Powerful regression-based quantitative-trait linkage analysis of general pedigrees.
(65/910)
We present a new method of quantitative-trait linkage analysis that combines the simplicity and robustness of regression-based methods and the generality and greater power of variance-components models. The new method is based on a regression of estimated identity-by-descent (IBD) sharing between relative pairs on the squared sums and squared differences of trait values of the relative pairs. The method is applicable to pedigrees of arbitrary structure and to pedigrees selected on the basis of trait value, provided that population parameters of the trait distribution can be correctly specified. Ambiguous IBD sharing (due to incomplete marker information) can be accommodated in the method by appropriate specification of the variance-covariance matrix of IBD sharing between relative pairs. We have implemented this regression-based method and have performed simulation studies to assess, under a range of conditions, estimation accuracy, type I error rate, and power. For normally distributed traits and in large samples, the method is found to give the correct type I error rate and an unbiased estimate of the proportion of trait variance accounted for by the additive effects of the locus-although, in cases where asymptotic theory is doubtful, significance levels should be checked by simulations. In large sibships, the new method is slightly more powerful than variance-components models. The proposed method provides a practical and powerful tool for the linkage analysis of quantitative traits. (+info)
PATIKA: an integrated visual environment for collaborative construction and analysis of cellular pathways.
(66/910)
MOTIVATION: Availability of the sequences of entire genomes shifts the scientific curiosity towards the identification of function of the genomes in large scale as in genome studies. In the near future, data produced about cellular processes at molecular level will accumulate with an accelerating rate as a result of proteomics studies. In this regard, it is essential to develop tools for storing, integrating, accessing, and analyzing this data effectively. RESULTS: We define an ontology for a comprehensive representation of cellular events. The ontology presented here enables integration of fragmented or incomplete pathway information and supports manipulation and incorporation of the stored data, as well as multiple levels of abstraction. Based on this ontology, we present the architecture of an integrated environment named Patika (Pathway Analysis Tool for Integration and Knowledge Acquisition). Patika is composed of a server-side, scalable, object-oriented database and client-side editors to provide an integrated, multi-user environment for visualizing and manipulating network of cellular events. This tool features automated pathway layout, functional computation support, advanced querying and a user-friendly graphical interface. We expect that Patika will be a valuable tool for rapid knowledge acquisition, microarray generated large-scale data interpretation, disease gene identification, and drug development. AVAILABILITY: A prototype of Patika is available upon request from the authors. (+info)
PRIMROSE: a computer program for generating and estimating the phylogenetic range of 16S rRNA oligonucleotide probes and primers in conjunction with the RDP-II database.
(67/910)
We describe PRIMROSE, a computer program for identifying 16S rRNA probes and PCR primers for use as phylogenetic and ecological tools in the identification and enumeration of bacteria. PRIMROSE is designed to use data from the Ribosomal Database Project (RDP) to find potentially useful oligonucleotides with up to two degenerate positions. The taxonomic range of these, and other existing oligonucleotides, can then be explored, allowing for the rapid identification of suitable oligonucleotides. PRIMROSE includes features to allow user-defined sequence databases to be used. An in silico trial of the program using the RDP database identified oligonucleotides that described their target taxa with a degree of accuracy far greater than that of equivalent currently used oligonucleotides. We identify oligonucleotides for subdivisions of the Proteobacteria and for the Cytophaga-Flexibacter-Bacteroides (CFB) division. These oligonucleotides describe up to 94.7% of their target taxon with fewer than 50 non-target hits, and the authors recommend that they be investigated further. A comparison with PROBE DESIGN within the ARB software package shows that PRIMROSE is capable of identifying oligonucleotides with a higher specificity. PRIMROSE has an intuitive graphical user interface and runs on the Microsoft Windows 95/NT/2000 operating systems. It is open source and is freely available from the authors. (+info)
Simplifying amino acid alphabets by means of a branch and bound algorithm and substitution matrices.
(68/910)
MOTIVATION: Protein and DNA are generally represented by sequences of letters. In a number of circumstances simplified alphabets (where one or more letters would be represented by the same symbol) have proved their potential utility in several fields of bioinformatics including searching for patterns occurring at an unexpected rate, studying protein folding and finding consensus sequences in multiple alignments. The main issue addressed in this paper is the possibility of finding a general approach that would allow an exhaustive analysis of all the possible simplified alphabets, using substitution matrices like PAM and BLOSUM as a measure for scoring. RESULTS: The computational approach presented in this paper has led to a computer program called AlphaSimp (Alphabet Simplifier) that can perform an exhaustive analysis of the possible simplified amino acid alphabets, using a branch and bound algorithm together with standard or user-defined substitution matrices. The program returns a ranked list of the highest-scoring simplified alphabets. When the extent of the simplification is limited and the simplified alphabets are maintained above ten symbols the program is able to complete the analysis in minutes or even seconds on a personal computer. However, the performance becomes worse, taking up to several hours, for highly simplified alphabets. AVAILABILITY: AlphaSimp and other accessory programs are available at http://bioinformatics.cribi.unipd.it/alphasimp (+info)
Routine pulse oximetry in the asymptomatic newborn.
(69/910)
OBJECTIVE: To assess the effect of routine measurement of postductal oxygen saturation as an adjunct to routine clinical examination in the asymptomatic newborn. DESIGN AND SETTING: Prospective study in a district general hospital. PATIENTS: All 6166 infants inborn between 1 April 1999 and 31 March 2001. INTERVENTION: Oxygen saturation was measured over two minutes, after the age of 2 hours and before discharge, in one foot of all babies not admitted directly to the neonatal unit. Babies with fractional (as opposed to functional) oxygen saturation (SaO(2)) below 95% were examined by the midwife. If this examination was abnormal or if normal but further measurements were below 95%, an echocardiogram was performed. All babies with cardiac malformations diagnosed by 1 year of age were identified from databases maintained at the regional cardiology referral unit and the regional congenital malformation survey. RESULTS: Measurements were made in 98% of eligible babies. A fractional SaO(2) less than 95% was found in 5% but persisted in only 1%. Structural cardiac malformations were found in 50 (8.1/1000), 26 of whom had isolated ventricular septal defects. Of the remaining 24 with other cardiac malformations, attention was first drawn to six by low SaO(2), and four more, first noticed for other reasons, also had low SaO(2). Low SaO(2) also first drew attention to 13 other babies ill for other reasons. CONCLUSION: Newborn babies with important cardiac malformations are often asymptomatic initially and the yield from clinical examination is poor. Measuring postductal saturation routinely in newborn babies before discharge is easy and can alert staff to ill babies. (+info)
A collaborative program between a school of public health and a local health department to increase HIV testing of pregnant women.
(70/910)
OBJECTIVE: This study evaluates the effectiveness of a continuing medical education (CME) program that sought to increase HIV testing of women attending maternity clinics of the City of Houston Department of Health and Human Services (HDHHS). The CME program consisted of 14 training sessions given in 1995, 1996, 1997, 1999, and 2000. Educational objectives included increasing patient knowledge of HIV perinatal testing, increasing patient appreciation of the importance of HIV testing, and developing staff skills in educating and counseling women to accept HIV testing during pregnancy. METHODS: The CME program was based on assessment of clinician learning needs and an algorithm of the testing process, both jointly developed by faculty from the University of Texas Health Science Center at Houston School of Public Health and HDHHS personnel. The algorithm was also used to assess the care delivered. The CME was evaluated by examining changes in the percentage of women tested in the maternity clinics. RESULTS: In 1995, the year before the education program, 5.7% of women seen in the maternity clinics were tested for HIV. After the program began, testing rates rose to 64.2% in 1996, 65.5% in 1997, and 43.3% in 1998. Given the decline in testing in 1998, additional CME sessions were conducted in 1999-2000. The rate of testing rose to 62.3% in 1999 and 76.5% in 2000. CONCLUSION: Cooperative planning between university and health department personnel can create CME programs that alter provider behaviors and service delivery patterns to increase HIV testing. Outcomes need to be regularly monitored, however, to determine the need for maintenance or performance reinforcement. (+info)
Virtual reality-augmented rehabilitation for patients following stroke.
(71/910)
BACKGROUND AND PURPOSE: Recent evidence indicates that intensive massed practice may be necessary to modify neural organization and effect recovery of motor skills in patients following stroke. Virtual reality (VR) technology has the capability of creating an interactive, motivating environment in which practice intensity and feedback can be manipulated to create individualized treatments to retrain movement. CASE DESCRIPTION: Three patients (ML, LE, and DK), who were in the chronic phase following stroke, participated in a 2-week training program (3 1/2 hours a day) including dexterity tasks on real objects and VR exercises. The VR simulations were targeted for range of motion, movement speed, fractionation, and force production. OUTCOMES: ML's function was the most impaired at the beginning of the intervention, but showed improvement in the thumb and fingers in range of motion and speed of movement. LE improved in fractionation and range of motion of his thumb and fingers. DK made the greatest gains, showing improvement in range of motion and strength of the thumb, velocity of the thumb and fingers, and fractionation. Two of the 3 patients improved on the Jebsen Test of Hand Function. DISCUSSION: The outcomes suggest that VR may be useful to augment rehabilitation of the upper limb in patients in the chronic phase following stroke. (+info)
The Bioperl toolkit: Perl modules for the life sciences.
(72/910)
The Bioperl project is an international open-source collaboration of biologists, bioinformaticians, and computer scientists that has evolved over the past 7 yr into the most comprehensive library of Perl modules available for managing and manipulating life-science information. Bioperl provides an easy-to-use, stable, and consistent programming interface for bioinformatics application programmers. The Bioperl modules have been successfully and repeatedly used to reduce otherwise complex tasks to only a few lines of code. The Bioperl object model has been proven to be flexible enough to support enterprise-level applications such as EnsEMBL, while maintaining an easy learning curve for novice Perl programmers. Bioperl is capable of executing analyses and processing results from programs such as BLAST, ClustalW, or the EMBOSS suite. Interoperation with modules written in Python and Java is supported through the evolving BioCORBA bridge. Bioperl provides access to data stores such as GenBank and SwissProt via a flexible series of sequence input/output modules, and to the emerging common sequence data storage format of the Open Bioinformatics Database Access project. This study describes the overall architecture of the toolkit, the problem domains that it addresses, and gives specific examples of how the toolkit can be used to solve common life-sciences problems. We conclude with a discussion of how the open-source nature of the project has contributed to the development effort. (+info)