Sex-biased gene expression differs across human populations; however, the underlying genetic basis and molecular mechanisms remain largely unknown. Here, we explore the influence of ancestry on sex differences in the human transcriptome and its genetic effects on a Eurasian admixed population: Uyghurs living in Xinjiang (XJU), by analyzing whole-genome sequencing data and transcriptome data of 90 XJU and 40 unrelated Han Chinese individuals. We identified 302 sex-biased expressed genes and 174 sex-biased cis-expression quantitative loci (sb-cis-eQTLs) in XJU, which were enriched in innate immune-related functions, indicating sex differences in immunity. Notably, approximately one-quarter of the sb-cis-eQTLs showed a strong correlation with ancestry composition; i.e. populations of similar ancestry tended to show similar patterns of sex-biased gene expression. Our analysis further suggested that genetic admixture induced a moderate degree of sex-biased gene expression. Interestingly, analysis of chromosome interactions revealed that the X chromosome acted on autosomal immunity-associated genes, partially explaining the sex-biased phenotypic differences. Our work extends the knowledge of sex-biased gene expression from the perspective of genetic admixture and bridges the gap in the exploration of sex-biased phenotypes shaped by autosome and X-chromosome interactions. Notably, we demonstrated that sex chromosomes cannot fully explain sex differentiation in immune-related phenotypes.

Various methods have been proposed to reconstruct admixture histories by analyzing the length of ancestral chromosomal tracts, such as estimating the admixture time and number of admixture events. However, available methods do not explicitly consider the complex admixture structure, which characterizes the joining and mixing patterns of different ancestral populations during the admixture process, and instead assume a simplified one-by-one sequential admixture model. In this study, we proposed a novel approach that considers the non-sequential admixture structure to reconstruct admixture histories. Specifically, we introduced a hierarchical admixture model that incorporated four ancestral populations and developed a new method, called HierarchyMix, which uses the length of ancestral tracts and the number of ancestry switches along genomes to reconstruct the four-way admixture history. By automatically selecting the optimal admixture model using the Bayesian information criterion principles, HierarchyMix effectively estimates the corresponding admixture parameters. Simulation studies confirmed the effectiveness and robustness of HierarchyMix. We also applied HierarchyMix to Uyghurs and Kazakhs, enabling us to reconstruct the admixture histories of Central Asians. Our results highlight the importance of considering complex admixture structures and demonstrate that HierarchyMix is a useful tool for analyzing complex admixture events.

The smart grid (SG) is a new type of grid that integrates traditional power grid with the Internet of Things (IoT) to make the entire grid system more compatible, controllable and self-healing. However, the flourishing of SG still faces some challenges in term of privacy-preserving data aggregation. Previous multi-dimensional data aggregation schemes need heavy computation operations, cannot support multi-subset data aggregation, and resist neither collusion attack among the gateway (GW) and control center (CC) nor differential attack. To solve these issues, we propose a privacy-preserving data aggregation scheme for fog-based smart grids to achieve multi-dimensional and multi-subset data aggregation. The parallel composability of differential privacy is used to reasonably allocate the privacy budget, which can provide higher data utility in multi-dimensional data aggregation. In addition, each user’s multi-dimensional power consumption data will be structured as a composite data by utilizing Chinese Remainder Theorem (CRT), which will further reduce the computational overhead. Security analysis shows that our scheme can resist differential attack, eavesdropping attack, collusion attack and active attack. Evaluation of the performance also demonstrates that our scheme is more efficient in terms of computational overhead and communication overhead.

Sex-biased gene flow has been common in the demographic history of modern humans. However, the lack of sophisticated methods for delineating the detailed sex-biased admixture process prevents insights into complex admixture history and thus our understanding of the evolutionary mechanisms of genetic diversity. Here, we present a novel algorithm, MultiWaverX, for modeling complex admixture history with sex-biased gene flow. Systematic simulations showed that MultiWaverX is a powerful tool for modeling complex admixture history and inferring sex-biased gene flow. Application of MultiWaverX to empirical data of 17 typical admixed populations in America, Central Asia, and the Middle East revealed sex-biased admixture histories that were largely consistent with the historical records. Notably, fine-scale admixture process reconstruction enabled us to recognize latent sex-biased gene flow in certain populations that would likely be overlooked by much of the routine analysis with commonly used methods. An outstanding example in the real world is the Kazakh population that experienced complex admixture with sex-biased gene flow but in which the overall signature has been canceled due to biased gene flow from an opposite direction.

BACKGROUND: Y-chromosome DNA (Y-DNA) has been used for tracing paternal lineages and offers a clear path from an individual to a known, or likely, direct paternal ancestor. The advance of next-generation sequencing (NGS) technologies increasingly improves the resolution of the non-recombining region of the Y-chromosome (NRY). However, a lack of suitable computer tools prevents the use of NGS data from the Y-DNA studies. RESULTS: We developed Y-LineageTracker, a high-throughput analysis framework that not only utilizes state-of-the-art methodologies to automatically determine NRY haplogroups and identify microsatellite variants of Y-chromosome on a fine scale, but also optimizes comprehensive Y-DNA analysis methods for NGS data. Notably, Y-LineageTracker integrates the NRY haplogroup and Y-STR analysis modules with recognized strategies to robustly suggest an interpretation for paternal genetics and evolution. NRY haplogroup module mainly covers haplogroup classification, clustering analysis, phylogeny construction, and divergence time estimation of NRY haplogroups, and Y-STR module mainly includes Y-STR genotyping, statistical calculation, network analysis, and estimation of time to the most recent common ancestor (TMRCA) based on Y-STR haplotypes. Performance comparison indicated that Y-LineageTracker outperformed existing Y-DNA analysis tools for the high performance and satisfactory visualization effect. CONCLUSIONS: Y-LineageTracker is an open-source and user-friendly command-line tool that provide multiple functions to efficiently analyze Y-DNA from NGS data at both Y-SNP and Y-STR level. Additionally, Y-LineageTracker supports various formats of input data and produces high-quality figures suitable for publication. Y-LineageTracker is coded with Python3 and supports Windows, Linux, and macOS platforms, and can be installed manually or via the Python Package Index (PyPI). The source code, examples, and manual of Y-LineageTracker are freely available at https://www.picb.ac.cn/PGG/resource.php or CodeOcean ( https://codeocean.com/capsule/7424381/tree ).

BACKGROUND: Computer simulations have been widely applied in population genetics and evolutionary studies. A great deal of effort has been made over the past two decades in developing simulation tools. However, there are not many simulation tools suitable for studying population admixture. RESULTS: We here developed a forward-time simulator, AdmixSim 2, an individual-based tool that can flexibly and efficiently simulate population genomics data under complex evolutionary scenarios. Unlike its previous version, AdmixSim 2 is based on the extended Wright-Fisher model, and it implements many common evolutionary parameters to involve gene flow, natural selection, recombination, and mutation, which allow users to freely design and simulate any complex scenario involving population admixture. AdmixSim 2 can be used to simulate data of dioecious or monoecious populations, autosomes, or sex chromosomes. To our best knowledge, there are no similar tools available for the purpose of simulation of complex population admixture. Using empirical or previously simulated genomic data as input, AdmixSim 2 provides phased haplotype data for the convenience of further admixture-related analyses such as local ancestry inference, association studies, and other applications. We here evaluate the performance of AdmixSim 2 based on simulated data and validated functions via comparative analysis of simulated data and empirical data of African American, Mexican, and Uyghur populations. CONCLUSIONS: AdmixSim 2 is a flexible simulation tool expected to facilitate the study of complex population admixture in various situations.

The inference of demographic history of populations is an important undertaking in population genetics. A few recent studies have developed identity-by-descent (IBD) based methods to reveal the signature of the relatively recent historical events. Notably, Pe'er and his colleagues have introduced a novel method (named PIBD here) by employing IBD sharing to infer effective population size and migration rate. However, under island model, PIBD neglects the coalescent information before the time to the most recent common ancestor (tMRCA) which leads to apparent deviations in certain situations. In this paper, we propose a new method, MIBD, by adopting a Markov process to describe the island model and develop a new formula for estimating IBD sharing. The new formula considers the coalescent information before tMRCA and the joint effect of the coalescent and migration events. We apply both MIBD and PIBD to the genome-wide data of two human populations (Palestinian and Bedouin) obtained from the HGDP-CEPH database, and demonstrate that MIBD is competitive to PIBD. Our simulation analyses also show that the results of MIBD are more accurate than those of PIBD especially in the case of small effective population size.

BACKGROUND: Recombination plays an important role in the maintenance of genetic diversity in many types of organisms, especially diploid eukaryotes. Recombination can be studied and used to map diseases. However, recombination adds a great deal of complexity to the genetic information. This renders estimation of evolutionary parameters more difficult. After the coalescent process was formulated, models capable of describing recombination using graphs, such as ancestral recombination graphs (ARG) were also developed. There are two typical models based on which to simulate ARG: back-in-time model such as ms and spatial model including Wiuf&Hein's, SMC, SMC', and MaCS. RESULTS: In this study, a new method of modeling coalescence with recombination, Spatial Coalescent simulator (SC), was developed, which considerably improved the algorithm described by Wiuf and Hein. The present algorithm constructs ARG spatially along the sequence, but it does not produce any redundant branches which are inevitable in Wiuf and Hein's algorithm. Interestingly, the distribution of ARG generated by the present new algorithm is identical to that generated by a typical back-in-time model adopted by ms, an algorithm commonly used to model coalescence. It is here demonstrated that the existing approximate methods such as the sequentially Markov coalescent (SMC), a related method called SMC', and Markovian coalescent simulator (MaCS) can be viewed as special cases of the present method. Using simulation analysis, the time to the most common ancestor (TMRCA) in the local trees of ARGs generated by the present algorithm was found to be closer to that produced by ms than time produced by MaCS. Sample-consistent ARGs can be generated using the present method. This may significantly reduce the computational burden. CONCLUSION: In summary, the present method and algorithm may facilitate the estimation and description of recombination in population genomics and evolutionary biology.