Robert Shields

In Silico Gene Prioritization by Integrating Multiple Data Sources

Identifying disease genes is crucial to the understanding of disease pathogenesis, and to the improvement of disease diagnosis and treatment. In recent years, many researchers have proposed approaches to prioritize candidate genes by considering the relationship of candidate genes and existing known disease genes, reflected in other data sources. In this paper, we propose an expandable framework for gene prioritization that can integrate multiple heterogeneous data sources by taking advantage of a unified graphic representation. Gene-gene relationships and gene-disease relationships are then defined based on the overall topology of each network using a diffusion kernel measure. These relationship measures are in turn normalized to derive an overall measure across all networks, which is utilized to rank all candidate genes. Based on the informativeness of available data sources with respect to each specific disease, we also propose an adaptive threshold score to select a small subset of candidate genes for further validation studies. We performed large scale cross-validation analysis on 110 disease families using three data sources. Results have shown that our approach consistently outperforms other two state of the art programs. A case study using Parkinson disease (PD) has identified four candidate genes (UBB, SEPT5, GPR37 and TH) that ranked higher than our adaptive threshold, all of which are involved in the PD pathway. In particular, a very recent study has observed a deletion of TH in a patient with PD, which supports the importance of the TH gene in PD pathogenesis. A web tool has been implemented to assist scientists in their genetic studies.

Scintigraphic measurement of oropharyngeal transit in man

Scintigraphic studies of the oropharyngeal transit of a liquid bolus were performed in 15 healthy controls, 12 patients with symptoms of oral-pharyngeal dysphagia, and 13 patients with neuromuscular disease, who did not have dysphagia. Gamma camera imaging of the head, neck, and upper thorax was undertaken, in the lateral projection, during the swallowing of the radiolabeled bolus of water. Inspection of summed images permitted the selection of regions of interest (ROI) to represent the mouth, pharynx, and upper esophagus. Transit times between each ROI were calculated and compared. Significant prolongation of bolus transit time between the mouth and esophagus was present in both patients with and without dysphagia (0.59 ± 0.38 sec and 0.33 ± 0.7 sec; mean ± SD, respectively) compared with controls (0.26 ± 0.04 sec P < 0.001, P < 0.01, respectively, Mann-Whitney U test). Repeat studies in 25 individuals indicated that the transit measurements were more reproducible between swallows in normal subjects than in patients with symptoms. Deglutitive scintigraphy provides a noninvasive technique for the quantitative study of swallowing and its disorders.

Congenital Vascular Abnormalities in Okihiro's Syndrome— A Case Report

In this report, the authors describe the angiographic findings in the forearm and hand in Okihiros syndrome. To the best of their knowledge, it has not been described before. Okihiro et al described hypoplasia of the thenar eminence in association with a congenital disorder of ocular motility previously reported in Duanes syn drome.

Vascular insufficiency in Okihiro's syndrome secondary to hypothenar hammer syndrome

The presence of Okihiros syndrome (congenital thenar hypoplasia and Duanes anomaly) in a patient became clinically significant when a hypothenar hammer syndrome developed. The ulnar artery occlusion resulted in a compromise of the hands vascular supply because of a congenital hypoplastic radial artery. Resection of the thrombosed ulnar artery and insertion of an interposition vein graft restored circulation to the hand. Anatomic features in this case include a hypoplastic radial artery and double motor branch of the median nerve. Clinicians should consider Okihiros syndrome in the differential diagnosis of thenar muscle atrophy since there are genetic, diagnostic, and clinical implications.

CT demonstration of brain infarcts due to deep venous thrombosis in systemic lupus erythematosus.

Rapid development of low density bilateral lesions in the brain due to deep venous thrombosis in Systemic Lupus Erythematosis is described. To the best of our knowledge, this type of symmetry, distribution and appearance of brain infarcts in CT due to deep venous thrombosis has not been reported previously.

Joint analysis of sequence data and single-nucleotide polymorphism data using pedigree information for imputation and recombination inference

We developed a general framework for family-based imputation using single-nucleotide polymorphism data and sequence data distributed by Genetic Analysis Workshop 18. By using PedIBD, we first inferred haplotypes and inheritance patterns of each family from SNP data. Then new variants in unsequenced family members can be obtained from sequenced relatives through their shared haplotypes. We then compared the results of our method against the imputation results provided by Genetic Analysis Workshop organizers. The results showed that our strategy uncovered more variants for more unsequenced relatives. We also showed that recombination breakpoints inferred by PedIBD have much higher resolution than those inferred from previous studies.