Biomedical subjects

Jonathan A Barker

Publications and source records attributed to Jonathan A Barker.

3 recordsLinked to original sources

PubMed2003

An algorithm for constraint-based structural template matching: application to 3D templates with statistical analysis.

MOTIVATION: Structural templates consisting of a few atoms in a specific geometric conformation provide a powerful tool for studying the relationship between protein structure and function. Current methods for template searching constrain template syntax and semantics by their design. Hence there is a need for a more flexible core algorithm upon which to build more sophisticated tools. Statistical analysis of structural similarity is still in its infancy when compared with its analogue in sequence alignment. In the context of template matching, there is an urgent need for normalization of scores so that results from templates with differing sensitivity may be compared directly. RESULTS: We introduce Jess, a fast and flexible algorithm for searching protein structures for small groups of atoms under arbitrary constraints on geometry and chemistry. We apply the algorithm to a set of manually derived enzyme active site templates, and derive an empirical measure for estimating the relative significance of hits encountered using differing templates.

Algorithms↗

PubMed2003

Using structural motif templates to identify proteins with DNA binding function.

This work describes a method for predicting DNA binding function from structure using 3-dimensional templates. Proteins that bind DNA using small contiguous helix-turn-helix (HTH) motifs comprise a significant number of all DNA-binding proteins. A structural template library of seven HTH motifs has been created from non-homologous DNA-binding proteins in the Protein Data Bank. The templates were used to scan complete protein structures using an algorithm that calculated the root mean squared deviation (rmsd) for the optimal superposition of each template on each structure, based on C(alpha) backbone coordinates. Distributions of rmsd values for known HTH-containing proteins (true hits) and non-HTH proteins (false hits) were calculated. A threshold value of 1.6 A rmsd was selected that gave a true hit rate of 88.4% and a false positive rate of 0.7%. The false positive rate was further reduced to 0.5% by introducing an accessible surface area threshold value of 990 A2 per HTH motif. The template library and the validated thresholds were used to make predictions for target proteins from a structural genomics project.

Algorithms↗

PubMed2003

Celiac artery compression by the median arcuate ligament: a pitfall of end-expiratory MR imaging.

PURPOSE: To measure the prevalence and degree of celiac artery compression during breath-hold imaging at end inspiration and end expiration in patients referred to undergo magnetic resonance (MR) imaging of the abdomen for reasons unrelated to intestinal ischemia. MATERIALS AND METHODS: A series of 100 patients underwent routine MR imaging of the upper abdomen at 1.5 T; imaging included multiple dynamic contrast-enhanced fat-suppressed transverse three-dimensional spoiled gradient-echo acquisitions (3.6-4.5/1.5-1.9 [repetition time msec/echo time msec], 12 degrees flip angle). Arterial phase acquisitions were obtained during suspended respiration at end expiration (n = 50) or at end inspiration (n = 50), and venous phase acquisitions were obtained at the opposite respiratory phase. Two radiologists, blinded to patient identity and the phase of respiration, independently assessed the degree of narrowing on reconstructed oblique sagittal images. Radiologists reached consensus in 97 patients, who formed the cohort for this study. The percentage of stenosis of the celiac artery relative to its origin and the angle formed by the proximal celiac artery and the aorta were also measured in all patients. This angle and the arcsine transformation of the percentage of stenosis were compared for the two respiratory phases by using a paired Student t test. chi2 analysis was used to evaluate whether the degree of narrowing was independent of the breath-hold protocol that was used. RESULTS: In total, 55 (57%) of 97 patients had at least mild artery narrowing at end expiration, of whom 40 (73%) had less narrowing at end inspiration and 11 (20%) had no change. The average percentage of stenosis at end expiration (21% +/- 16) was significantly higher than that at end inspiration (11% +/- 11; P <.001). At end expiration, the average celiac artery angle was significantly lower in patients with mild to severe narrowing (41 degrees +/- 19) than in those without narrowing (50 degrees +/- 19; P <.03). CONCLUSION: Accentuation of celiac artery compression at end expiration can give rise to a potential pitfall of breath-hold abdominal imaging. When compression is suspected, imaging should be performed during inspiration.

Celiac Artery↗