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At least 955 records · Page 53Linked to original sources
PubMed2003

MHCPred: A server for quantitative prediction of peptide-MHC binding.

Accurate T-cell epitope prediction is a principal objective of computational vaccinology. As a service to the immunology and vaccinology communities at large, we have implemented, as a server on the World Wide Web, a partial least squares-based multivariate statistical approach to the quantitative prediction of peptide binding to major histocom- patibility complexes (MHC), the key checkpoint on the antigen presentation pathway within adaptive cellular immunity. MHCPred implements robust statistical models for both Class I alleles (HLA-A*0101, HLA-A*0201, HLA-A*0202, HLA-A*0203, HLA-A*0206, HLA-A*0301, HLA-A*1101, HLA-A*3301, HLA-A*6801, HLA-A*6802 and HLA-B*3501) and Class II alleles (HLA-DRB*0401, HLA-DRB*0401 and HLA-DRB*0701). MHCPred is available from the URL: http://www.jenner.ac.uk/MHCPred.

Binding Sites↗
PubMed2003

WebFEATURE: An interactive web tool for identifying and visualizing functional sites on macromolecular structures.

WebFEATURE (http://feature.stanford.edu/webfeature/) is a web-accessible structural analysis tool that allows users to scan query structures for functional sites in both proteins and nucleic acids. WebFEATURE is the public interface to the scanning algorithm of the FEATURE package, a supervised learning algorithm for creating and identifying 3D, physicochemical motifs in molecular structures. Given an input structure or Protein Data Bank identifier (PDB ID), and a statistical model of a functional site, WebFEATURE will return rank-scored 'hits' in 3D space that identify regions in the structure where similar distributions of physicochemical properties occur relative to the site model. Users can visualize and interactively manipulate scored hits and the query structure in web browsers that support the Chime plug-in. Alternatively, results can be downloaded and visualized through other freely available molecular modeling tools, like RasMol, PyMOL and Chimera. A major application of WebFEATURE is in rapid annotation of function to structures in the context of structural genomics.

Algorithms↗
PubMed2004

Identifying estrogen receptor alpha target genes using integrated computational genomics and chromatin immunoprecipitation microarray.

The estrogen receptor alpha (ERalpha) regulates gene expression by either direct binding to estrogen response elements or indirect tethering to other transcription factors on promoter targets. To identify these promoter sequences, we conducted a genome-wide screening with a novel microarray technique called ChIP-on-chip. A set of 70 candidate ERalpha loci were identified and the corresponding promoter sequences were analyzed by statistical pattern recognition and comparative genomics approaches. We found mouse counterparts for 63 of these loci and classified 42 (67%) as direct ERalpha targets using classification and regression tree (CART) statistical model, which involves position weight matrix and human-mouse sequence similarity scores as model parameters. The remaining genes were considered to be indirect targets. To validate this computational prediction, we conducted an additional ChIP-on-chip assay that identified acetylated chromatin components in active ERalpha promoters. Of the 27 loci upregulated in an ERalpha-positive breast cancer cell line, 20 having mouse counterparts were correctly predicted by CART. This integrated approach, therefore, sets a paradigm in which the iterative process of model refinement and experimental verification will continue until an accurate prediction of promoter target sequences is derived.

Animals↗
PubMed2004

Solving the riddle of codon usage preferences: a test for translational selection.

Translational selection is responsible for the unequal usage of synonymous codons in protein coding genes in a wide variety of organisms. It is one of the most subtle and pervasive forces of molecular evolution, yet, establishing the underlying causes for its idiosyncratic behaviour across living kingdoms has proven elusive to researchers over the past 20 years. In this study, a statistical model for measuring translational selection in any given genome is developed, and the test is applied to 126 fully sequenced genomes, ranging from archaea to eukaryotes. It is shown that tRNA gene redundancy and genome size are interacting forces that ultimately determine the action of translational selection, and that an optimal genome size exists for which this kind of selection is maximal. Accordingly, genome size also presents upper and lower boundaries beyond which selection on codon usage is not possible. We propose a model where the coevolution of genome size and tRNA genes explains the observed patterns in translational selection in all living organisms. This model finally unifies our understanding of codon usage across prokaryotes and eukaryotes. Helicobacter pylori, Saccharomyces cerevisiae and Homo sapiens are codon usage paradigms that can be better understood under the proposed model.

Animals↗
PubMed2005

WordSpy: identifying transcription factor binding motifs by building a dictionary and learning a grammar.

Transcription factor (TF) binding sites or motifs (TFBMs) are functional cis-regulatory DNA sequences that play an essential role in gene transcriptional regulation. Although many experimental and computational methods have been developed, finding TFBMs remains a challenging problem. We propose and develop a novel dictionary based motif finding algorithm, which we call WordSpy. One significant feature of WordSpy is the combination of a word counting method and a statistical model which consists of a dictionary of motifs and a grammar specifying their usage. The algorithm is suitable for genome-wide motif finding; it is capable of discovering hundreds of motifs from a large set of promoters in a single run. We further enhance WordSpy by applying gene expression information to separate true TFBMs from spurious ones, and by incorporating negative sequences to identify discriminative motifs. In addition, we also use randomly selected promoters from the genome to evaluate the significance of the discovered motifs. The output from WordSpy consists of an ordered list of putative motifs and a set of regulatory sequences with motif binding sites highlighted. The web server of WordSpy is available at http://cic.cs.wustl.edu/wordspy.

Algorithms↗
PubMed2005

miBLAST: scalable evaluation of a batch of nucleotide sequence queries with BLAST.

A common task in many modern bioinformatics applications is to match a set of nucleotide query sequences against a large sequence dataset. Existing tools, such as BLAST, are designed to evaluate a single query at a time and can be unacceptably slow when the number of sequences in the query set is large. In this paper, we present a new algorithm, called miBLAST, that evaluates such batch workloads efficiently. At the core, miBLAST employs a q-gram filtering and an index join for efficiently detecting similarity between the query sequences and database sequences. This set-oriented technique, which indexes both the query and the database sets, results in substantial performance improvements over existing methods. Our results show that miBLAST is significantly faster than BLAST in many cases. For example, miBLAST aligned 247 965 oligonucleotide sequences in the Affymetrix probe set against the Human UniGene in 1.26 days, compared with 27.27 days with BLAST (an improvement by a factor of 22). The relative performance of miBLAST increases for larger word sizes; however, it decreases for longer queries. miBLAST employs the familiar BLAST statistical model and output format, guaranteeing the same accuracy as BLAST and facilitating a seamless transition for existing BLAST users.

Algorithms↗
PubMed2000

Familial aggregation of environmental risk factors and familial aggregation of disease.

Almost all human diseases have been shown to aggregate familially to some degree. This familiality is generally taken as evidence for the existence of a genetic etiologic mechanism or environmental factors common to family members, or a combination of both. It has been argued that for a disease with strong familial aggregation, environmental risk factors alone are unlikely to account for such strong aggregation, unless the presumed environmental risk factors are associated with enormous risk. This paper revisits this issue through the use of a novel statistical model. Ascertainment bias aside, the author demonstrates that familial aggregation could be explained by multiple interactive risk factors, each of which may confer a low disease risk and thus contribute only a minuscule portion to disease familiality. For example, two correlated risk factors (r=0.5), each with a relative risk of 5 and acting multiplicatively, could give rise to a sibling relative risk of 1.96. Therefore, it may not be sufficient to argue for a genetic component for a disease based solely on the notion that no high risk environmental factors have been found. In view of this, there is a need to examine carefully the roles of multiple environmental risk factors in disease familiality.

Bias↗
PubMed1990

A surveillance system for assessing health effects from hazardous exposures.

A statistical procedure for monitoring the health status of a community potentially exposed to a hazardous environment is presented. It utilizes two levels of investigation. Level I studies monitor routinely collected vital statistics and routes of community exposure whereas level II studies require additional data collection and are further distinguished by their design and duration. In a level I study, routine vital statistics for specified end points over a specified period of time are monitored, and the observed number of events is compared with the expected number of events for a given population. The statistical model used with this procedure employs a two-step decision rule based on the standardized mortality ratio for the study community. An "alert status" is invoked when the number of events exceeds a prescribed excess. An "action status" is indicated if the excess noted in the initial period persists or if the observed number of events in the initial period greatly exceeds expectation. Should an "action status" be justified, level II studies to determine the likely explanation for the significant excess are initiated. This could include the conduct of a "case-control" study using the exposure data available from monitoring the community.

Cluster Analysis↗
PubMed2004

Indoor radon concentration forecasting in South Tyrol.

In this paper a modern statistical technique of multivariate analysis is applied to an indoor radon concentration data base. Several parameters are more or less significant in determining the radon concentration inside a building. The elaboration of the information available on South Tyrol makes it possible both to identify the statistically significant variables and to build up a statistical model that allows us to forecast the radon concentration in dwellings, when the values of the same variables involved are given. The results confirm the complexity of the phenomenon.

Air Pollutants, Radioactive↗
PubMed2000

Statistical analysis of skin tumor data from Tg.AC mouse bioassays.

New strategies for identifying chemical carcinogens and assessing risk have been proposed based on the Tg.AC (zetaglobin promoted v-Ha-ras) transgenic mouse. Preliminary studies suggest that the Tg. AC mouse bioassay may be an effective means of quickly evaluating the carcinogenic potential of a test agent. The skin of the Tg.AC mouse is genetically initiated, and the induction of epidermal papillomas in response to dermal or oral exposure to a chemical agent acts as a reporter phenotype of the activity of the test chemical. In Tg.AC mouse bioassays, the test agent is typically applied topically for up to 26 weeks, and the number of papillomas in the treated area is counted weekly. Statistical analyses are complicated by within-animal and serial dependency in the papilloma counts, survival differences between animals, and missing data. In this paper, we describe a statistical model for the analysis of skin tumor data from a Tg.AC mouse bioassay. The model separates effects on papilloma latency and multiplicity and accommodates important features of the data, including variability in expression of the transgene and dependency in the tumor counts. Methods are described for carcinogenicity testing and risk assessment. We illustrate our approach using data from a study of the effect of 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD) exposure on tumorigenesis.

Administration, Topical↗
PubMed2000

Female gender associates with increased duration of intubation and length of stay after coronary artery surgery. CABG Clinical Benchmarking Database Participants.

BACKGROUND: Females have worse outcome than do males after coronary artery bypass grafting; however, gender effects on length of stay (LOS) outcomes, such as duration of intubation or intensive care unit (ICU) LOS, have not been evaluated previously. The authors hypothesized that adjustment for pertinent preoperative covariates would eliminate any significant effect of gender on duration of intubation, LOS in the ICU after extubation, total ICU LOS, postoperative (exclusive of ICU) LOS, or total postoperative LOS. METHODS: Patients undergoing elective or urgent primary coronary artery bypass grafting surgery at 51 academic health centers in 1995 and 1997 were studied. Unique multivariable statistical models were developed for duration of intubation, ICU LOS after extubation, total ICU LOS, and postoperative (exclusive of ICU and total) LOS to test for independent associations with gender. Preoperative but not intraoperative or postoperative variables were included in the model. P> or =0.01 was considered significant. RESULTS: All LOSs were of significantly longer duration in females than in males in both the 1995 (n = 1,064) and 1997 (n = 910) data collections. After covariate adjustment, female sex remained associated with significantly longer duration ICU LOS and total postoperative LOS in both the 1995 (female:male ratios 1.30:1 and 1.13:1, respectively) and the 1997 (female:male ratios 1.19:1 and 1.12:1, respectively) data sets. After covariate adjustment, duration of intubation and ICU LOS after extubation were of significantly longer duration in women than men in 1995 (female:male ratios 1.22:1 and 1.39:1, respectively), but the differences were not significant in 1997. CONCLUSIONS: Even in the context of accelerated recovery programs, these analyses show that female sex has powerful associations with increased LOS intervals for coronary artery bypass grafting surgery, even after adjustment for preoperative covariates. These effects could result from differences in the ways in which men and women respond to coronary artery disease, anesthesia, and coronary artery bypass grafting surgery, or to bias on the part of healthcare workers.

Aged↗
PubMed1990

Surveillance of AIDS in the European Community: recent trends and predictions to 1991.

Statistical modelling is applied to routine AIDS surveillance data to assess recent trends and to provide a range of short-term predictions. Several alternative functions have been fitted to half-yearly incidence data reported by the countries of the European Community by 31 December 1989 and adjusted for reporting delays. Among homosexual/bisexual men, recent trends in AIDS incidence are more nearly linear than exponential. Higher though less than exponential rates of growth are observed among intravenous drug users and among those presumed infected by heterosexual contact. Extrapolations to the end of 1991 using each of five functions provide a range of forecasts. Projections of total cumulated cases to the end of 1991 lie in the range 60,000-78,000, with 24,000-30,000 projected cases among homosexual/bisexual men, 23,000-33,000 among intravenous drug users, and 6000-8000 in the heterosexual transmission group. With the possible exception of the latter group, the lower parts of these ranges appear more probable.

Acquired Immunodeficiency Syndrome↗
PubMed2002

Private practicing endodontists: production of endodontic services and implications for workforce policy.

The methods and techniques used by private practicing endodontists to provide patient care are at the core of endodontic workforce policy. Productivity influences both the amount of care provided and the required number of practicing endodontists in the future. Data was collected from practicing endodontists in order to characterize the technical methods of producing endodontic services. This data was then used to develop a statistical model for use in assessing the national endodontic workforce conditions in the United States. A survey was mailed to a random sample of 2,075 private practicing endodontists in the United States based on membership files from the American Association of Endodontists and the American Dental Association. The overall survey consisted of three means of data collection: (1) a survey about the endodontic practice as a whole; (2) a survey about the endodontist; and (3) patient encounter forms used when collecting detailed endodontic procedure data for a single day in the practice. The model was used to obtain a projection of 4,016 endodontists in the year 2005 and 4,671 practicing endodontists in 2010 required to meet the projected demand for endodontic care. The model and survey data provide valuable information to practicing endodontists for use in identifying critical elements used to render care, how the elements are combined in the practice of endodontics, and the minimum number of endodontists required to provide a given volume of endodontic care.

Adult↗
PubMed1996

Helicobacter pylori and recurrent abdominal pain in children.

Recurrent abdominal pain is one of the most common presentations to pediatricians; yet an organic etiology can be found in only 10% of cases. Because infection with Helicobacter pylori in adults and children results in gastritis, a causative role for the organism has been postulated. To investigate this theory, we conducted a prospective case-control study in children with recurrent abdominal pain using serum H. pylori IgG antibodies measured by an enzyme immunoabsorbent assay. Age, sex, ethnicity, and socioeconomic status were adjusted in the statistical model. Five subjects (5.1%) and 14 controls (14.3%) had raised serum IgG antibodies to H. pylori (adjusted OR, 0.21; 95% confidence interval, 0.05, 0.85). The negative association between H. pylori and recurrent abdominal pain indicates that this organism is unlikely to have an important etiologic role in this disorder.

Abdominal Pain↗
PubMed2001

Motor vehicle crashes in New York State: importance of accounting for emergency department deaths when assessing differences in in-hospital mortality by level of care.

BACKGROUND: Motor vehicle crashes (MVCs) are one of the leading causes of death in the nation and in New York State, particularly among younger adult males. It is important to study how to reduce mortality from MVCs. METHODS: Hospitalized victims of motor vehicle crashes in the 1994-1995 New York State Trauma Registry were identified for the study. A statistical model was used to calculate risk-adjusted mortality rates for groups of hospitals constituting each level of care (regional trauma center, area trauma center, noncenter). Levels of care were also compared with respect to the location of deaths in the hospital (emergency department, inpatient), and the time between emergency department admission and death for patients dying in the hospital. RESULTS: The risk-adjusted mortality rate for MVCs in patients in regional centers was higher, although not significantly higher (6.91%; 95% confidence interval [CI], 6.18%-7.70%) than for area centers (5.53%; 95% CI, 4.43%-6.82%) or for noncenters (5.83%; 95% CI, 4.70%-7.15%). However, regional centers admitted seriously injured trauma patients from the emergency department much more quickly than other levels of care. Whereas only 18% of all in-hospital deaths occurred in emergency departments of regional centers, the comparable percentages for area centers and noncenters were 39% and 46%, respectively. Also, 43% of all deaths in regional centers occurred within 24 hours of presentation to the emergency department, compared with 15% in area centers and 21% in noncenters. CONCLUSION: Risk-adjusted inpatient mortality rates for victims of MVCs may not yield a fair comparison of performance for different levels of care or for different hospitals because of differences in how quickly emergency department patients are admitted to the hospital. A more equitable way to assess hospital mortality rates may be to include emergency department deaths in addition to inpatient deaths.

Accidents, Traffic↗
PubMed1995

Evaluating long-term care demonstrations in real time with study design and plan performance interactions.

The evaluation of long-term care demonstrations has to deal with complex organizational entities, with large, heterogeneous client populations that, during the course of study, may have to change features of their organization or operation. The implications of such "real-time" changes are discussed for analyses of the operation and performance of Social/Health Maintenance Organizations over a 5-year period (2 years of start-up and enrollment and 3 years of follow-up). Analyses conducted of the plans in the context of real-time changes have to be based on different statistical models than for classic experimental study designs, where treatment factors are fixed rather than dynamic. A number of issues that may arise are identified, and possible approaches to their solutions described. Key words: long-term care; demonstrations; evaluations; study design; capitation.

Activities of Daily Living↗
PubMed1996

Scaling peak VO2 for differences in body size.

This paper examined the influence of different statistical modeling techniques on the interpretation of peak VO2 data in groups of prepubertal, circumpubertal, and adult males (group 1M, N = 29; group 2M, N = 26; group 3M, N = 8) and females (group 1F, N = 33; group 2F, N = 34; group 3F, N = 16). Conventional comparisons of the simple per-body-mass ratio (ml.kg-1.min-1) revealed no significant differences between the three male groups (P < 0.05). In females, a decline in VO2 between group 2F and 3F was observed (P < 0.05). Both linear and log-linear (allometric) models revealed significant increases across all three male groups for peak VO2 adjusted for body mass (P < 0.05). In females these scaling models identified a significantly lower peak VO2 in group 1F versus groups 2F and 3F (P < 0.05). Based upon the common mass exponent identified (b = 0.80, SE = 0.04), power function ratios (y.mass0.80) were generated and the logarithms of these compared. Again, results indicated a progressive increase in peak VO2 across groups 1M to 3M (P < 0.05) and an increase between groups 1F and 2F (P < 0.05). Incorporating stature into the allometric equation reduced the mass exponent to 0.71 (SE = 0.06) with the contribution of the stature exponent shown to be 0.44 (SE = 0.20). These results indicate that conventional ratio standards do not adequately account for body size differences when investigating functional changes in peak VO2.

Adolescent↗