Biomedical subjects

Robert P Anderson

Publications and source records attributed to Robert P Anderson.

3 recordsLinked to original sources

PubMed2005

A systematic approach for comprehensive T-cell epitope discovery using peptide libraries.

MOTIVATION: T-cell response to peptides bound on MHC Class I or Class II molecules is essential for immune recognition of pathogens. T-cells are activated by specific peptide epitopes that are determined within the antigen processing pathways and presented on the surface of other cells bound to MHC molecules. To determine which part of allergenic or pathogenic proteins can stimulate T-cells is important for the treatment of diseases. We sought to take advantage of the falling cost of synthetic, screening grade peptides, and devise a comprehensive, non-hypothesis-driven screen for T-cell epitopes. We were interested in the study of celiac disease (CD) and used the ELISPOT technique to perform a large number of T-cell assays. We therefore needed to compensate for the lack of statistical data analysis methods for ELISPOT assays. RESULTS: We describe a method to comprehensively screen for T-cell epitopes within a family or a group of proteins. We have implemented an algorithm to generate a set of unique short peptide sequences that incorporate all possible epitopes within a group of proteins. T-cell assays were performed in 96-well plates using the ELISPOT assay to screen for responses in CD patients against any epitopes in glutens. We describe a statistical model to fit the data and an Expectation Maximization algorithm to estimate the parameters of interest and analyze the resulting data. AVAILABILITY: Implementations of our algorithms in R or Perl are available at http://bioinf.wehi.edu.au/folders/immunol.

Algorithms↗

PubMed2005

Coeliac disease.

BACKGROUND: Coeliac disease (CD) probably affects one in 100 Australians, but is greatly underdiagnosed. Heightened media interest in the negative effects of dietary gluten has led many patients to request testing for CD or follow inappropriate diets. Doctors have had little education in CD because of its perceived rarity. OBJECTIVE: This article summarises current knowledge of clinical presentations, optimal screening and diagnostic tests, and how the general practitioner can best assist patients in adopting a successful gluten free diet. DISCUSSION: Coeliac disease is associated with a range of conditions including type 1 diabetes, thyroid disease, osteoporosis, and iron deficiency with or without anaemia. Gastrointestinal symptoms may not be present. The GP therefore has an important role in considering CD in the differential diagnosis in a variety of clinical presentations. Antitransglutaminase IgA and total serum IgA are the preferred screening tests but may miss occasional patients with CD. Endoscopic duodenal biopsy while eating gluten is needed for definitive diagnosis. A gluten free diet is complex, and may fail without the involvement of a skilled dietician.

Biomarkers↗

PubMed2002

Dwarfism in insular sloths: biogeography, selection, and evolutionary rate.

The islands of Bocas del Toro, Panama, were sequentially separated from the adjacent mainland by rising sea levels during the past 10,000 years. Three-toed sloths (Bradypus) from five islands are smaller than their mainland counterparts, and the insular populations themselves vary in mean body size. We first examine relationships between body size and physical characteristics of the islands, testing hypotheses regarding optimal body size, evolutionary equilibria, and the presence of dispersal in this system. To do so, we conduct linear regressions of body size onto island area, distance from the mainland, and island age. Second, we retroactively calculate two measures of the evolutionary rate of change in body size (haldanes and darwins) and the standardized linear selection differential, or selection intensity (i). We also test the observed morphological changes against models of evolution by genetic drift. The results indicate that mean body size decreases linearly with island age, explaining up to 97% of the variation among population means. Neither island area nor distance from the mainland is significant in multiple regressions that include island age. Thus, we find no evidence for differential optimal body size among islands, or for dispersal in the system. In contrast, the dependence of body size on island age suggests uniform directional selection for small body size in the insular populations. Although genetic drift cannot be discounted as the cause for this evolution in body size, the probability is small given the consistent direction of evolution (repeated dwarfism). The insular sloths show a sustained rate of evolution similar to those measured in haldanes over tens of generations, appearing to unite micro- and macroevolutionary time scales. Furthermore, the magnitude and rate of this example of rapid differentiation fall within predictions of theoretical models from population genetics. However, the linearity of the relationship between body size and island age is not predicted, suggesting that either more factors are involved than those considered here, or that theoretical advances are necessary to explain constant evolutionary rates over long time spans in new selective environments.

Animals↗