Physical Sciences and Mathematics Commons^™

Multiple Loci Within The Major Histocompatibility Complex Confer Risk Of Psoriasis, Bing-Jian Feng, Liang-Dan Sun, Razieh Soltani-Arabshahi, Anne M. Bowcock, Rajan P. Nair, Philip Stuart, James T. Elder, Steven J. Schrodi, Ann B. Begovich, Goncalo R. Abecasis, Xue-Jun Zhang, Kristina P. Callis Duffin, Gerald G. Krueger, David E. Goldgar

Steven J Schrodi

Psoriasis is a common inflammatory skin disease characterized by thickened scaly red plaques. Previously we have performed a genome-wide association study (GWAS) on psoriasis with 1,359 cases and 1,400 controls, which were genotyped for 447,249 SNPs. The most significant finding was for SNP rs12191877, which is in tight linkage disequilibrium with HLA-Cw*0602, the consensus risk allele for psoriasis. However, it is not known whether there are other psoriasis loci within the MHC in addition to HLA-C. In the present study, we searched for additional susceptibility loci within the human leukocyte antigen (HLA) region through in-depth analyses of the GWAS data; …

Regression When The Predictors Are Images, Philip T. Reiss

Philip T. Reiss

No abstract provided.

Smoothing Parameter Selection For A Class Of Semiparametric Linear Models, Philip T. Reiss, R. Todd Ogden

Philip T. Reiss

Spline-based approaches to nonparametric and semiparametric regression, as well as to regression of scalar outcomes on functional predictors, entail choosing a parameter controlling the extent to which roughness of the fitted function is penalized. In this paper we demonstrate that the equations determining two popular methods for smoothing parameter selection, generalized cross-validation and restricted maximum likelihood, share a similar form that allows us to prove several results common to both, and to derive a condition under which they yield identical values. These ideas are illustrated by application of functional principal component regression, a method for regressing scalars on functions, to …

Alamethicin In Lipid Bilayers: Combined Use Of X-Ray Scattering And Md Simulations, Jianjun Pan, D. Peter Tieleman, John F. Nagle, Norbert Kučerka, Prof. Stephanie Tristram-Nagle Ph.D.

Prof. Stephanie Tristram-Nagle Ph.D.

We study fully hydrated bilayers of two di-monounsaturated phospholipids diC18:1PC (DOPC) and diC22:1PC with varying amounts of alamethicin (Alm). We combine the use of X-ray diffuse scattering and molecular dynamics simulations to determine the orientation of alamethicin in model lipids. Comparison of the experimental and simulated form factors shows that Alm helices are inserted transmembrane at high humidity and high concentrations, in agreement with earlier results. The X-ray scattering data and the MD simulations agree that membrane thickness changes very little up to 1/10 Alm/ DOPC. In contrast, the X-ray data indicate that the thicker diC22:1PC membrane thins with added …

Evaluation Of Heterogeneity In Pharmacotherapy Trials For Drug Dependence: A Bayesian Approach, Charles E. Green, F. G. Moeller, J. M. Schmitz, Joseph F. Lucke, S. D. Lane, A. C. Swann, Robert E. Lasky, Joseph P. Carbonari

Joseph Lucke

Difficulty identifying effective pharmacotherapies for cocaine dependence has led to suggestions that subgroup differences may account for some of the heterogeneity in treatment response. Well-attested methodologicalifficulties associated with these analyses recommend the use of Bayesian statistical reasoning for evaluation of salient interaction effects.

Methods: A secondary data analysis of a previously published, double-blind, randomized controlled trial examines the interaction of decision-making, as measured by the Iowa Gambling Task, and citalopram in increasing longest sustained abstinence from cocaine use.

Results: Bayesian analysis indicated that there was a 99% chance that improved decision-making enhances response to citalopram. Given the strong positive nature …

When To Spray: A Time-Scale Calculus Approach To Controlling The Impact Of West Nile Virus, Diana Thomas, Marion Weedermann, Lora Billings, Joan Hoffacker, Robert A. Washington-Allen

Lora Billings

Should Biomarker Estimates Of Hiv Incidence Be Adjusted?, Ron Brookmeyer

Ron Brookmeyer

Objective: To evaluate adjustment procedures that have been proposed to correct HIV incidence rates derived from cross-sectional surveys of biomarkers (BED). These procedures were motivated by some reports that the biomarker BED approach overestimates incidence when compared to cohort studies.

Design: Considered the Hargrove and McDougal adjustment procedures that adjust biomarker estimates of HIV incidence rates for misclassification with respect to the timing of infections.

Methods: Performed mathematical and statistical analysis of the adjustment formulas. Evaluated sources of error in cohort studies of incidence that could also explain discrepancies between cohort and biomarker estimates.

Results: The McDougal adjustment has no …

The Effects Of Herd Immunity On The Power Of Vaccine Trials, Blake Charvat, Ron Brookmeyer, Jay Herson

Ron Brookmeyer

We evaluate the effects of herd immunity on the power of vaccine trials. We consider large-scale trials in which persons are individually randomized to either placebo or vaccine. We evaluate the adequacy of naive power calculations that ignore the effects of herd immunity such as those based on the comparison of two independent binomials. We developed a simulation design to evaluate the quantitative effects of herd immunity on power. The simulation design accounted for nonhomogeneous mixing. We found that naive power calculations that ignore the effects of herd immunity can seriously overestimate power. In fact, we found that as sample …

Genome-Wide Scan Reveals Association Of Psoriasis With Il-23 And Nf-B Pathways, Rajan P. Nair, Kristina C. Duffin, Cynthia Helms, Jun Ding, Philip E. Stuart, David Goldgar, Johann E. Gudjonsson, Yun Li, Trilokraj Tejasvi, Bing-Jiag Feng, Andreas Ruether, Stefan Schreiber, Michael Weichenthal, Dafna Gladman, Proton Rahman, Steven J. Schrodi, Sampath Prahalad, Stephen L. Guthery, Judith Fischer, Wilson Liao, Pui-Yan Kwok, Alan Menter, G Mark Lathrop, Carol A. Wise, Ann B. Begovich, John J. Voorhees, James T. Elder, Gerald G. Krueger, Anne M. Bowcock, Goncalo R. Abecasis

Steven J Schrodi

Psoriasis is a common immune-mediated disorder that affects the skin, nails and joints. To identify psoriasis susceptibility loci, we genotyped 438,670 SNPs in 1,409 psoriasis cases and 1,436 controls of European ancestry. We followed up 21 promising SNPs in 5,048 psoriasis cases and 5,041 controls. Our results provide strong support for the association of at least seven genetic loci and psoriasis (each with combined P < 5 10-8). Loci with confirmed association include HLA-C, three genes involved in IL-23 signaling (IL23A, IL23R, IL12B), two genes that act downstream of TNF- and regulate NF-B signaling (TNIP1, TNFAIP3) and two genes involved in the modulation of Th2 immune responses (IL4, IL13). Although the proteins encoded in these loci are known to interact biologically, we found no evidence for epistasis between associated SNPs. Our results expand the catalog of genetic loci implicated in psoriasis susceptibility and suggest priority targets for study in other auto-immune disorders.

A Fine Mapping Theorem To Refine Results From Association Genetics Studies, Steven J. Schrodi

Steven J Schrodi

No abstract provided.

Bayesian Statistics, Joseph F. Lucke

Joseph Lucke

No abstract provided.

Characterization Of Unknown Genetic Modifications Using High Throughput Sequencing And Computational Subtraction, Torstein Tengs

Dr. Torstein Tengs

Background

When generating a genetically modified organism (GMO), the primary goal is to give a target organism one or several novel traits by using biotechnology techniques. A GMO will differ from its parental strain in that its pool of transcripts will be altered. Currently, there are no methods that are reliably able to determine if an organism has been genetically altered if the nature of the modification is unknown.

Results

We show that the concept of computational subtraction can be used to identify transgenic cDNA sequences from genetically modified plants. Our datasets include 454-type sequences from a transgenic line of …