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Abstract Background Estimation of genetic relatedness, or kinship, is used occasionally for recreational purposes and in forensic applications. While numerous methods were developed to estimate kinship, they suffer from high computational requirements and often make an untenable assumption of homogeneous population ancestry of the samples. Moreover, genetic privacy is generally overlooked in the usage of kinship estimation methods. There can be ethical concerns about finding unknown familial relationships in third-party databases. Similar ethical concerns may arise while estimating and reporting sensitive population-level statistics such as inbreeding coefficients for the concerns around marginalization and stigmatization.
Results Here, we present SIGFRIED, which makes use of existing reference panels with a projection-based approach that simplifies kinship estimation in the admixed populations. We use simulated and real datasets to demonstrate the accuracy and efficiency of kinship estimation. We present a secure federated kinship estimation framework and implement a secure kinship estimator using homomorphic encryption-based primitives for computing relatedness between samples in two different sites while genotype data are kept confidential. Source code and documentation for our methods can be found at https://doi.org/10.5281/zenodo.7053352.
Conclusions Analysis of relatedness is fundamentally important for identifying relatives, in association studies, and for estimation of population-level estimates of inbreeding. As the awareness of individual and group genomic privacy is growing, privacy-preserving methods for the estimation of relatedness are needed. Presented methods alleviate the ethical and privacy concerns in the analysis of relatedness in admixed, historically isolated and underrepresented populations.
Short Abstract Genetic relatedness is a central quantity used for finding relatives in databases, correcting biases in genome wide association studies and for estimating population-level statistics. Methods for estimating genetic relatedness have high computational requirements, and occasionally do not consider individuals from admixed ancestries. Furthermore, the ethical concerns around using genetic data and calculating relatedness are not considered. We present a projection-based approach that can efficiently and accurately estimate kinship. We implement our method using encryption-based techniques that provide provable security guarantees to protect genetic data while kinship statistics are computed among multiple sites.
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In polynuclear biological active sites, multiple electrons are needed for turnover, and the distribution of these electrons among the metal sites is affected by the structure of the active site. However, the study of the interplay between structure and redox distribution is difficult not only in biological systems but also in synthetic polynuclear clusters since most redox changes produce only one thermodynamically stable product. Here, the unusual chemistry of a sterically hindered trichromium complex allowed us to probe the relationship between structural and redox isomerism. Two structurally isomeric trichromium imides were isolated: asymmetric terminal imide ( tbs L)Cr 3 (NDipp) and symmetric, μ 3 -bridging imide ( tbs L)Cr 3 (μ 3 –NBn) (( tbs L) 6− = (1,3,5-C 6 H 9 (NC 6 H 4 - o -NSi t BuMe 2 ) 3 ) 6− ). Along with the homovalent isocyanide adduct ( tbs L)Cr 3 (CNBn) and the bisimide ( tbs L)Cr 3 (μ 3 –NPh)(NPh), both imide isomers were examined by multiple-wavelength anomalous diffraction (MAD) to determine the redox load distribution by the free refinement of atomic scattering factors. Despite their compositional similarities, the bridging imide shows uniform oxidation of all three Cr sites while the terminal imide shows oxidation at only two Cr sites. Further oxidation from the bridging imide to the bisimide is only borne at the Cr site bound to the second, terminal imido fragment. Thus, depending on the structural motifs present in each [Cr 3 ] complex, MAD revealed complete localization of oxidation, partial localization, and complete delocalization, all supported by the same hexadentate ligand scaffold.more » « less
