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theBIGbam: compression and interactive exploration of large-scale sequencing alignments with circular mapping support.

SUMMARY: theBIGbam (github.com/bhagavadgitadu22/theBIGbam) is a genome browser and alignment viewer designed for massive metagenomic and metatranscriptomic datasets. The tool takes BAM files containing read alignments, together with genome assemblies in FASTA format or annotated genome sequences in GenBank format. Alternatively, it can start from raw FASTQ reads and generate alignments using a modified mapper that supports circular genomes, enabling seamless read mapping across genome ends. theBIGbam can compress hundreds of gigabytes of input files 10- to 100-fold into dedicated databases while retaining key per-position information, including coverage depth and recurrent mismatches, insertions, and deletions between reads and the reference. These databases can be served to a local web browser, enabling interactive exploration of any contig in any sample using DNAFeaturesViewer for genome maps and Bokeh for mapping-derived features. Contig-sample pairs available for visualization can be filtered using a range of summary metrics calculated per contig, per sample, and per contig-sample pair to guide users toward the most relevant signals. Through its interactive visualization, theBIGbam facilitates the exploration of complex datasets, while its integrated database-combining assembly features, annotated features, and mapping-derived features-provides the information needed to investigate biological hypotheses systematically. Designed to complement existing browsing tools like IGV and Anvi'o, theBIGbam is particularly suited for examining misassemblies, subpopulations, microdiversity, and contig topology in large-scale datasets. AVAILABILITY AND IMPLEMENTATION: theBIGbam is an open-source Rust/Python package that can be installed from Bioconda or PyPI. The source code and documentation are available on GitHub (github.com/bhagavadgitadu22/theBIGbam).

Software↗

Librarian participation in meta-analysis projects.

Meta-analysis is an epidemiological and statistical tool used to combine the results of independent studies and synthesize their conclusions for the purpose of evaluating therapeutic effectiveness, determining procedural efficacy, or providing a basis for development of treatment protocols. Meta-analysis also may be described as "studying the studies." The process, however defined, requires access to a large quantity of medical literature and presents new opportunities for medical librarians to use their data gathering skills. At Dartmouth Hitchcock Medical Center, a librarian assists with the identification, location, and review of literature in support of meta-analysis projects done by the Technology Assessment Program. Comprehensive literature searches are performed and references with abstracts, indexing terms, and other elements of the unit record are downloaded, converted, and presented as records in a database program. References are then analyzed, decisions are made about their relevance, and article copies are acquired for further analysis.

Librarians↗

BOLD--a biological O-linked glycan database.

Glycans can be O-linked to proteins via the hydroxyl group of serine, threonine, tyrosine, hydroxylysine or hydroxyproline. Sometimes the glycan is O-linked to the hydroxyl group via a phosphodiester bond. The core monosaccharide residue may be N-acetylgalactosamine, N-acetylglucosamine, galactose, glucose, fucose, mannose, xylose or arabinose. These O-linked glycans can remain as a monosaccharide, but often a complex structure is built up by stepwise addition of monosaccharides. Monosaccharides known to be added include galactose, N-acetylglucosamine, fucose, N-acetylneuraminic acid, N-glycolylneuraminic acid and 2-keto-3-deoxynonulosonic acid. O-linked glycans can also contain sulfate and phosphate residues. This leads to the possibility of the existence of numerous O-glycan structures. The biological O-linked database (BOLD) is a relational database that contains information on O-linked glycan structures, their biological sources (with a link to the SWISS-PROT protein database), the references in which the glycan was described (with a link to MEDLINE), and the methods used to determine the glycan structure. The database provides a valuable resource for glycobiology researchers interested in O-linked oligosaccharide structures that have been previously described on proteins from different species and tissues.

Carbohydrate Conformation↗

Gene prediction by pattern recognition and homology search.

This paper presents an algorithm for combining pattern recognition-based exon prediction and database homology search in gene model construction. The goal is to use homologous genes or partial genes existing in the database as reference models while constructing (multiple) gene models from exon candidates predicted by pattern recognition methods. A unified framework for gene modeling is used for genes ranging from situations with strong homology to no homology in the database. To maximally use the homology information available, the algorithm applies homology on three levels: (1) exon candidate evaluation, (2) gene-segment construction with a reference model, and (3) (complete) gene modeling. Preliminary testing has been done on the algorithm. Test results show that (a) perfect gene modeling can be expected when the initial exon predictions are reasonably good and a strong homology exists in the database; (b) homology (not necessarily strong) in general helps improve the accuracy of gene modeling; (c) multiple gene modeling becomes feasible when homology exists in the database for the involved genes.

Algorithms↗

Identifying exceptions in a database of recognition failure studies from 1973 to 1992.

This paper presents a database of all published studies based on the recognition failure paradigm, which involves the study of pairs of items followed by a recognition test of the second item of each pair and a recall test of the same target item with the first item of each pair provided as a context cue. The paper also identifies, on the basis of a quantitative analysis, exceptions to the recognition failure function encompassing most data in the database. The database includes reference information about each study and a short description of materials and the manipulations made in each of the 302 experimental conditions reported. The database also includes information about the total number of observations for each condition, the overall hit rate in free or forced choice recognition, the overall probability of recall, the observed probability of recognition given recall, the predicted probability of recognition given recall, the difference between observed and predicted values, and the critical ratio between these difference scores and their overall standard deviation.

Computers↗

Unique NS5b hepatitis C virus gene sequence consensus database is essential for standardization of genotype determinations in multicenter epidemiological studies.

A multicenter study of NS5b hepatitis C virus (HCV) genotype determination involving 12 laboratories demonstrates that any laboratory with expertise in sequencing techniques would be able to provide a reliable HCV genotype for clinical and epidemiological purposes as long as they are provided a consensus reference sequence database.

Consensus Sequence↗

Tentative reference values for nickel concentrations in human serum, plasma, blood, and urine: evaluation according to the TRACY protocol.

Published reports of Ni concentrations in human serum or plasma, whole blood, and urine have been reviewed in order to establish a database of reference values. In keeping with the TRACY program as previously applied to Hg, reports were evaluated in the categories of description of sample population, specimen collection and processing, analytical methods, and data presentation. Based on these considerations, eight studies of Ni in serum were deemed suitable for establishing reference levels in the general population. In five of these studies, the mean values for serum Ni concentration were < 0.3 microgram/l and the upper limits were < or = 1.1 micrograms/l. Six studies of Ni in urine were found suitable, and in four of these the mean values of Ni were < or = 2.0 micrograms/l and the upper limits were < or = 6.0 micrograms/l. Fewer studies on Ni in whole blood have been reported, and the Ni content of blood remains uncertain.

Humans↗

Transterm: a database of mRNAs and translational control elements.

Transterm is a database that facilitates studies of translation and the translational control of protein synthesis. It contains a curated collection of elements in mRNAs that control translation, and biologically relevant mRNA regions extracted from GenBank. It is organised largely on a taxonomic basis with files and summaries for each species. Global patterns that may affect translation in particular species, for example bias in the context of initiation codons (Kozak's consensus or Shine-Dalgarno sequences) or termination codons, can be detected in the consensus and information content bias summaries. Several types of access are provided via a web browser interface. Transterm defined elements may be matched in a user's sequence or in the database. Alternatively, elements can be entered by the user to search specific sections of the database (for example, coding regions or 3' flanking regions or the 3'-UTRs) or the user's sequence. Each Transterm defined element has an associated biological description with references. The database is accessible at http://uther.otago.ac.nz/Transterm.html.

Animals↗

Bibliography database managers. A comparative review.

Bibliography database managers (BDMs) are used to manage information resources: specifically, to maintain a database of references and create bibliographies and reference lists for written works. This comparative review provides an overview of BDMs and capsule reviews of five programs: EndNote Plus 2.0; Library Master 3.0; Papyrus 7.0.11; Pro-Cite 2.2.1; and Reference Manager 6.02.

Bibliographies as Topic↗

Molecular genetic identification of southern hemisphere beaked whales (Cetacea: Ziphiidae).

To assist in the species-level identification of stranded and hunted beaked whales, we compiled a database of 'reference' sequences from the mitochondrial DNA control region for 15 of the 20 described ziphiid species. Reference samples for eight species were obtained from stranded animals in New Zealand and South Australia. Sequences for a further seven species were obtained from a previously published report. This database was used to identify 20 'test' samples obtained from incompletely documented strandings around New Zealand. Analyses showed that four of these 'test' specimens (20%) had initially been misidentified. These included two animals of particular interest: (i) a Blainville's beaked whale (Mesoplodon densirostris), the first record of this species in New Zealand waters; and, (ii) a juvenile Andrews' beaked whale (Mesoplodon bowdoini), a species known from just over 20 strandings worldwide. A published sequence from a beaked whale product purchased in the Republic of Korea was identified as a Cuvier's beaked whale (Ziphius cavirostris). Levels of intra- and interspecific variation were compared to determine the potential for misidentification when the database or taxonomy is incomplete. Intraspecific variation was generally < 2%, and interspecific divergence was generally > 4.7%. Exceptions were within-species variation in Hyperoodon planifrons, southern bottlenosed whale (4.12%), which exceeded the variation between the two species of Berardius (3.78%), and variation between the two specimens assigned to M. hectori, Hector's beaked whale (7.14%). The latter case appears to be an error in species identification, and could represent the discovery of a new species of beaked whale.

Animals↗

OptStrain: a computational framework for redesign of microbial production systems.

This paper introduces the hierarchical computational framework OptStrain aimed at guiding pathway modifications, through reaction additions and deletions, of microbial networks for the overproduction of targeted compounds. These compounds may range from electrons or hydrogen in biofuel cell and environmental applications to complex drug precursor molecules. A comprehensive database of biotransformations, referred to as the Universal database (with >5700 reactions), is compiled and regularly updated by downloading and curating reactions from multiple biopathway database sources. Combinatorial optimization is then used to elucidate the set(s) of non-native functionalities, extracted from this Universal database, to add to the examined production host for enabling the desired product formation. Subsequently, competing functionalities that divert flux away from the targeted product are identified and removed to ensure higher product yields coupled with growth. This work represents an advancement over earlier efforts by establishing an integrated computational framework capable of constructing stoichiometrically balanced pathways, imposing maximum product yield requirements, pinpointing the optimal substrate(s), and evaluating different microbial hosts. The range and utility of OptStrain are demonstrated by addressing two very different product molecules. The hydrogen case study pinpoints reaction elimination strategies for improving hydrogen yields using two different substrates for three separate production hosts. In contrast, the vanillin study primarily showcases which non-native pathways need to be added into Escherichia coli. In summary, OptStrain provides a useful tool to aid microbial strain design and, more importantly, it establishes an integrated framework to accommodate future modeling developments.

Algorithms↗

The development of variable MLM editor and TSQL translator based on Arden Syntax in Taiwan.

The Arden Syntax standard has been utilized in the medical informatics community in several countries during the past decade. It is never used in nursing in Taiwan. We try to develop a system that acquire medical expert knowledge in Chinese and translates data and logic slot into TSQL Language. The system implements TSQL translator interpreting database queries referred to in the knowledge modules. The decision-support systems in medicine are data driven system where TSQL triggers as inference engine can be used to facilitate linking to a database.

Artificial Intelligence↗

Unknown identification using reference mass spectra. Quality evaluation of databases.

The high success of the "uncertified" mass spectrometry spectral collection started in 1956 demonstrated qualitatively that a partial reference mass spectrum, even one measured routinely, can be of real value. Correct matchings were still possible despite reference errors, which almost never led to close matches that were incorrect. This study shows quantitatively that the number of different compounds, not the number of peaks in a spectrum, is by far the most important determinant of database efficiency for identifying a "global" unknown. A statistical evaluation of matching performance shows that only 6, 12, and 18 peaks in a reference spectrum are 13%, 67%, and 96%, respectively, as valuable as hundreds of peaks. Also, a separately measured second spectrum of the same compound is 50% as valuable as the first. Database expansion that tripled the number of possible wrong answers only reduced the proportion of correct identifications by 5%. Corrections of a mass or abundance error in each of six reference spectra increase the database matching performance by as much as the addition of one spectrum of a new compound. A new "matching quality index" based statistically on these values indicates that the largest database is also by far the most effective for matching unknowns.

Animals↗

Body height changes with hyperextension.

OBJECTIVE: To automatize the lumbar physical examination with an acceptable rate of error. DESIGN: An external skin marker method for automatizing the physical examination was developed and its ability to discriminate between normal and abnormal subjects tested in a blind clinical trial. BACKGROUND: The low reproducibility of clinical findings, even among experienced doctors, has been well documented. This is of particular concern and may explain why there is such a wide variation in surgical rates across the USA (tenfold for disc herniation). Inconsistencies among physicians in the evaluation of benign low back conditions make standardization desirable. METHODS: A computerized physical examination was used to evaluate patients with low back pain and compare their results with a normative database obtained from a selection of healthy subjects. A high-resolution motion analysis system tracked the movement of skin markers placed on the midline and pelvis. Surface EMG electrodes placed above L(5) collected data from multifidus. From the kinematics of skin markers during flexion--extension with lifts up to 32 kg, and lateral bending with lifts up to 10 kg, the following parameters were estimated: lumbosacral angle and elongation, contribution of each lumbar segment to the lordosis reduction, relative pelvic/spine motion, and trunk velocity. First the average normal value for each estimated parameter was determined using 40 normal subjects. For each subject the difference between his parameter and the normal was processed by an expert system generating a normality index varying from zero (perfect abnormal) to one (perfect normal). To develop the expert system's rules, a preliminary group of 20 very abnormal subjects was used, such that the normality index separated them from the normals. For validation, a set of 29 back-sprain patients and another set of 42 discogram-positive patients were selected. Each subject was tested and his computerized normality index calculated without any clinician's input, then compared with the clinician's evaluation, which was taken to be the gold standard. The receiver operating characteristic technique was used to quantify the discrepancies. RESULTS: The expert system could detect clinically abnormal subjects with accuracy (sensitivity 83-91% and specificity > 90%) whele providing quantitative information on workers' functional capacities. CONCLUSIONS: Once a reference normative database is agreed upon, each patient can be compared with that reference according to the same rules, with the resulting machine classification being independent of the clinician. This eliminates the inter- and intra-clinician variability in patient follow-up. Because of the severity of the selection criteria, this study is based upon a relatively restricted number of subjects, as well as a limited normative database of 40 subjects. RELEVANCE: It is possible to automate the lumbar physical examination with an acceptable error rate. This technique permits the objective consistent assessment of lumbar function, and thus allows the comparison of different treatment regimes for lumbar dysfunction.

Journal Article↗

SCOP: a structural classification of proteins database.

The Structural Classification of Proteins (SCOP) database provides a detailed and comprehensive description of the relationships of all known proteins structures. The classification is on hierarchical levels: the first two levels, family and superfamily, describe near and far evolutionary relationships; the third, fold, describes geometrical relationships. The distinction between evolutionary relationships and those that arise from the physics and chemistry of proteins is a feature that is unique to this database, so far. SCOP also provides for each structure links to atomic co-ordinates, images of the structures, interactive viewers, sequence data, data on any conformational changes related to function and literature references. The database is freely accessible on the World Wide Web (WWW) with an entry point at URL http://scop.mrc-lmb.cam.ac.uk/scop/

Amino Acid Sequence↗

Intravenous immunoglobulin for suspected or subsequently proven infection in neonates.

BACKGROUND: Congenital and nosocomial infections are important causes of neonatal morbidity and mortality. Maternal transport of immunoglobulins to the fetus mainly occurs after 32 weeks gestation and endogenous synthesis does not begin until several months after birth. Administration of intravenous immunoglobulin provides IgG that can bind to cell surface receptors, provide opsonic activity, activate complement, promote antibody dependent cytotoxicity, and improve neutrophilic chemoluminescence. Theoretically infectious morbidity and morbidity could be reduced by the administration of intravenous immunoglobulin. OBJECTIVES: To assess the effectiveness of intravenous immunoglobulin (IVIG) to reduce mortality/morbidity caused by suspected infection in newborn infants. In secondary analyses to assess the effectiveness of IVIG to reduce mortality/morbidity in those neonates who entered into the studies with suspected infection and who later were confirmed as being infected. SEARCH STRATEGY: Medline, Embase, and Reference Update Databases were searched in November 1997, and the Cochrane Library in July 1998 using the following keywords: immunoglobulin and infant-newborn, and random allocation, or controlled trial, or randomized controlled trial (RCT). The reference lists of identified RCTs and meta-analyses, personal files and Science Citation Index were also searched. No language restrictions were applied. Unpublished data were requested from authors and information has been obtained from one author to date. SELECTION CRITERIA: The criteria used to select studies for inclusion were: 1) DESIGN: RCT (including quasi-randomized trials) 2) Newborn infants (< 28 days old) 3) INTERVENTION: IVIG for treatment of suspected (and in some infants subsequently proved) bacterial/fungal infection compared to placebo or no intervention. Suspected infection was defined as clinical symptoms and signs consistent with infection without isolation of causative organism. Proved infection was defined as: clinical symptoms and signs consistent with infection in association with isolation of causative organism from either blood culture, cerebrospinal fluid culture, urine culture (urine obtained by suprapubic tap) or a normally sterile site (e.g., liver, spleen, meninges, lung) at autopsy. 4) At least one of the following outcomes was reported: mortality during initial hospital stay; length of hospital stay; side effects; psychomotor development/growth at follow up. DATA COLLECTION AND ANALYSIS: Two reviewers independently abstracted information for the outcomes of interest and one researcher (AO) checked for any discrepancies and pooled the results. Relative risk (RR) and Risk Difference (RD) with 95% confidence intervals (CI) using the fixed effects model are reported for dichotomous outcomes and weighted mean difference (WMD) for continuous data. NNT was calculated for outcomes that showed a statistically significant reduction in RD. Data from quasi-randomized trials were excluded in sensitivity analyses. MAIN RESULTS: Study quality was generally poor. Four of 7 identified studies (n = 208), reported on the outcomes of all randomized patients with clinically suspected infection. Mortality was reduced [RR 0.52 (95% CI; 0.28, 0.98), RD -0.102 (95% CI; -0.005, -0.199, NNT 10 (95% CI; 5, 200]. When, in a sensitivity analysis (n = 126), the results from a quasi-randomized trial (n = 82) were excluded, RR and RD remained similar, [RR 0.53 (95% CI; 0.25, 1.15), RD -0.106 (-0.232, 0.021)] but statistical significance was lost. Treatment with IVIG (six trials, n = 234) in cases of subsequently proved infection did not result in a statistically significant reduction in mortality [RR 0.62 (95% CI; 0.34, 1.12, RD -0.074 (95% CI; -0.163, 0. 014)]. Excluding in a sensitivity analysis (n = 199) a quasi-randomized trial (n = 35) changed the results slightly [RR 0. 68 (95% CI; 0.36, 1.29), RD -0.059 (-0.152, 0.035)]. There was no statistically significant between-study

Humans↗

SV40 large tumor antigen (T antigen): database of mutants.

The SV40 T antigen database (http://www.pitt.edu/pipaslab/) lists viruses and plasmids expressing mutant forms of large T antigen. Each entry contains information regarding the mutant designation, mutant type, virus strain, nucleotide change, amino acid change and pertinent references. The database is now available as an internet searchable index.

Antigens, Polyomavirus Transforming↗

Birth rate among patients with epilepsy: a nationwide population-based cohort study in Finland.

Few reports on population-based studies of birth rate among epilepsy patients have been published. In most previous studies, fertility has been lower among epilepsy patients than in the rest of the population. However, conflicting results have also been reported. Because of small samples and selective material, the generalizability of these results is also limited. The authors conducted a population-based cohort study of birth rate (1985-2001) in a nationwide Finnish cohort of patients with newly diagnosed epilepsy and a population-based reference cohort. All patients (n = 14,077) approved as eligible for reimbursement for antiepileptic medication from the Social Insurance Institution of Finland (KELA) for the first time between 1985 and 1994 were identified from the KELA database. A reference cohort (n = 29,828) was identified from the Finnish Population Register Center, with frequency-matching on age. Information on follow-up status and livebirths were also obtained from the Finnish Population Register Center. The birth rate was lower in patients with epilepsy than in the reference cohort among both men (hazard ratio = 0.58, 95% confidence interval: 0.54, 0.62) and women (hazard ratio = 0.88, 95% confidence interval: 0.83, 0.93). There were a clear decreasing trend by age at observation in men with epilepsy and a moderate decreasing trend by age at start of follow-up in women with epilepsy.

Adolescent↗