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PubMed2003

Unexpected correlations between gene expression and codon usage bias from microarray data for the whole Escherichia coli K-12 genome.

Escherichia coli has long been regarded as a model organism in the study of codon usage bias (CUB). However, most studies in this organism regarding this topic have been computational or, when experimental, restricted to small datasets; particularly poor attention has been given to genes with low CUB. In this work, correspondence analysis on codon usage is used to classify E.coli genes into three groups, and the relationship between them and expression levels from microarray experiments is studied. These groups are: group 1, highly biased genes; group 2, moderately biased genes; and group 3, AT-rich genes with low CUB. It is shown that, surprisingly, there is a negative correlation between codon bias and expression levels for group 3 genes, i.e. genes with extremely low codon adaptation index (CAI) values are highly expressed, while group 2 show the lowest average expression levels and group 1 show the usual expected positive correlation between CAI and expression. This trend is maintained over all functional gene groups, seeming to contradict the E.coli-yeast paradigm on CUB. It is argued that these findings are still compatible with the mutation-selection balance hypothesis of codon usage and that E.coli genes form a dynamic system shaped by these factors.

Bias↗
PubMed1999

No teratogenic effect after clotrimazole therapy during pregnancy.

We evaluated the potential teratogenic effects of vaginal and/or topical administration of clotrimazole in the large population-based dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities (1980-1992). The dataset included 18,515 case pregnancies and 32,804 control pregnancies; 7.1% of case and 7.7% of control women used clotrimazole during pregnancy. Clotrimazole use was not clearly associated with an increase in the total (fetal + birth) prevalence of any congenital abnormality group. There was, however, a suggestion that clotrimazole use was associated with a decrease in the prevalence of undescended testis (prevalence odds ratio = 0.72; 95% confidence interval = 0.54-0.95).

Abnormalities, Drug-Induced↗
PubMed2000

Data quality in predictive toxicology: identification of chemical structures and calculation of chemical properties.

Every technique for toxicity prediction and for the detection of structure-activity relationships relies on the accurate estimation and representation of chemical and toxicologic properties. In this paper we discuss the potential sources of errors associated with the identification of compounds, the representation of their structures, and the calculation of chemical descriptors. It is based on a case study where machine learning techniques were applied to data from noncongeneric compounds and a complex toxicologic end point (carcinogenicity). We propose methods applicable to the routine quality control of large chemical datasets, but our main intention is to raise awareness about this topic and to open a discussion about quality assurance in predictive toxicology. The accuracy and reproducibility of toxicity data will be reported in another paper.

Data Interpretation, Statistical↗
PubMed2025

aPhyloGeo: a Python application for correlating genetic and climatic conditions.

MOTIVATION: Environmental variation and its influence on genetic diversity is a central topic in evolutionary biology and phylogeography. Accurate correlations between genetic and climatic datasets to understand the genetic adaptations of different species to specific environments. It requires integrated and reproducible workflows. RESULTS: We developed aPhyloGeo, an open-source and multiplatform application implemented in Python, for investigating correlations between genetic variation and environmental data within a phylogenetic framework. The workflow integrates multiple analytical steps, including sequence alignment, sliding window phylogenetic inference, and statistical approaches such as the Mantel test and the Procrustean randomization test. These analyses enable the identification of mutation hotspots that exhibit strong associations with environmental variables. In addition, aPhyloGeo supports multicore data processing and provides a fully reproducible pipeline for evaluating localized relationships between genomic variation and climatic distributions. AVAILABILITY AND IMPLEMENTATION: aPhyloGeo is freely available on GitHub at: https://github.com/tahiri-lab/aPhyloGeo, as both a PyPI package and as Python scripts for Linux, macOS, and Windows.

Software↗
PubMed1994

Unlocking datasets.

Explore the source record for details and available documents.

Databases, Factual↗
PubMed1997

Population-based case-control study of teratogenic potential of corticosteroids.

The teratogenic potential of oral and topical corticosteroid treatment during pregnancy was evaluated in the population-based large dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1994. Corticosteroid tablet pregnancy exposure was 1.55% among 20,830 malformed cases and 1.41% among 35,727 healthy control births (P = 0.2). Corticosteroid ointment pregnancy exposure was 0.35% among malformed and 0.33% among control births (P = 0.7). The absolute risk of oral and ointment corticosteroid treatment was low in pregnancy and particularly in the second and third months of gestation, i.e., in the critical period for major congenital abnormalities. The adjusted odds ratio and the analysis of case-control pairs did not show any association between the rate of different congenital abnormalities and the corticosteroid treatment in the second and third months of gestation. Thus, treatments with corticosteroids in pregnancy do not appear to noticeably increase the risk of congenital abnormalities in humans.

Abnormalities, Drug-Induced↗
PubMed2005

Statistical and computational methods for comparative proteomic profiling using liquid chromatography-tandem mass spectrometry.

The combined method of LC-MS/MS is increasingly being used to explore differences in the proteomic composition of complex biological systems. The reliability and utility of such comparative protein expression profiling studies is critically dependent on an accurate and rigorous assessment of quantitative changes in the relative abundance of the myriad of proteins typically present in a biological sample such as blood or tissue. In this review, we provide an overview of key statistical and computational issues relevant to bottom-up shotgun global proteomic analysis, with an emphasis on methods that can be applied to improve the dependability of biological inferences drawn from large proteomic datasets. Focusing on a start-to-finish approach, we address the following topics: 1) low-level data processing steps, such as formation of a data matrix, filtering, and baseline subtraction to minimize noise, 2) mid-level processing steps, such as data normalization, alignment in time, peak detection, peak quantification, peak matching, and error models, to facilitate profile comparisons; and, 3) high-level processing steps such as sample classification and biomarker discovery, and related topics such as significance testing, multiple testing, and choice of feature space. We report on approaches that have recently been developed for these steps, discussing their merits and limitations, and propose areas deserving of further research.

Animals↗
PubMed2004

PSA after radiation for prostate cancer.

The introduction of prostate-specific antigen (PSA) as a reliable tumor marker for prostate cancer brought significant changes in the end points used for outcome reporting after therapy. With regard to a definition of failure after radiation, a consensus was reached in 1996 that took into account the particular issues of an intact prostate after therapy. Over the next several years, the consensus definition issued by the American Society for Therapeutic Radiology and Oncology (ASTRO) was used and studied. Concerns and criticisms were raised. The sensitivity and specificity of this definition vs other proposals has been investigated, and differences in outcome analyzed and compared. Although the ASTRO definition came from analysis of datasets on external-beam radiation and most of the work on this topic has been with this modality, failure definitions for brachytherapy must be explored as well. The concept of a universal definition of failure that might be applied to multiple modalities, including surgery, should also be investigated, at least for comparative study and research purposes.

Brachytherapy↗
PubMed1997

UK National Transplant Database retransplantation in the UK and Republic of Ireland, 1987-1996. UKTSSA National Transplant Database.

At the end of 1996, 1,635 kidney, 17 liver and 24 cardiothoracic recipients were registered on the UK and Republic of Ireland national transplant waiting list to receive a second or subsequent transplant. These patients represented 20%, 9% and 4% of the total separate waiting lists, respectively. This clearly demonstrates a continuing requirement for retransplantation. A study of the characteristics of first and retransplant recipients and their donors shows that retransplant recipients tend to be younger and in the case of liver and heart/lung transplants are less likely to be male. Survival of liver regrafts is significantly worse than first transplant survival. Multifactorial analysis of the factors affecting the outcome of kidney retransplants showed outcome to be associated with the survival time of the first transplant. In the case of kidney transplantation, the younger and the better matched recipients selected for retransplant may at least partially explain the comparable one-year transplant survival estimates for first and retransplants of 81% and 78%, respectively, for the 1986-1993 dataset of 23 centers.

Adolescent↗
PubMed2004

Efficient training of RBF networks for classification.

Radial Basis Function networks with linear outputs are often used in regression problems because they can be substantially faster to train than Multi-layer Perceptrons. For classification problems, the use of linear outputs is less appropriate as the outputs are not guaranteed to represent probabilities. We show how RBFs with logistic and softmax outputs can be trained efficiently using the Fisher scoring algorithm. This approach can be used with any model which consists of a generalised linear output function applied to a model which is linear in its parameters. We compare this approach with standard non-linear optimisation algorithms on a number of datasets.

Algorithms↗
PubMed2002

Doctorial dissertations on nurse practitioners: 1970-2000.

PURPOSE: To understand more about the nurse practitioner (NP) profession, a study was undertaken of the dissertation literature. DATA SOURCES: A search of Dissertation Abstracts Online yielded 134 dissertations that included NPs in the title or abstract and were awarded between 1970 and 2000. CONCLUSIONS: Most of the degrees are either PhD (61%) or EdD (27%). State-based universities produced the most degrees (70%) and six universities accounted for one-fourth of the degrees. The topics of NP-focused dissertations are wide ranging and include history, medical economics and managed care, NP education and professional role, and clinical and behavioral research. IMPLICATIONS FOR PRACTICE: This dataset provides an important source of information for research on the NP profession.

Academic Dissertations as Topic↗
PubMed1993

Correlation of carcinogenic potency with mouse-skin 32P-postlabeling and muta-Rmouse lac Z- mutation data for DMBA and its K-region sulphur isostere: comparison with activities observed in standard genotoxicity assays.

The genotoxicities in vitro and in vivo of the mouse-skin carcinogen 7,12-dimethylbenz[a]anthracene (DMBA) have been compared with those of its weakly carcinogenic 4,5-sulphur analogue, 6,11-dimethylbenzo[b]naphtho-[2,3-d]thiophene (S-DMBA). The only datasets that correlated with the relative carcinogenicity of these agents to the skin were those conducted using topically exposed mouse skin. Thus, both chemicals induced lacZ- mutations in the skin of lacZ+ transgenic mice, and both produced DNA adducts on mouse-skin DNA as assessed using the 32P-postlabeling technique. In each case, DMBA gave a stronger response than did S-DMBA. In contrast to these responses, only DMBA was active in the mouse bone-marrow micronucleus assay and in the C3H10T1/2 in vitro cell transformation assay. Both chemicals were mutagenic to Salmonella and of approximately equal potency. The molecular geometry of DMBA and S-DMBA are compared, and divergent CASE predictions of activity in the Salmonella assay and skin-painting bioassay are discussed. The importance of conducting predictive genotoxicity assays in systems close to those in which carcinogenicity is to be assessed is emphasized by these data.

Aniline Compounds↗
PubMed2003

Noise sensitivity and reactions to noise and other environmental conditions.

This article integrates findings from the literature and new results regarding noise sensitivity. The new results are based on analyses of 28 combined datasets (N = 23,038), and separate analyses of a large aircraft noise study (N = 10,939). Three topics regarding noise sensitivity are discussed, namely, its relationship with noise exposure, its working mechanism, and the scope of its influence. (1) A previous review found that noise sensitivity has no relationship with noise exposure. The current analyses give consistent results, and show that there is at most a very weak positive relationship. (2) It was observed earlier that noise sensitivity alters the effect of noise exposure on noise annoyance, and does not (only) have an additive effect. The current analyses confirm this, and show that the relation of the annoyance score with the noise exposure is relatively flat for nonsensitives while it is steeper for sensitives. (3) Previous studies showed that noise sensitivity also influences reactions other than noise annoyance. The current analyses of the aircraft noise study extend these results, but also indicate that noise sensitivity has relatively little influence on reactions to nonenvironmental conditions.

Aircraft↗
PubMed2004

TopNet: a tool for comparing biological sub-networks, correlating protein properties with topological statistics.

Biological networks are a topic of great current interest, particularly with the publication of a number of large genome-wide interaction datasets. They are globally characterized by a variety of graph-theoretic statistics, such as the degree distribution, clustering coefficient, characteristic path length and diameter. Moreover, real protein networks are quite complex and can often be divided into many sub-networks through systematic selection of different nodes and edges. For instance, proteins can be sub-divided by expression level, length, amino-acid composition, solubility, secondary structure and function. A challenging research question is to compare the topologies of sub- networks, looking for global differences associated with different types of proteins. TopNet is an automated web tool designed to address this question, calculating and comparing topological characteristics for different sub-networks derived from any given protein network. It provides reasonable solutions to the calculation of network statistics for sub-networks embedded within a larger network and gives simplified views of a sub-network of interest, allowing one to navigate through it. After constructing TopNet, we applied it to the interaction networks and protein classes currently available for yeast. We were able to find a number of potential biological correlations. In particular, we found that soluble proteins had more interactions than membrane proteins. Moreover, amongst soluble proteins, those that were highly expressed, had many polar amino acids, and had many alpha helices, tended to have the most interaction partners. Interestingly, TopNet also turned up some systematic biases in the current yeast interaction network: on average, proteins with a known functional classification had many more interaction partners than those without. This phenomenon may reflect the incompleteness of the experimentally determined yeast interaction network.

Algorithms↗
PubMed2000

Skills and topics in continuing medical education for rural doctors.

BACKGROUND: Organizations that fund and produce continuing medical education (CME) activities must have up-to-date information on the needs of their participants. The paper describes a method for assessing priorities for the provision of facilities to rural doctors in Australia for educational topics and skills upgrades. It uses an instrument designed to establish a measure of knowledge and skills that records the difference between the "current felt need" and "desired level of competence." METHODS: A questionnaire was sent to all identifiable rural doctors throughout Australia, including participants in various types of practice. The resulting dataset is designed for future dissection and comparison of subsets by gender, practice size, rurality, and style of practice (whether procedural). It seeks to deliver a prioritized list of educational topics based on subjective gap analysis with weighting on the degree to which the need is unmet. RESULTS: There was considerable consonance between the major "felt needs" and other measures of need. IMPLICATIONS: In spite of statistical deficiencies, which would be corrected in future work, the method offers a new instrument to prioritize the use of resources for CME delivery.

Australia↗