arXiv subjects

Alisa Yurovsky

Publications and source records attributed to Alisa Yurovsky.

5 recordsLinked to original sources

arXiv2026

RankByGene: Gene-Guided Histopathology Representation Learning Through Cross-Modal Ranking Consistency

Spatial transcriptomics (ST) provides essential spatial context by mapping gene expression within tissue, enabling detailed study of cellular heterogeneity and tissue organization. However, aligning ST data with histology images poses challenges due to inherent spatial distortions and modality-specific variations. Existing methods largely rely on direct alignment, which often fails to capture complex cross-modal relationships. To address these limitations, we propose a novel framework that aligns gene and image features using a ranking-based alignment loss, preserving relative similarity across modalities and enabling robust multi-scale alignment. To further enhance the alignment's stability, we employ self-supervised knowledge distillation with a teacher-student network architecture, which serves as an intra-modal stability regularizer that prevents image-representation drift during cross-modal alignment. Extensive experiments on seven public datasets that encompass gene expression prediction, slide-level classification, and survival analysis demonstrate the efficacy of our method, showing improved alignment and predictive performance over existing methods. Code is available at https://github.com/winston52/RankByGene.

eess.IV↗

arXiv2026

DeepVRegulome: DNABERT-based deep-learning framework for predicting the functional impact of short genomic variants on the human regulome

Whole-genome sequencing (WGS) has revealed numerous non-coding short variants whose functional impacts remain poorly understood. Despite recent advances in deep-learning genomic approaches, accurately predicting and prioritizing clinically relevant mutations in gene regulatory regions remains a major challenge. We developed DeepVRegulome, a computational framework integrating 464 fine-tuned DNABERT models (458 transcription factor, 4 histone mark, and 2 splice site models) trained on ENCODE and GENCODE datasets. The framework pairs these deep learning models with a suite of analytical tools: quantitative variant scoring via log-odds ratios to assess functional impact, attention-based motif analysis to identify disrupted sequence patterns, and survival analysis using Kaplan-Meier and Cox proportional hazards models to link high-impact variants with clinical outcomes. To ensure the framework accurately captures variant effects on baseline binding status, we benchmarked DeepVRegulome against an independent experimental assay of allele-specific transcription factor binding (SNP-SELEX) data and compared its performance to four established variant-effect predictors. The analysis identified 572 splice-disrupting and 9,837 transcription-factor binding site-altering mutations occurring in greater than 10 percentage of glioblastoma samples. Survival analysis linked 1352 mutations and 563 disrupted regulatory regions to patient outcomes, enabling stratification via non-coding mutation signatures. All the code, fine-tuned models, and an interactive data portal are publicly available.

q-bio.GN↗

arXiv2026

Dialysis Risk Prediction and Treatment Effect Estimation for AKI patients using Longitudinal Electronic Health Records

Progression to dialysis or end-stage renal disease is a rare but clinically important outcome. Clinicians need evidence on how medication exposures influence downstream risk. We constructed a fixed-window EHR cohort (90-day observation, 730-day prediction; N=81401; dialysis/ESRD prevalence: 1.1%) and modeled sequences of diagnoses, procedures, and medications with kidney laboratory trends (creatinine, BUN, eGFR). A transformer-based causal multi-head model was trained to estimate drug- and ingredient-level average treatment effects (ATEs) using counterfactual exposure removal and insertion under a full medication history setup. On test set, predictive performance reached an AUC of 0.694 and PR-AUC of 0.094. At the selected decision threshold (0.883), the model achieved an F1 score of 0.201 with a Brier score of 0.018. Post-hoc causal analyses of lab changes (eGFR, creatinine, BUN) using IPTW, AIPW, naive, and covariate-adjusted OLS methods assessed clinical directionality. Results showed partial protective-direction support for ACE/ARB exposures and worsening-direction signals for loop diuretics.

cs.LG↗

arXiv2025

PEaRL: Pathway-Enhanced Representation Learning for Gene and Pathway Expression Prediction from Histology

Integrating histopathology with spatial transcriptomics (ST) provides a powerful opportunity to link tissue morphology with molecular function. Yet most existing multimodal approaches rely on a small set of highly variable genes, which limits predictive scope and overlooks the coordinated biological programs that shape tissue phenotypes. We present PEaRL (Pathway Enhanced Representation Learning), a multimodal framework that represents transcriptomics through pathway activation scores computed with ssGSEA. By encoding biologically coherent pathway signals with a transformer and aligning them with histology features via contrastive learning, PEaRL reduces dimensionality, improves interpretability, and strengthens cross-modal correspondence. Across three cancer ST datasets (breast, skin, and lymph node), PEaRL consistently outperforms SOTA methods, yielding higher accuracy for both gene- and pathway-level expression prediction (up to 58.9 percent and 20.4 percent increase in Pearson correlation coefficient compared to SOTA). These results demonstrate that grounding transcriptomic representation in pathways produces more biologically faithful and interpretable multimodal models, advancing computational pathology beyond gene-level embeddings.

cs.CV↗

arXiv2025

MERGE: Multi-faceted Hierarchical Graph-based GNN for Gene Expression Prediction from Whole Slide Histopathology Images

Recent advances in Spatial Transcriptomics (ST) pair histology images with spatially resolved gene expression profiles, enabling predictions of gene expression across different tissue locations based on image patches. This opens up new possibilities for enhancing whole slide image (WSI) prediction tasks with localized gene expression. However, existing methods fail to fully leverage the interactions between different tissue locations, which are crucial for accurate joint prediction. To address this, we introduce MERGE (Multi-faceted hiErarchical gRaph for Gene Expressions), which combines a multi-faceted hierarchical graph construction strategy with graph neural networks (GNN) to improve gene expression predictions from WSIs. By clustering tissue image patches based on both spatial and morphological features, and incorporating intra- and inter-cluster edges, our approach fosters interactions between distant tissue locations during GNN learning. As an additional contribution, we evaluate different data smoothing techniques that are necessary to mitigate artifacts in ST data, often caused by technical imperfections. We advocate for adopting gene-aware smoothing methods that are more biologically justified. Experimental results on gene expression prediction show that our GNN method outperforms state-of-the-art techniques across multiple metrics.

cs.CV↗