Biomedical subjects

S C Bagley

Publications and source records attributed to S C Bagley.

4 recordsLinked to original sources

PubMed2001

Logistic regression in the medical literature: standards for use and reporting, with particular attention to one medical domain.

Logistic regression (LR) is a widely used multivariable method for modeling dichotomous outcomes. This article examines use and reporting of LR in the medical literature by comprehensively assessing its use in a selected area of medical study. Medline, followed by bibliography searches, identified 15 peer-reviewed English-language articles with original data, employing LR, published between 1985 and 1999, pertaining to patient interest in genetic testing for cancer susceptibility. Articles were examined for each of 10 criteria for proper use and reporting of LR models. Substantial shortcomings were found in both use of LR and reporting of results. For many studies, the ratio of the number of outcome events to predictor variables (events per variable) was sufficiently small to call into question the accuracy of the regression model. Additionally, no studies reported validation analysis, regression diagnostics, or goodness-of-fit measures. It is recommended that authors, reviewers, and editors pay greater attention to guidelines concerning the use and reporting of LR models.

Epidemiologic Studies↗

PubMed1996

Conserved features in the active site of nonhomologous serine proteases.

BACKGROUND: Serine protease activity is critical for many biological processes and has arisen independently in a few different protein families. It is not clear, though, the degree to which these protease families share common biochemical and biophysical properties. We have used a computer program to study the properties that are shared by four serine protease active sites with no overall structural or sequence homology. The program systematically compares the region around the catalytic histidines from the four proteins with a set of noncatalytic histidines, used as controls. It reports the three-dimensional locations and level of statistical significance for those properties that distinguish the catalytic histidines from the noncatalytic ones. The method of analysis is general and can be applied easily to other active sites of interest. RESULTS: As expected, some of the reported properties correspond to previously known features of the serine protease active site, including the catalytic triad and the oxyanion hole. Novel properties are also found, including the spatial distribution of charged, polar, and hydrophobic groups arranged to stabilize the catalytic residues, and a relative abundance of some residues (Val, Tyr, Leu, and Gly) around the active site. CONCLUSIONS: Our findings show that in addition to some properties common to all the proteases examined, there are a set of preferred, but not required, properties that can be reliably observed only by aligning the sites and comparing them with carefully selected statistical controls.

Animals↗

PubMed1995

Characterizing the microenvironment surrounding protein sites.

Sites are microenvironments within a biomolecular structure, distinguished by their structural or functional role. A site can be defined by a three-dimensional location and a local neighborhood around this location in which the structure or function exists. We have developed a computer system to facilitate structural analysis (both qualitative and quantitative) of biomolecular sites. Our system automatically examines the spatial distributions of biophysical and biochemical properties, and reports those regions within a site where the distribution of these properties differs significantly from control nonsites. The properties range from simple atom-based characteristics such as charge to polypeptide-based characteristics such as type of secondary structure. Our analysis of sites uses non-sites as controls, providing a baseline for the quantitative assessment of the significance of the features that are uncovered. In this paper, we use radial distributions of properties to study three well-known sites (the binding sites for calcium, the milieu of disulfide bridges, and the serine protease active site). We demonstrate that the system automatically finds many of the previously described features of these sites and augments these features with some new details. In some cases, we cannot confirm the statistical significance of previously reported features. Our results demonstrate that analysis of protein structure is sensitive to assumptions about background distributions, and that these distributions should be considered explicitly during structural analyses.

Binding Sites↗

PubMed1995

Characterizing oriented protein structural sites using biochemical properties.

A protein site is a region of a three-dimensional protein structure with a distinguishing functional or structural role. Certain sites recur in different protein structures (for example catalytic sites, calcium binding sites, and some types of turns), but maintain critical shared features. To facilitate the analysis of such protein sites, we have developed a computer system for analyzing the spatial distributions of biochemical properties around a site. The system takes a set of similar sites and a set of control nonsites, and finds differences between them. Specifically, it compares distributions of the properties surrounding the sites with those surrounding the nonsites, and reports statistically significant differences. In this paper, we use our method to analyze the features in the active site of the serine protease enzymes. We compare the use of radial distributions (shells) with 3-D grids (blocks) in the analysis of the active site. We demonstrate three different strategies for focusing attention on significant findings, based on properties of interest, spatial volumes of interest, and on the level of statistical significance. Finally, we show that the program automatically identifies conserved sequential, secondary structural and biophysical features of the serine protease active site, using noncatalytic histidine residues as a control environment.

Algorithms↗