In post-genome-wide association study era, interpretation of noncoding variants remains a significant challenge due to their complexity and the limited understanding of their functions. Here, we developed MIRACN, a novel residual convolutional neural network designed to predict cell line-specific functional regulatory variants. By utilizing a substantial dataset from massively parallel reporter assays (MPRAs) and employing a multitask learning strategy, MIRACN was trained across seven distinct cell lines, attaining superior performance compared to existing methods, especially in predicting cell type specificity. Comparative evaluations on an independent MPRA test dataset demonstrated that MIRACN not only outperformed in identifying regulatory variants but also provided valuable insights into their cellular context-specific regulatory mechanisms. MIRACN is capable of not only providing scores for functional variants but also pinpointing the specific cell line in which these variants display their function. This enhancement has improved the resolution of current research on the functionality of noncoding variants and has paved the way for more precise diagnostic and therapeutic strategies.

Accurately inferring clonal mutational profiles is essential for understanding intra-tumor heterogeneity and clonal selection during tumor evolution. Single-cell multi-modal genomic data, such as copy numbers and point mutations, can be integrated to deliver multiple views of the clonal mutational patterns. Despite of the fact that integration of single-cell multi-modal data has been extensively explored in existing studies, computational methods specifically developed to integrate copy number and point mutation data of single cells are still highly needed. We introduce a deep joint representation learning framework called scCMP, to accurately identify clonal mutational profiles. scCMP employs hybrid Transformer-CNN architectures and graph convolutional networks to integrate single-cell copy number and point mutation data. By fusing individual and commonality information among the two modalities, it generates meaningful cell embeddings for identifying clonal clusters. We comprehensively evaluate the effectiveness of scCMP on five real single-cell DNA sequencing datasets, and further showcase its good scalability on datasets generated from other omics technologies. The results show scCMP accurately aggregates the cells with similar mutational profiles into a same cluster, and surpasses the state-of-the-art methods, indicating its advantage in integrating single-cell genomic data.

Dropout events and technical noise are pervasive challenges in single-cell RNA sequencing (scRNA-seq) data, often obscuring true gene expression profiles and undermining the reliability of downstream analyses. Existing imputation and denoising methods offer partial relief but frequently struggle with over-smoothing and fail to fully capture the complex heterogeneity of cellular states. To address these limitations, we introduce scSTD, a novel imputation and denoising framework that uniquely combines the Swin Transformer (SwinT) architecture with a latent diffusion model. In scSTD, a deep autoencoder first encodes each cell into a compact latent embedding, which is then modeled via a SwinT-based latent diffusion process designed to learn the rich, multimodal distribution of scRNA-seq data. This integration enables scSTD to accurately recover gene expression profiles while preserving subtle biological variation. By synthesizing realistic latent neighbors for each cell and aggregating their decoded outputs, scSTD achieves high-fidelity imputation and denoising. Comprehensive evaluations on both synthetic and real scRNA-seq datasets demonstrate that scSTD significantly outperforms existing methods in recovering true gene expression profiles and maintaining the topological integrity of cellular landscapes.

Single-cell DNA sequencing (scDNA-seq) has been an effective means to unscramble intra-tumor heterogeneity, while joint inference of tumor clones and their respective copy number profiles remains a challenging task due to the noisy nature of scDNA-seq data. We introduce a new bioinformatics method called CoT for deciphering clonal copy number substructure. The backbone of CoT is a Copy number Transformer autoencoder that leverages multi-head attention mechanism to explore correlations between different genomic regions, and thus capture global features to create latent embeddings for the cells. CoT makes it convenient to first infer cell subpopulations based on the learned embeddings, and then estimate single-cell copy numbers through joint analysis of read counts data for the cells belonging to the same cluster. This exploitation of clonal substructure information in copy number analysis helps to alleviate the effect of read counts non-uniformity, and yield robust estimations of the tumor copy numbers. Performance evaluation on synthetic and real datasets showcases that CoT outperforms the state of the arts, and is highly useful for deciphering clonal copy number substructure.

Intra-tumor heterogeneity (ITH) is one of the major confounding factors that result in cancer relapse, and deciphering ITH is essential for personalized therapy. Single-cell DNA sequencing (scDNA-seq) now enables profiling of single-cell copy number alterations (CNAs) and thus aids in high-resolution inference of ITH. Here, we introduce an integrated framework called rcCAE to accurately infer cell subpopulations and single-cell CNAs from scDNA-seq data. A convolutional autoencoder (CAE) is employed in rcCAE to learn latent representation of the cells as well as distill copy number information from noisy read counts data. This unsupervised representation learning via the CAE model makes it convenient to accurately cluster cells over the low-dimensional latent space, and detect single-cell CNAs from enhanced read counts data. Extensive performance evaluations on simulated datasets show that rcCAE outperforms the existing CNA calling methods, and is highly effective in inferring clonal architecture. Furthermore, evaluations of rcCAE on two real datasets demonstrate that it is able to provide a more refined clonal structure, of which some details are lost in clonal inference based on integer copy numbers.

Differences in the motion of different parts of a target cause the echo signal to contain specific Doppler modulation information, i.e., the micro-Doppler (m-D) effect. This phenomenon provides an effective way to detect targets in marine environments. In this study, based on the establishment of the micromotion model of a rotating surveillance radar and analysis of the m-D frequency, the geometrical optics and physical optics (GO-PO) method and the time-frequency analysis technique are used to obtain the radar cross section (RCS) and m-D signature of a ship with a shipborne radar at different observation angles. The ship, as the main component of the echo, is associated with the main energy. Finding the optimum angle to observe the shipborne radar is of great importance. The results show that the m-D signatures of the shipborne radar are not clear when the elevation angle is greater than 60° but are clear when the elevation angle is less than 55°. Moreover, some motion parameters can be extracted from the m-D signature, such as the period of the ship micromotion. The rotation speed of the shipborne radar can be obtained and is consistent with the set speed. This can help identify and track the key parts of a ship with local motion.