arXiv subjects

Kuan-Jui Su

Publications and source records attributed to Kuan-Jui Su.

12 recordsLinked to original sources

arXiv2026

Annotation-Informed Block-Sparse Bayesian Modeling for cis-Expression Prediction

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.

q-bio.GN↗

arXiv2026

DXA-Derived Skeletal Phenotypes and Hip Fracture Risk: A Backdoor-Adjusted Causal Analysis

Purpose: To compare dual-energy X-ray absorptiometry (DXA)-derived hip skeletal phenotypes in relation to hip fracture risk using prespecified confounder adjustment and to assess whether phenotypes ranked by their backdoor-adjusted average treatment effects (ATEs) improve risk stratification. Methods: We analyzed 21,098 UK Biobank participants with linked health records, hip DXA-derived skeletal measures, and prespecified covariates. Sixteen phenotypes spanning bone mineral content (BMC), bone mineral density (BMD), and T-score across hip-related regions were evaluated. Confounder selection was guided by a prespecified directed acyclic graph (DAG). Backdoor-adjusted ATEs were estimated on the absolute risk-difference scale per standard deviation (SD) increase. Effect heterogeneity was evaluated for total femur BMD, and downstream prediction was assessed using clinical variables combined with phenotypes ranked by ATE magnitude. Results: Among 21,098 participants, 115 had hip fractures. All 16 phenotypes showed negative backdoor-adjusted ATEs per SD increase. The largest ATEs were observed for total femur BMC and total femur BMD, each with a risk difference of -0.0047, corresponding to approximately 4.7 fewer hip fractures per 1,000 participants per SD higher phenotype value. Conditional effects of total femur BMD were stronger among older participants and those with lower BMI. In prediction, clinical variables plus the top 11 ATE-ranked phenotypes achieved higher AUC than FRAX with femoral neck BMD (0.842 vs. 0.709), with higher sensitivity (0.748 vs. 0.443) and similar specificity (0.793 vs. 0.777). Conclusion: DXA-derived hip skeletal phenotypes differed in their backdoor-adjusted ATEs. Phenotype-level causal evaluation may help identify informative DXA measures for risk stratification.

q-bio.QM↗

arXiv2026

GenoBERT: A Language Model for Accurate Genotype Imputation

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.

q-bio.GN↗

arXiv2026

Improving Generalizability of Hip Fracture Risk Prediction via Domain Adaptation Across Multiple Cohorts

Clinical risk prediction models often fail to be generalized across cohorts because underlying data distributions differ by clinical site, region, demographics, and measurement protocols. This limitation is particularly pronounced in hip fracture risk prediction, where the performance of models trained on one cohort (the source cohort) can degrade substantially when deployed in other cohorts (target cohorts). We used a shared set of clinical and DXA-derived features across three large cohorts - the Study of Osteoporotic Fractures (SOF), the Osteoporotic Fractures in Men Study (MrOS), and the UK Biobank (UKB), to systematically evaluate the performance of three domain adaptation methods - Maximum Mean Discrepancy (MMD), Correlation Alignment (CORAL), and Domain - Adversarial Neural Networks (DANN) and their combinations. For a source cohort with males only and a source cohort with females only, domain-adaptation methods consistently showed improved performance than the no-adaptation baseline (source-only training), and the use of combinations of multiple domain adaptation methods delivered the largest and most stable gains. The method that combines MMD, CORAL, and DANN achieved the highest discrimination with the area under curve (AUC) of 0.88 for a source cohort with males only and 0.95 for a source cohort with females only), demonstrating that integrating multiple domain adaptation methods could produce feature representations that are less sensitive to dataset differences. Unlike existing methods that rely heavily on supervised tuning or assume known outcomes of samples in target cohorts, our outcome-free approaches enable the model selection under realistic deployment conditions and improve generalization of models in hip fracture risk prediction.

cs.LG↗

arXiv2025

PF-DAformer: Proximal Femur Segmentation via Domain Adaptive Transformer for Dual-Center QCT

Quantitative computed tomography (QCT) plays a crucial role in assessing bone strength and fracture risk by enabling volumetric analysis of bone density distribution in the proximal femur. However, deploying automated segmentation models in practice remains difficult because deep networks trained on one dataset often fail when applied to another. This failure stems from domain shift, where scanners, reconstruction settings, and patient demographics vary across institutions, leading to unstable predictions and unreliable quantitative metrics. Overcoming this barrier is essential for multi-center osteoporosis research and for ensuring that radiomics and structural finite element analysis results remain reproducible across sites. In this work, we developed a domain-adaptive transformer segmentation framework tailored for multi-institutional QCT. Our model is trained and validated on one of the largest hip fracture related research cohorts to date, comprising 1,024 QCT images scans from Tulane University and 384 scans from Rochester, Minnesota for proximal femur segmentation. To address domain shift, we integrate two complementary strategies within a 3D TransUNet backbone: adversarial alignment via Gradient Reversal Layer (GRL), which discourages the network from encoding site-specific cues, and statistical alignment via Maximum Mean Discrepancy (MMD), which explicitly reduces distributional mismatches between institutions. This dual mechanism balances invariance and fine-grained alignment, enabling scanner-agnostic feature learning while preserving anatomical detail.

cs.CV↗

arXiv2025

An Advanced Two-Stage Model with High Sensitivity and Generalizability for Prediction of Hip Fracture Risk Using Multiple Datasets

Hip fractures are a major cause of disability, mortality, and healthcare burden in older adults, underscoring the need for early risk assessment. However, commonly used tools such as the DXA T-score and FRAX often lack sensitivity and miss individuals at high risk, particularly those without prior fractures or with osteopenia. To address this limitation, we propose a sequential two-stage model that integrates clinical and imaging information to improve prediction accuracy. Using data from the Osteoporotic Fractures in Men Study (MrOS), the Study of Osteoporotic Fractures (SOF), and the UK Biobank, Stage 1 (Screening) employs clinical, demographic, and functional variables to estimate baseline risk, while Stage 2 (Imaging) incorporates DXA-derived features for refinement. The model was rigorously validated through internal and external testing, showing consistent performance and adaptability across cohorts. Compared to T-score and FRAX, the two-stage framework achieved higher sensitivity and reduced missed cases, offering a cost-effective and personalized approach for early hip fracture risk assessment. Keywords: Hip Fracture, Two-Stage Model, Risk Prediction, Sensitivity, DXA, FRAX

cs.LG↗

arXiv2025

ICGM-FRAX: Iterative Cross Graph Matching for Hip Fracture Risk Assessment using Dual-energy X-ray Absorptiometry Images

Hip fractures represent a major health concern, particularly among the elderly, often leading decreased mobility and increased mortality. Early and accurate detection of at risk individuals is crucial for effective intervention. In this study, we propose Iterative Cross Graph Matching for Hip Fracture Risk Assessment (ICGM-FRAX), a novel approach for predicting hip fractures using Dual-energy X-ray Absorptiometry (DXA) images. ICGM-FRAX involves iteratively comparing a test (subject) graph with multiple template graphs representing the characteristics of hip fracture subjects to assess the similarity and accurately to predict hip fracture risk. These graphs are obtained as follows. The DXA images are separated into multiple regions of interest (RoIs), such as the femoral head, shaft, and lesser trochanter. Radiomic features are then calculated for each RoI, with the central coordinates used as nodes in a graph. The connectivity between nodes is established according to the Euclidean distance between these coordinates. This process transforms each DXA image into a graph, where each node represents a RoI, and edges derived by the centroids of RoIs capture the spatial relationships between them. If the test graph closely matches a set of template graphs representing subjects with incident hip fractures, it is classified as indicating high hip fracture risk. We evaluated our method using 547 subjects from the UK Biobank dataset, and experimental results show that ICGM-FRAX achieved a sensitivity of 0.9869, demonstrating high accuracy in predicting hip fractures.

cs.CV↗

arXiv2025

A Privacy-Preserving Domain Adversarial Federated learning for multi-site brain functional connectivity analysis

Resting-state functional magnetic resonance imaging (rs-fMRI) and its derived functional connectivity networks (FCNs) have become critical for understanding neurological disorders. However, collaborative analyses and the generalizability of models still face significant challenges due to privacy regulations and the non-IID (non-independent and identically distributed) property of multiple data sources. To mitigate these difficulties, we propose Domain Adversarial Federated Learning (DAFed), a novel federated deep learning framework specifically designed for non-IID fMRI data analysis in multi-site settings. DAFed addresses these challenges through feature disentanglement, decomposing the latent feature space into domain-invariant and domain-specific components, to ensure robust global learning while preserving local data specificity. Furthermore, adversarial training facilitates effective knowledge transfer between labeled and unlabeled datasets, while a contrastive learning module enhances the global representation of domain-invariant features. We evaluated DAFed on the diagnosis of ASD and further validated its generalizability in the classification of AD, demonstrating its superior classification accuracy compared to state-of-the-art methods. Additionally, an enhanced Score-CAM module identifies key brain regions and functional connectivity significantly associated with ASD and MCI, respectively, uncovering shared neurobiological patterns across sites. These findings highlight the potential of DAFed to advance multi-site collaborative research in neuroimaging while protecting data confidentiality.

cs.LG↗

arXiv2024

A Staged Approach using Machine Learning and Uncertainty Quantification to Predict the Risk of Hip Fracture

Despite advancements in medical care, hip fractures impose a significant burden on individuals and healthcare systems. This paper focuses on the prediction of hip fracture risk in older and middle-aged adults, where falls and compromised bone quality are predominant factors. We propose a novel staged model that combines advanced imaging and clinical data to improve predictive performance. By using CNNs to extract features from hip DXA images, along with clinical variables, shape measurements, and texture features, our method provides a comprehensive framework for assessing fracture risk. A staged machine learning-based model was developed using two ensemble models: Ensemble 1 (clinical variables only) and Ensemble 2 (clinical variables and DXA imaging features). This staged approach used uncertainty quantification from Ensemble 1 to decide if DXA features are necessary for further prediction. Ensemble 2 exhibited the highest performance, achieving an AUC of 0.9541, an accuracy of 0.9195, a sensitivity of 0.8078, and a specificity of 0.9427. The staged model also performed well, with an AUC of 0.8486, an accuracy of 0.8611, a sensitivity of 0.5578, and a specificity of 0.9249, outperforming Ensemble 1, which had an AUC of 0.5549, an accuracy of 0.7239, a sensitivity of 0.1956, and a specificity of 0.8343. Furthermore, the staged model suggested that 54.49% of patients did not require DXA scanning. It effectively balanced accuracy and specificity, offering a robust solution when DXA data acquisition is not always feasible. Statistical tests confirmed significant differences between the models, highlighting the advantages of the advanced modeling strategies. Our staged approach could identify individuals at risk with a high accuracy but reduce the unnecessary DXA scanning. It has great promise to guide interventions to prevent hip fractures with reduced cost and radiation.

physics.med-ph↗

arXiv2024

Multi-View Variational Autoencoder for Missing Value Imputation in Untargeted Metabolomics

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.

q-bio.GN↗

arXiv2023

Somatomotor-Visual Resting State Functional Connectivity Increases After Two Years in the UK Biobank Longitudinal Cohort

Purpose: Functional magnetic resonance imaging (fMRI) and functional connectivity (FC) have been used to follow aging in both children and older adults. Robust changes have been observed in children, where high connectivity among all brain regions changes to a more modular structure with maturation. In this work, we examine changes in FC in older adults after two years of aging in the UK Biobank longitudinal cohort. Approach: We process data using the Power264 atlas, then test whether FC changes in the 2,722-subject longitudinal cohort are statistically significant using a Bonferroni-corrected t-test. We also compare the ability of Power264 and UKB-provided, ICA-based FC to determine which of a longitudinal scan pair is older. Results: We find a 6.8\% average increase in SMT-VIS connectivity from younger to older scan (from $ρ=0.39$ to $ρ=0.42$) that occurs in male, female, older subject ($>65$ years old), and younger subject ($<55$ years old) groups. Among all inter-network connections, this average SMT-VIS connectivity is the best predictor of relative scan age, accurately predicting which scan is older 57\% of the time. Using the full FC and a training set of 2,000 subjects, one is able to predict which scan is older 82.5\% of the time using either the full Power264 FC or the UKB-provided ICA-based FC. Conclusions: We conclude that SMT-VIS connectivity increases in the longitudinal cohort, while resting state FC increases generally with age in the cross-sectional cohort. However, we consider the possibility of a change in resting state scanner task between UKB longitudinal data acquisitions.

q-bio.NC↗

arXiv2023

Identifiability in Functional Connectivity May Unintentionally Inflate Prediction Results

Functional magnetic resonance (fMRI) is an invaluable tool in studying cognitive processes in vivo. Many recent studies use functional connectivity (FC), partial correlation connectivity (PC), or fMRI-derived brain networks to predict phenotypes with results that sometimes cannot be replicated. At the same time, FC can be used to identify the same subject from different scans with great accuracy. In this paper, we show a method by which one can unknowingly inflate classification results from 61% accuracy to 86% accuracy by treating longitudinal or contemporaneous scans of the same subject as independent data points. Using the UK Biobank dataset, we find one can achieve the same level of variance explained with 50 training subjects by exploiting identifiability as with 10,000 training subjects without double-dipping. We replicate this effect in four different datasets: the UK Biobank (UKB), the Philadelphia Neurodevelopmental Cohort (PNC), the Bipolar and Schizophrenia Network for Intermediate Phenotypes (BSNIP), and an OpenNeuro Fibromyalgia dataset (Fibro). The unintentional improvement ranges between 7% and 25% in the four datasets. Additionally, we find that by using dynamic functional connectivity (dFC), one can apply this method even when one is limited to a single scan per subject. One major problem is that features such as ROIs or connectivities that are reported alongside inflated results may confuse future work. This article hopes to shed light on how even minor pipeline anomalies may lead to unexpectedly superb results.

q-bio.NC↗