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  1. Free, publicly-accessible full text available January 1, 2025
  2. Abstract

    Various polygenic risk scores (PRS) methods have been proposed to combine the estimated effects of single nucleotide polymorphisms (SNPs) to predict genetic risks for common diseases, using data collected from genome-wide association studies (GWAS). Some methods require external individual-level GWAS dataset for parameter tuning, posing privacy and security-related concerns. Leaving out partial data for parameter tuning can also reduce model prediction accuracy. In this article, we propose PRStuning, a method that tunes parameters for different PRS methods using GWAS summary statistics from the training data. PRStuning predicts the PRS performance with different parameters, and then selects the best-performing parameters. Because directly using training data effects tends to overestimate the performance in the testing data, we adopt an empirical Bayes approach to shrinking the predicted performance in accordance with the genetic architecture of the disease. Extensive simulations and real data applications demonstrate PRStuning’s accuracy across PRS methods and parameters.

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  3. Abstract

    Genetic association signals have been mostly found in noncoding regions through genome-wide association studies (GWAS), suggesting the roles of gene expression regulation in human diseases and traits. However, there has been limited success in colocalizing expression quantitative trait locus (eQTL) with disease-associated variants. Mediated expression score regression (MESC) is a recently proposed method to quantify the proportion of trait heritability mediated by genetically regulated gene expressions (GReX). Applications of MESC to GWAS results have yielded low estimation of mediated heritability for many traits. As MESC relies on stringent independence assumptions between cis-eQTL effects, gene effects, and nonmediated SNP effects, it may fail to characterize the true relationships between those effect sizes, which leads to biased results. Here, we consider the robustness of MESC to investigate whether the low fraction of mediated heritability inferred by MESC reflects biological reality for complex traits or is an underestimation caused by model misspecifications. Our results suggest that MESC may lead to biased estimates of mediated heritability with misspecification of gene annotations leading to underestimation, whereas misspecification of SNP annotations may lead to overestimation. Furthermore, errors in eQTL effect estimates may lead to underestimation of mediated heritability.

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  4. Free, publicly-accessible full text available November 1, 2024
  5. Abstract

    Contrary to topological insulators, topological semimetals possess a nontrivial chiral anomaly that leads to negative magnetoresistance and are hosts to both conductive bulk states and topological surface states with intriguing transport properties for spintronics. Here, we fabricate highly-ordered metallic Pt3Sn and Pt3SnxFe1-xthin films via sputtering technology. Systematic angular dependence (both in-plane and out-of-plane) study of magnetoresistance presents surprisingly robust quadratic and linear negative longitudinal magnetoresistance features for Pt3Sn and Pt3SnxFe1-x, respectively. We attribute the anomalous negative longitudinal magnetoresistance to the type-II Dirac semimetal phase (pristine Pt3Sn) and/or the formation of tunable Weyl semimetal phases through symmetry breaking processes, such as magnetic-atom doping, as confirmed by first-principles calculations. Furthermore, Pt3Sn and Pt3SnxFe1-xshow the promising performance for facilitating the development of advanced spin-orbit torque devices. These results extend our understanding of chiral anomaly of topological semimetals and can pave the way for exploring novel topological materials for spintronic devices.

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    Free, publicly-accessible full text available December 1, 2024
  6. Background While genomic variations can provide valuable information for health care and ancestry, the privacy of individual genomic data must be protected. Thus, a secure environment is desirable for a human DNA database such that the total data are queryable but not directly accessible to involved parties (eg, data hosts and hospitals) and that the query results are learned only by the user or authorized party. Objective In this study, we provide efficient and secure computations on panels of single nucleotide polymorphisms (SNPs) from genomic sequences as computed under the following set operations: union, intersection, set difference, and symmetric difference. Methods Using these operations, we can compute similarity metrics, such as the Jaccard similarity, which could allow querying a DNA database to find the same person and genetic relatives securely. We analyzed various security paradigms and show metrics for the protocols under several security assumptions, such as semihonest, malicious with honest majority, and malicious with a malicious majority. Results We show that our methods can be used practically on realistically sized data. Specifically, we can compute the Jaccard similarity of two genomes when considering sets of SNPs, each with 400,000 SNPs, in 2.16 seconds with the assumption of a malicious adversary in an honest majority and 0.36 seconds under a semihonest model. Conclusions Our methods may help adopt trusted environments for hosting individual genomic data with end-to-end data security. 
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  7. With the advances in autonomous vehicles and intelligent intersection management systems, traffic lights may be replaced by optimal travel plans calculated for each passing vehicle in the future. While these technological advancements are envisioned to greatly improve travel efficiency, they are still facing various challenging security hurdles since even a single deviation of a vehicle from its assigned travel plan could cause a serious accident if the surrounding vehicles do not take necessary actions in a timely manner. In this paper, we propose a novel security mechanism namely NWADE which can be integrated into existing autonomous intersection management systems to help detect malicious vehicle behavior and generate evacuation plans. In the NWADE mechanism, we introduce the neighborhood watch concept whereby each vehicle around the intersection will serve as a watcher to report or verify the abnormal behavior of any nearby vehicle and the intersection manager. We propose a blockchainbased verification framework to guarantee the integrity and trustworthiness of the individual travel plans optimized for the entire intersection. We have conducted extensive experimental studies on various traffic scenarios, and the experimental results demonstrate the practicality, effectiveness, and efficiency of our mechanism. 
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  8. Anonymous communication, that is secure end-to-end and unlinkable, plays a critical role in protecting user privacy by preventing service providers from using message metadata to discover communication links between any two users. Techniques, such as Mix-net, DC-net, time delay, cover traffic, Secure Multiparty Computation (SMC) and Private Information Retrieval, can be used to achieve anonymous communication. SMC-based approach generally offers stronger simulation based security guarantee. In this paper, we propose a simple and novel SMC approach to establishing anonymous communication, easily implementable with two non-colluding servers which have only communication and storage related capabilities. Our approach offers stronger security guarantee against malicious adversaries without incurring a great deal of extra computation. To show its practicality, we implemented our solutions using Chameleon Cloud to simulate the interactions among a million users, and extensive simulations were conducted to show message latency with various group sizes. Our approach is efficient for smaller group sizes and sub-group communication while preserving message integrity. Also, it does not have the message collision problem. 
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  9. Abstract Cross sections for the vibrational excitation and dissociative recombination (DR) of the C F 3 + ion in collisions with electrons at low scattering energies are computed using a previously-developed approach combining the normal mode approximation for the vibrational states of the target ion and the UK R -matrix code for the evaluation of the scattering matrices at fixed geometries. The obtained cross section for the DR shows excellent agreement with the experimental data from the ASTRID storage ring. Thermally-averaged rate coefficients are obtained from the cross sections for temperatures 10–3000 K. 
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