Zhe Luo

Lei Huang, Hui Shen, Kuan-Jui Su et al.

Genotype-based cis-expression prediction depends on accurately modeling local regulatory architecture. We present block-sparse Bayesian sparse linear mixed model (bsBSLMM), an extension of Bayesian sparse linear mixed model (BSLMM) that incorporates linkage disequilibrium (LD)-block spike-and-slab sparsity and a transcription start site (TSS)-informed SNP inclusion prior. Across 23,098 genes from GEUVADIS European-ancestry lymphoblastoid cell lines, bsBSLMM retained more predictable genes than BSLMM, LASSO, BLUP, TIGAR elastic net, and TIGAR Dirichlet-process regression under matched evaluation criteria. Compared with BSLMM, bsBSLMM improved held-out prediction performance for most shared genes, with gains driven primarily by LD-block sparsity and further enhanced by the TSS-informed prior. Variants selected by bsBSLMM showed stronger enrichment in GM12878 DNase and H3K27ac regulatory regions than variants selected by BSLMM. In transcriptome-wide association study (TWAS) analysis, bsBSLMM recovered established inflammatory bowel disease signals, including IL23R, and identified additional genome-wide significant genes not detected by BSLMM. Independent validation in the Louisiana Osteoporosis Study reproduced the increased prediction yield across ancestries and recovered biologically relevant bone mineral density pathways in downstream TWAS and gene set enrichment analyses. These results demonstrate that incorporating LD-block structure and biologically informed SNP priors improves cis-expression prediction and enhances downstream TWAS discovery.

Chen Zhao, Joyce H Keyak, Xuewei Cao et al.

The aim of this paper is to design a deep learning-based model to predict proximal femoral strength using multi-view information fusion. Method: We developed new models using multi-view variational autoencoder (MVAE) for feature representation learning and a product of expert (PoE) model for multi-view information fusion. We applied the proposed models to an in-house Louisiana Osteoporosis Study (LOS) cohort with 931 male subjects, including 345 African Americans and 586 Caucasians. With an analytical solution of the product of Gaussian distribution, we adopted variational inference to train the designed MVAE-PoE model to perform common latent feature extraction. We performed genome-wide association studies (GWAS) to select 256 genetic variants with the lowest p-values for each proximal femoral strength and integrated whole genome sequence (WGS) features and DXA-derived imaging features to predict proximal femoral strength. Results: The best prediction model for fall fracture load was acquired by integrating WGS features and DXA-derived imaging features. The designed models achieved the mean absolute percentage error of 18.04%, 6.84% and 7.95% for predicting proximal femoral fracture loads using linear models of fall loading, nonlinear models of fall loading, and nonlinear models of stance loading, respectively. Compared to existing multi-view information fusion methods, the proposed MVAE-PoE achieved the best performance. Conclusion: The proposed models are capable of predicting proximal femoral strength using WGS features and DXA-derived imaging features. Though this tool is not a substitute for FEA using QCT images, it would make improved assessment of hip fracture risk more widely available while avoiding the increased radiation dosage and clinical costs from QCT.

Chen Zhao, Kuan-Jui Su, Chong Wu et al.

Background: Missing data is a common challenge in mass spectrometry-based metabolomics, which can lead to biased and incomplete analyses. The integration of whole-genome sequencing (WGS) data with metabolomics data has emerged as a promising approach to enhance the accuracy of data imputation in metabolomics studies. Method: In this study, we propose a novel method that leverages the information from WGS data and reference metabolites to impute unknown metabolites. Our approach utilizes a multi-view variational autoencoder to jointly model the burden score, polygenetic risk score (PGS), and linkage disequilibrium (LD) pruned single nucleotide polymorphisms (SNPs) for feature extraction and missing metabolomics data imputation. By learning the latent representations of both omics data, our method can effectively impute missing metabolomics values based on genomic information. Results: We evaluate the performance of our method on empirical metabolomics datasets with missing values and demonstrate its superiority compared to conventional imputation techniques. Using 35 template metabolites derived burden scores, PGS and LD-pruned SNPs, the proposed methods achieved R^2-scores > 0.01 for 71.55% of metabolites. Conclusion: The integration of WGS data in metabolomics imputation not only improves data completeness but also enhances downstream analyses, paving the way for more comprehensive and accurate investigations of metabolic pathways and disease associations. Our findings offer valuable insights into the potential benefits of utilizing WGS data for metabolomics data imputation and underscore the importance of leveraging multi-modal data integration in precision medicine research.

Chenhe Du, Xiyue Lin, Qing Wu et al.

Limited-angle and sparse-view computed tomography (LACT and SVCT) are crucial for expanding the scope of X-ray CT applications. However, they face challenges due to incomplete data acquisition, resulting in diverse artifacts in the reconstructed CT images. Emerging implicit neural representation (INR) techniques, such as NeRF, NeAT, and NeRP, have shown promise in under-determined CT imaging reconstruction tasks. However, the unsupervised nature of INR architecture imposes limited constraints on the solution space, particularly for the highly ill-posed reconstruction task posed by LACT and ultra-SVCT. In this study, we introduce the Diffusion Prior Driven Neural Representation (DPER), an advanced unsupervised framework designed to address the exceptionally ill-posed CT reconstruction inverse problems. DPER adopts the Half Quadratic Splitting (HQS) algorithm to decompose the inverse problem into data fidelity and distribution prior sub-problems. The two sub-problems are respectively addressed by INR reconstruction scheme and pre-trained score-based diffusion model. This combination first injects the implicit image local consistency prior from INR. Additionally, it effectively augments the feasibility of the solution space for the inverse problem through the generative diffusion model, resulting in increased stability and precision in the solutions. We conduct comprehensive experiments to evaluate the performance of DPER on LACT and ultra-SVCT reconstruction with two public datasets (AAPM and LIDC), an in-house clinical COVID-19 dataset and a public raw projection dataset created by Mayo Clinic. The results show that our method outperforms the state-of-the-art reconstruction methods on in-domain datasets, while achieving significant performance improvements on out-of-domain (OOD) datasets.

Lei Huang, Chuan Qiu, Kuan-Jui Su et al.

Genotype imputation enables dense variant coverage for genome-wide association and risk-prediction studies, yet conventional reference-panel methods remain limited by ancestry bias and reduced rare-variant accuracy. We present Genotype Bidirectional Encoder Representations from Transformers (GenoBERT), a transformer-based, reference-free framework that tokenizes phased genotypes and uses a self-attention mechanism to capture both short- and long-range linkage disequilibrium (LD) dependencies. Benchmarking on two independent datasets including the Louisiana Osteoporosis Study (LOS) and the 1000 Genomes Project (1KGP) across ancestry groups and multiple genotype missingness levels (5-50%) shows that GenoBERT achieves the highest overall accuracy compared to four baseline methods (Beagle5.4, SCDA, BiU-Net, and STICI). At practical sparsity levels (up to 25% missing), GenoBERT attains high overall imputation accuracy ($r^2 approx 0.98$) across datasets, and maintains robust performance ($r^2 > 0.90$) even at 50% missingness. Experimental results across different ancestries confirm consistent gains across datasets, with resilience to small sample sizes and weak LD. A 128-SNP (single-nucleotide polymorphism) context window (approximately 100 Kb) is validated through LD-decay analyses as sufficient to capture local correlation structures. By eliminating reference-panel dependence while preserving high accuracy, GenoBERT provides a scalable and robust solution for genotype imputation and a foundation for downstream genomic modeling.

Zhe Luo, Wenjing Jia, Stuart Perry

Three-dimensional (3D) point clouds are becoming increasingly vital in applications such as autonomous driving, augmented reality, and immersive communication, demanding real-time processing and low latency. However, their large data volumes and bandwidth constraints hinder the deployment of high-quality services in resource-limited environments. Progres- sive coding, which allows for decoding at varying levels of detail, provides an alternative by allowing initial partial decoding with subsequent refinement. Although recent learning-based point cloud geometry coding methods have achieved notable success, their fixed latent representation does not support progressive decoding. To bridge this gap, we propose ProDAT, a novel density-aware tail-drop mechanism for progressive point cloud coding. By leveraging density information as a guidance signal, latent features and coordinates are decoded adaptively based on their significance, therefore achieving progressive decoding at multiple bitrates using one single model. Experimental results on benchmark datasets show that the proposed ProDAT not only enables progressive coding but also achieves superior coding efficiency compared to state-of-the-art learning-based coding techniques, with over 28.6% BD-rate improvement for PSNR- D2 on SemanticKITTI and over 18.15% for ShapeNet

Zhi Xiao, Zhe Luo, Bo Zhong et al.

Well-known for its simplicity and effectiveness in classification, AdaBoost, however, suffers from overfitting when class-conditional distributions have significant overlap. Moreover, it is very sensitive to noise that appears in the labels. This article tackles the above limitations simultaneously via optimizing a modified loss function (i.e., the conditional risk). The proposed approach has the following two advantages. (1) It is able to directly take into account label uncertainty with an associated label confidence. (2) It introduces a "trustworthiness" measure on training samples via the Bayesian risk rule, and hence the resulting classifier tends to have finite sample performance that is superior to that of the original AdaBoost when there is a large overlap between class conditional distributions. Theoretical properties of the proposed method are investigated. Extensive experimental results using synthetic data and real-world data sets from UCI machine learning repository are provided. The empirical study shows the high competitiveness of the proposed method in predication accuracy and robustness when compared with the original AdaBoost and several existing robust AdaBoost algorithms.