rv1198, Rv1793).

Bacterial Proteins↗

Mammalian mitochondrial D-loop region structural analysis: identification of new conserved sequences and their functional and evolutionary implications.

This paper reports the first comprehensive analysis of Displacement loop (D-loop) region sequences from ten different mammalian orders. It represents a systematic evolutionary study at the molecular level on regulatory homologous regions in organisms belonging to a well defined class, mammalia, which radiated about 150 million years ago (Mya). We have aligned and analyzed 26 complete D-loop region sequences available in the literature and the fat dormouse sequence, recently determined in our laboratory. The novelty of our alignment consists of the extensive manual revision of the preliminary output obtained by computer program to optimize sequence similarity, particularly for the two peripheral domains displaying heterogeneity in length and the presence of repeated sequences. The multialignment is available at the WWW site: http://www.ba.cnr.it/dloop.html. Our comparative study has allowed us to identify new conserved sequence blocks present in all the species under consideration and events of insertion/deletion which have important implications in both functional and evolutionary aspects. In particular we have detected two blocks, about 60 bp long, extended termination associated sequences (ETAS1 and ETAS2) conserved in all the organisms considered. Evaluation against experimental work suggests a possible functional role of ETAS1 and ETAS2 in the regulation of replication and transcription and targeted experimental approaches. The analyses on conserved sequence blocks (CSBs) clearly indicate that CSB1 is the only very essential element, common to all mammalian mt genomes, while CSB2 and CSB3 could be involved in different though related functions, probably species specific, and thus more linked to nuclear mitochondrial coevolutionary processes. Our hypothesis on the different functional implications of the conserved elements, CSBs and TASs, reported so far as main regulatory signals, would explain the different conservation of these elements in evolution. Moreover the intra-order comparison of the D-loop regions highlights peculiar features useful to define the evolutionary dynamics of this region in closely related species.

Animals↗

USAGE: a web-based approach towards the analysis of SAGE data. Serial Analysis of Gene Expression.

MOTIVATION: SAGE enables the determination of genome-wide mRNA expression profiles. A comprehensive analysis of SAGE data requires software, which integrates (statistical) data analysis methods with a database system. Furthermore, to facilitate data sharing between users, the application should reside on a central server and be accessed via the internet. Since such an application was not available we developed the USAGE package. RESULTS: USAGE is a web-based application that comprises an integrated set of tools, which offers many functions for analysing and comparing SAGE data. Additionally, USAGE includes a statistical method for the planning of new SAGE experiments. USAGE is available in a multi-user environment giving users the option of sharing data. USAGE is interfaced to a relational database to store data and analysis results. The USAGE query editor allows the composition of queries for searching this database. Several database functions have been included which enable the selection and combination of data. USAGE provides the biologist increased functionality and flexibility for analysing SAGE data. AVAILABILITY: USAGE is freely accessible for academic institutions at http://www.cmbi.kun.nl/usage/. The source code of USAGE is freely available for academic institutions on request from the first author.

Databases, Factual↗

The power of an integrated informatic and molecular approach to type 1 diabetes research.

Recent years have witnessed an explosive growth in available biological data. This includes a tremendous quantity of sequence data (e.g., biological structures, genetic and physical maps, pathways) generated by genome and transcriptome projects focused on humans, mice, and a multitude of other species. Diabetes research stands to greatly benefit from this data, which is distributed across public and private databases and the scientific literature. The increasing quantity and complexity of this biological data necessitates use of novel bioinformatics strategies for its efficient retrieval, analysis, and interpretation. Bioinformatic capability is becoming increasingly indispensable for fast and comprehensive analysis of biological data by diabetes researchers. There is great potential for diabetes scientists and clinicians to take advantage of recent bioinformatics and knowledge discovery developments to radically transform and advance this field of research. This paper will review advances in the field of bioinformatics relevant to diabetes research and preview a new specialty diabetes database, Diabetaeta, that we are creating to serve as a central bioinformatic portal for type 1 diabetes research, as well as serving as a public repository for beta cell gene and protein expression data.

Animals↗

[Analysis of the clinical manifestations and imaging features of Budd-Chiari syndrome: report of 81 cases].

A comprehensive analysis of the clinical manifestations and imaging features in 81 cases of Budd-Chiari syndrome (BCS) was conducted, and criteria for classification of this disease was proposed. Diagnostic modalities included digital subtraction angiography, ultrasound, computed tomography and percutaneous transhepatic cholangiography. The main clinical manifestations of BCS was inferior vena cave obstruction and portal hypertension. Wall thickening of the gallbladder was indicative of BCS during imaging diagnosis.

Adolescent↗

Liquid chromatography-mass spectrometry for comprehensive profiling of ceramide molecules in human hair.

Ceramides (CERs) play key roles in signal transduction and cell regulation, probably during the keratinization of human hair. Current methods using mass spectrometry (MS), however, are not sufficient to allow the comprehensive analysis of CER molecules, including isobaric and isomeric CERs. Therefore, a method for the comprehensive profiling of CERs was developed. The method developed is based on reversed-phase liquid chromatography (RPLC) coupled to atmospheric pressure chemical ionization (APCI)-MS. Comprehensive identification and profiling of CERs is achieved using two sets of multimass chromatograms obtained from two channel detections that monitor both molecular-related and sphingoid-related ions under two different in-source collision-induced dissociation conditions and using retention times obtained from RPLC. The application of this method revealed that human hair contains 73 species of CER molecules, which were all corroborated by structural analysis using tandem mass spectrometry. The results further revealed that the composition is characterized by predominant molecules consisting of even carbon atom-containing saturated/unsaturated nonhydroxy or alpha-hydroxy fatty acids and C(18) dihydrosphingosine, a minor but distinct content of isobaric/isomeric and odd chain-containing CERs. This successfully developed RPLC-APCI-MS technique allows the comprehensive profiling of CER molecules in hair for the investigation of their physicochemical and physiological roles.

Adolescent↗

Promoter prediction analysis on the whole human genome.

Promoter prediction programs (PPPs) are important for in silico gene discovery without support from expressed sequence tag (EST)/cDNA/mRNA sequences, in the analysis of gene regulation and in genome annotation. Contrary to previous expectations, a comprehensive analysis of PPPs reveals that no program simultaneously achieves sensitivity and a positive predictive value >65%. PPP performances deduced from a limited number of chromosomes or smaller data sets do not hold when evaluated at the level of the whole genome, with serious inaccuracy of predictions for non-CpG-island-related promoters. Some PPPs even perform worse than, or close to, pure random guessing.

Algorithms↗

Combined analysis from eleven linkage studies of bipolar disorder provides strong evidence of susceptibility loci on chromosomes 6q and 8q.

Several independent studies and meta-analyses aimed at identifying genomic regions linked to bipolar disorder (BP) have failed to find clear and consistent evidence of linkage regions. Our hypothesis is that combining the original genotype data provides benefits of increased power and control over sources of heterogeneity that outweigh the difficulty and potential pitfalls of the implementation. We conducted a combined analysis using the original genotype data from 11 BP genomewide linkage scans comprising 5,179 individuals from 1,067 families. Heterogeneity among studies was minimized in our analyses by using uniform methods of analysis and a common, standardized marker map and was assessed using novel methods developed for meta-analysis of genome scans. To date, this collaboration is the largest and most comprehensive analysis of linkage samples involving a psychiatric disorder. We demonstrate that combining original genome-scan data is a powerful approach for the elucidation of linkage regions underlying complex disease. Our results establish genomewide significant linkage to BP on chromosomes 6q and 8q, which provides solid information to guide future gene-finding efforts that rely on fine-mapping and association approaches.

Bipolar Disorder↗

Long-range periodic patterns in microbial genomes indicate significant multi-scale chromosomal organization.

Genome organization can be studied through analysis of chromosome position-dependent patterns in sequence-derived parameters. A comprehensive analysis of such patterns in prokaryotic sequences and genome-scale functional data has yet to be performed. We detected spatial patterns in sequence-derived parameters for 163 chromosomes occurring in 135 bacterial and 16 archaeal organisms using wavelet analysis. Pattern strength was found to correlate with organism-specific features such as genome size, overall GC content, and the occurrence of known motility and chromosomal binding proteins. Given additional functional data for Escherichia coli, we found significant correlations among chromosome position dependent patterns in numerous properties, some of which are consistent with previously experimentally identified chromosome macrodomains. These results demonstrate that the large-scale organization of most sequenced genomes is significantly nonrandom, and, moreover, that this organization is likely linked to genome size, nucleotide composition, and information transfer processes. Constraints on genome evolution and design are thus not solely dependent upon information content, but also upon an intricate multi-parameter, multi-length-scale organization of the chromosome.

Bacterial Proteins↗

[In silico data mining of the human programmed cell death 5 (PDCD5) sequences].

OBJECTIVE: To lay foundation for the functional studies of programmed cell death 5 (PDCD5) and develop new technical pathway for bioinformatics analysis of human functional genes. METHODS: Using PDCD5 as the target molecule, intensive bioinformatics analysis of the nucleic acid and protein sequences were conducted. Data mining and comprehensive analysis by sequence against database similarity searching, ortholog structure comparison, expression profile analysis and gene "neighbor" listing were performed. RESULTS: Two human putative pseudogenes on chromosomes 12 and 5, and one mouse putative pseudogene on chromosome 1 were identified. The methanobacterium thermoautotrophicum ortholog was classified as the same fold as ubiquitin and ribosomal protein S13. The C. elegans ortholog, ubiquitin and IAP (inhibitor of apoptosis proteins) belonged to the same expression profile cluster. This cluster was related to biosynthesis and protein synthesis. PDCD5 orthologs in various genomes were adjacent to various ribosomal proteins on the chromosome. CONCLUSION: The human genome contains at least two processed pseudogenes of PDCD5. Besides the relationship with cell apoptosis, PDCD5 is predicted to have functional relationship with ubiquitin and participate in the translation regulation.

Amino Acid Sequence↗

[Organization of the Karshi virus strain Leiv-2247 Uz genome and its phylogenetic relationships with other representatives of the Flavivirus genus].

For the first time, the Karshi virus complete genome sequence has been determined and analyzed in this work. The Karshi virus was attributed to the Tick-borne encephalitis group on the basis of phylogenetic analysis of polyprotein sequencing, as well as partial NS5 of the Flavivirus genus. Comprehensive analysis of the longed to its own cluster, which includes also the Royal Farm virus.

Animals↗

Nutrition and national development planning.

We have argued that development strategies aimed at the reduction of all forms of deprivation, according to an explict statement of values and priorities, are necessary for the integration of nutrition planning into overall national development planning. We do not regard this as likely to lead to the neglect of the key issues of investment and production. Instead, we argue that consideration of investment and production strategies should be explicitly directed to their purpose, the reduction of deprivation, rather than, as in the past, treated as the necessary means to that purpose. Thus investment and production strategies would be aimed directly at relieving deprivation including, especially, nutritional deprivation, and their impact in this respect will need to be explicitly predicted and evaluated. We have argued that problems and potentials differ greatly at the area level and that planning must be an iterative process in which national and area-level strategies and programmes are brought to consistency through successive cycles of adjustment and reappraisal. A major role in planning, especially in detailed design and implementation, is assigned to area level. Planning must proceed from an identification of the deprivations under attack to the identification of intervention measures. Elsewhere we have argued the case for the 'functional classification" of malnutrition and the use of "typical profiles" in the understanding of "the ecology and etiology of malnutition". Where planning accepts the need for an integrated approach to the attack on all forms of deprivation, these analyses of nutritional deprivation would from part of a more comprehensive analysis of general deprivation. The existence of "functional classification" and "typical profiles" analysis with respect to malnutrition would provide an excellent base from which a more comprehensive view might be developed. The factors affecting the evolution of nutritional - and other - deprivation problems need to be understood in order that we can identify points in the system where intervention may control theri emergence. In any situation there will be alternative intervention points bearing either directly on the alleviation of symptoms (malnutrition) or, more or less indirectly, on the control of its causes. In general, mixed strategies will be called for. At this stage in our understanding no generalizations are possible about the nature of strategy choices. Our choice of intervention measures must be based upon an understanding of the overall system as it generates malnutrition, and of which forces exert the most powerful effects. One important element of this analysis will be an understanding of the behaviour of the malnourished. However, conventional planning approaches, in which ministries and departments concern themselves only with problems and measures which conform to the definition of their own spheres of responsibility, have failed to define these choices effectively...

Child↗

Comprehensive gas chromatographic analysis of heroin street samples.

A comprehensive analytical approach for heroin street samples is faced with problems associated with differences in polarity, stability and physico-chemical properties of the various substances present. Difficulties with carbohydrates are of particular concern. In this method, which is suitable for screening purposes, 10 mg of sample is dissolved in acetonitrile-trifluoroacetic acid in the presence of methyl orange. Derivatization is then accomplished by O-silylation (MSTFA) and N-trifluoroacetylation (MBTFA). Compounds were detected by flame ionization after a capillary gas chromatographic separation and produced well shaped peaks for the majority of substances. Sugars gave multiple but reproducible chromatographic peaks. By direct derivatization of another aliquot of the solid sample a single predominant chromatographic peak can be obtained for sugars using MSTFA with MBTFA. Alternatively the more potent reagent MSHFB gives highly reproducible results.

Journal Article↗

Medication safety--reliability of preference cards.

A CLINICAL ANALYSIS of surgeons' preference cards was initiated in one hospital as part of a comprehensive analysis to reduce medication-error risks by standardizing and simplifying the intraoperative medication-use process specific to the sterile field. THE PREFERENCE CARD ANALYSIS involved two subanalyses: a review of the information as it appeared on the cards and a failure mode and effects analysis of the process involved in using and maintaining the cards. THE ANALYSIS FOUND that the preference card system in use at this hospital is outdated. Variations and inconsistencies within the preference card system indicate that the use of preference cards as guides for medication selection for surgical procedures presents an opportunity for medication errors to occur.

Drug Information Services↗

New challenges in gene expression data analysis and the extended GEPAS.

Since the first papers published in the late nineties, including, for the first time, a comprehensive analysis of microarray data, the number of questions that have been addressed through this technique have both increased and diversified. Initially, interest focussed on genes coexpressing across sets of experimental conditions, implying, essentially, the use of clustering techniques. Recently, however, interest has focussed more on finding genes differentially expressed among distinct classes of experiments, or correlated to diverse clinical outcomes, as well as in building predictors. In addition to this, the availability of accurate genomic data and the recent implementation of CGH arrays has made mapping expression and genomic data on the chromosomes possible. There is also a clear demand for methods that allow the automatic transfer of biological information to the results of microarray experiments. Different initiatives, such as the Gene Ontology (GO) consortium, pathways databases, protein functional motifs, etc., provide curated annotations for genes. Whereas many resources on the web focus mainly on clustering methods, GEPAS has evolved to cope with the aforementioned new challenges that have recently arisen in the field of microarray data analysis. The web-based pipeline for microarray gene expression data, GEPAS, is available at http://gepas.bioinfo.cnio.es.

Gene Expression Profiling↗

Biologically based analysis of the data for the Colorado uranium miners cohort: age, dose and dose-rate effects.

This study is a comprehensive analysis of the latest follow-up of the Colorado uranium miners cohort using the two-stage clonal expansion model with particular emphasis on effects related to age and exposure. The model provides a framework in which the hazard function for lung cancer mortality incorporates detailed information on exposure to radon and radon progeny from hard rock and uranium mining together with information on cigarette smoking. Even though the effect of smoking on lung cancer risk is explicitly modeled, a significant birth cohort effect is found which shows a linear increase in the baseline lung cancer risk with birth year of the miners in the cohort. The analysis based on the two-stage clonal expansion model suggests that exposure to radon affects both the rate of initiation of intermediate cells in the pathway to cancer and the rate of proliferation of intermediate cells. However, in contrast to the promotional effect of radon, which is highly significant, the effect of radon on the rate of initiation is found to be not significant. The model is also used to study the inverse dose-rate effect. This effect is evident for radon exposures typical for mines but is predicted to be attenuated, and for longer exposures even reversed, for the more protracted and lower radon exposures in homes. The model also predicts the drop in risk with time after exposure ceases. For residential exposures, lung cancer risks are compared with the estimates from the BEIR VI report. While the risk estimates are in agreement with those derived from residential studies, they are about two- to fourfold lower than those reported in the BEIR VI report.

Age Factors↗