arXiv subjects

Zhibin Pu

Publications and source records attributed to Zhibin Pu.

3 recordsLinked to original sources

arXiv2026

HyCoSeq: Contextual Hyperbolic Representation Learning for Genomic Sequences

Hyperbolic geometry provides a natural inductive bias for genomic representation learning, but existing hyperbolic genomic models primarily use Lorentz convolutions to learn local sequence representations, while their residual pathways do not directly aggregate full Lorentz representations. We propose HyCoSeq, a contextual hyperbolic representation learning framework for genomic sequences. HyCoSeq incorporates weighted Lorentzian residual aggregation into multi-curvature Lorentz encoding, allowing full Lorentz representations to participate directly in geometry-consistent local aggregation. It further introduces a bidirectional long short-term memory network that integrates information from both sequence directions to learn contextual relationships among local representations at different positions within a genomic sequence, thereby extending local hyperbolic convolutional encoding to sequence-level contextualized representations. Extensive experiments across diverse genomic tasks show that HyCoSeq outperforms existing hyperbolic baselines and, without large-scale genomic pretraining, achieves competitive performance against substantially larger pretrained DNA language models.

cs.LG↗

arXiv2025

A near-exact linear mixed model for genome-wide association studies

Linear mixed models (LMM) are widely adopted in genome-wide association studies (GWAS) to account for population stratification and cryptic relatedness. However, the parameter estimation of LMMs imposes substantial computational burdens due to large-scale operations on genetic similarity matrices (GSM). We introduced the near-exact linear mixed model (NExt-LMM), a novel LMM framework that overcomes critical computational bottlenecks in GWAS through the following key innovations. Firstly, we exploit the inherent low-rank structure of the GSM iteratively with the Hierarchical Off-Diagonal Low-Rank (HODLR) format, which is much faster than traditional decomposition methods. Secondly, we leverage the HODLR-approximated GSM to dramatically accelerate the further maximum likelihood estimation with the shared heritability ratios. Moreover, we establish rigorous error bounds for the NExt-LMM estimator, proving that Kullback-Leibler divergence between the approximated and exact estimators can be arbitrarily small. Consequently, our proposed dual approach accelerates inference of LMMs while guaranteeing low approximation errors. We use numerical experiments to demonstrate that the NExt-LMM significantly improves inference efficiency compared to existing methods. We develop a Python package that is available at https://github.com/ZhibinPU/NExt-LMM.

stat.CO↗

arXiv2025

A spatial-correlated multitask linear mixed-effects model for imaging genetics

Imaging genetics aims to uncover the hidden relationship between imaging quantitative traits (QTs) and genetic markers (e.g. single nucleotide polymorphism (SNP)), and brings valuable insights into the pathogenesis of complex diseases, such as cancers and cognitive disorders (e.g. the Alzheimer's Disease). However, most linear models in imaging genetics didn't explicitly model the inner relationship among QTs, which might miss some potential efficiency gains from information borrowing across brain regions. In this work, we developed a novel Bayesian regression framework for identifying significant associations between QTs and genetic markers while explicitly modeling spatial dependency between QTs, with the main contributions as follows. Firstly, we developed a spatial-correlated multitask linear mixed-effects model (LMM) to account for dependencies between QTs. We incorporated a population-level mixed effects term into the model, taking full advantage of the dependent structure of brain imaging-derived QTs. Secondly, we implemented the model in the Bayesian framework and derived a Markov chain Monte Carlo (MCMC) algorithm to achieve the model inference. Further, we incorporated the MCMC samples with the Cauchy combination test (CCT) to examine the association between SNPs and QTs, which avoided computationally intractable multi-test issues. The simulation studies indicated improved power of our proposed model compared to classic models where inner dependencies of QTs were not modeled. We also applied the new spatial model to an imaging dataset obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database.

stat.ME↗