SUMMARY: Admixed populations, with their unique and diverse genetic backgrounds, are often underrepresented in genetic studies. This oversight not only limits our understanding but also exacerbates existing health disparities. One major barrier has been the lack of efficient tools tailored for the special challenges of genetic studies of admixed populations. Here, we present admix-kit, an integrated toolkit and pipeline for genetic analyses of admixed populations. Admix-kit implements a suite of methods to facilitate genotype and phenotype simulation, association testing, genetic architecture inference, and polygenic scoring in admixed populations. AVAILABILITY AND IMPLEMENTATION: Admix-kit package is open-source and available at https://github.com/KangchengHou/admix-kit. Additionally, users can use the pipeline designed for admixed genotype simulation available at https://github.com/UW-GAC/admix-kit_workflow.

MOTIVATION: Existing methods for simulating synthetic genotype and phenotype datasets have limited scalability, constraining their usability for large-scale analyses. Moreover, a systematic approach for evaluating synthetic data quality and a benchmark synthetic dataset for developing and evaluating methods for polygenic risk scores are lacking. RESULTS: We present HAPNEST, a novel approach for efficiently generating diverse individual-level genotypic and phenotypic data. In comparison to alternative methods, HAPNEST shows faster computational speed and a lower degree of relatedness with reference panels, while generating datasets that preserve key statistical properties of real data. These desirable synthetic data properties enabled us to generate 6.8 million common variants and nine phenotypes with varying degrees of heritability and polygenicity across 1 million individuals. We demonstrate how HAPNEST can facilitate biobank-scale analyses through the comparison of seven methods to generate polygenic risk scoring across multiple ancestry groups and different genetic architectures. AVAILABILITY AND IMPLEMENTATION: A synthetic dataset of 1 008 000 individuals and nine traits for 6.8 million common variants is available at https://www.ebi.ac.uk/biostudies/studies/S-BSST936. The HAPNEST software for generating synthetic datasets is available as Docker/Singularity containers and open source Julia and C code at https://github.com/intervene-EU-H2020/synthetic_data.

Accurately ranking the vast number of candidate detections is crucial for dense object detectors to achieve high performance. Prior work uses the classification score or a combination of classification and predicted localization scores to rank candidates. However, neither option results in a reliable ranking, thus degrading detection performance. In this paper, we propose to learn an Iou-Aware Classification Score (IACS) as a joint representation of object presence confidence and localization accuracy. We show that dense object detectors can achieve a more accurate ranking of candidate detections based on the IACS. We design a new loss function, named Varifocal Loss, to train a dense object detector to predict the IACS, and propose a new star-shaped bounding box feature representation for IACS prediction and bounding box refinement. Combining these two new components and a bounding box refinement branch, we build an IoU-aware dense object detector based on the FCOS+ATSS architecture, that we call VarifocalNet or VFNet for short. Extensive experiments on MS COCO show that our VFNet consistently surpasses the strong baseline by ~2.0 AP with different backbones. Our best model VFNet-X-1200 with Res2Net-101-DCN achieves a single-model single-scale AP of 55.1 on COCO test-dev, which is state-of-the-art among various object detectors. Code is available at: https://github.com/hyz-xmaster/VarifocalNet.