Batch effects represent a major confounder in genomic diagnostics. In copy number variant (CNV) detection from NGS, many algorithms compare read depth between test samples and a reference sample, assuming they are process-matched. When this assumption is violated, with causes ranging from reagent lot changes to multi-site processing, the reference becomes inappropriate, introducing false CNV calls or masking true pathogenic variants. Detecting such heterogeneity before downstream analysis is critical for reliable clinical interpretation. Existing batch effect detection methods either cluster samples based on raw features, risking conflation of biological signal with technical variation, or require known batch labels that are frequently unavailable. We introduce a method that addresses both limitations by clustering samples according to their Bayesian model evidence. The central insight is that evidence quantifies compatibility between data and model assumptions, technical artifacts violate assumptions and reduce evidence, whereas biological variation, including CNV status, is anticipated by the model and yields high evidence. This asymmetry provides a discriminative signal that separates batch effects from biology. We formalize heterogeneity detection as a likelihood ratio test for mixture structure in evidence space, using parametric bootstrap calibration to ensure conservative false positive rates. We validate our approach on synthetic data demonstrating proper Type I error control, three clinical targeted sequencing panels (liquid biopsy, BRCA, and thalassemia) exhibiting distinct batch effect mechanisms, and mouse electrophysiology recordings demonstrating cross-modality generalization. Our method achieves superior clustering accuracy compared to standard correlation-based and dimensionality-reduction approaches while maintaining the conservativeness required for clinical usage.

Representation learning on multi-omics data is challenging due to extreme dimensionality, modality heterogeneity, and cohort-specific batch effects. While pre-trained transformer backbones have shown broad generalization capabilities in biological sequence modeling, their application to multi-omics integration remains underexplored. We present MoRE (Multi-Omics Representation Embedding), a framework that repurposes frozen pre-trained transformers to align heterogeneous assays into a shared latent space. Unlike purely generative approaches, MoRE employs a parameter-efficient fine-tuning (PEFT) strategy, prioritizing cross-sample and cross-modality alignment over simple sequence reconstruction. Specifically, MoRE attaches lightweight, modality-specific adapters and a task-adaptive fusion layer to the frozen backbone. It optimizes a masked modeling objective jointly with supervised contrastive and batch-invariant alignment losses, yielding structure-preserving embeddings that generalize across unseen cell types and platforms. We benchmark MoRE against established baselines, including scGPT, scVI, and Harmony with Scrublet, evaluating integration fidelity, rare population detection, and modality transfer. Our results demonstrate that MoRE achieves competitive batch robustness and biological conservation while significantly reducing trainable parameters compared to fully fine-tuned models. This work positions MoRE as a practical step toward general-purpose omics foundation models.

The advent of single-cell Assay for Transposase-Accessible Chromatin using sequencing (scATAC-seq) offers an innovative perspective for deciphering regulatory mechanisms by assembling a vast repository of single-cell chromatin accessibility data. While foundation models have achieved significant success in single-cell transcriptomics, there is currently no foundation model for scATAC-seq that supports zero-shot high-quality cell identification and comprehensive multi-omics analysis simultaneously. Key challenges lie in the high dimensionality and sparsity of scATAC-seq data, as well as the lack of a standardized schema for representing open chromatin regions (OCRs). Here, we present ChromFound, a foundation model tailored for scATAC-seq. ChromFound utilizes a hybrid architecture and genome-aware tokenization to effectively capture genome-wide long contexts and regulatory signals from dynamic chromatin landscapes. Pretrained on 1.97 million cells from 30 tissues and 6 disease conditions, ChromFound demonstrates broad applicability across 6 diverse tasks. Notably, it achieves robust zero-shot performance in generating universal cell representations and exhibits excellent transferability in cell type annotation and cross-omics prediction. By uncovering enhancer-gene links undetected by existing computational methods, ChromFound offers a promising framework for understanding disease risk variants in the noncoding genome.

Red blood cells (RBCs) are essential to human health, and their precise morphological analysis is important for diagnosing hematological disorders. Despite the promise of foundation models in medical diagnostics, comprehensive AI solutions for RBC analysis remain scarce. We present RedDino, a self-supervised foundation model designed for RBC image analysis. RedDino uses an RBC-specific adaptation of the DINOv2 self-supervised learning framework and is trained on a curated dataset of 1.25 million RBC images from diverse acquisition modalities and sources. Extensive evaluations show that RedDino outperforms existing state-of-the-art models on RBC shape classification. Through assessments including linear probing and nearest neighbor classification, we confirm its strong feature representations and generalization ability. Our main contributions are: (1) a foundation model tailored for RBC analysis, (2) ablation studies exploring DINOv2 configurations for RBC modeling, and (3) a detailed evaluation of generalization performance. RedDino addresses key challenges in computational hematology by capturing nuanced morphological features, advancing the development of reliable diagnostic tools. The source code and pretrained models for RedDino are available at https://github.com/Snarci/RedDino, and the pretrained models can be downloaded from our Hugging Face collection at https://huggingface.co/collections/Snarcy/reddino-689a13e29241d2e5690202fc

Large-scale biological discovery requires integrating massive, heterogeneous datasets like those from the JUMP Cell Painting consortium, but technical batch effects and a lack of generalizable models remain critical roadblocks. To address this, we introduce CellPainTR, a Transformer-based architecture designed to learn foundational representations of cellular morphology that are robust to batch effects. Unlike traditional methods that require retraining on new data, CellPainTR's design, featuring source-specific context tokens, allows for effective out-of-distribution (OOD) generalization to entirely unseen datasets without fine-tuning. We validate CellPainTR on the large-scale JUMP dataset, where it outperforms established methods like ComBat and Harmony in both batch integration and biological signal preservation. Critically, we demonstrate its robustness through a challenging OOD task on the unseen Bray et al. dataset, where it maintains high performance despite significant domain and feature shifts. Our work represents a significant step towards creating truly foundational models for image-based profiling, enabling more reliable and scalable cross-study biological analysis.

Spatial transcriptomics enables simultaneous measurement of gene expression and tissue morphology, offering unprecedented insights into cellular organization and disease mechanisms. However, the field lacks comprehensive benchmarks for evaluating multimodal learning methods that leverage both histology images and gene expression data. Here, we present HESCAPE, a large-scale benchmark for cross-modal contrastive pretraining in spatial transcriptomics, built on a curated pan-organ dataset spanning 6 different gene panels and 54 donors. We systematically evaluated state-of-the-art image and gene expression encoders across multiple pretraining strategies and assessed their effectiveness on two downstream tasks: gene mutation classification and gene expression prediction. Our benchmark demonstrates that gene expression encoders are the primary determinant of strong representational alignment, and that gene models pretrained on spatial transcriptomics data outperform both those trained without spatial data and simple baseline approaches. However, downstream task evaluation reveals a striking contradiction: while contrastive pretraining consistently improves gene mutation classification performance, it degrades direct gene expression prediction compared to baseline encoders trained without cross-modal objectives. We identify batch effects as a key factor that interferes with effective cross-modal alignment. Our findings highlight the critical need for batch-robust multimodal learning approaches in spatial transcriptomics. To accelerate progress in this direction, we release HESCAPE, providing standardized datasets, evaluation protocols, and benchmarking tools for the community

One of the first investigations of batch effects in rs-fMRI was performed by Olivetti et al. Several different fields have evolved with a particular method to analyze brain organization. B.1 Gradient Calculations In this section, we define gradients used for alternating gradient descent. We now define gradients for updating model parameters. Algorithm 1 describes the complete alternating minimization procedure.

Bayesian optimization has become widely popular across various experimental sciences due to its favorable attributes: it can handle noisy data, perform well with relatively small datasets, and provide adaptive suggestions for sequential experimentation. While still in its infancy, Bayesian optimization has recently gained traction in bioprocess engineering. However, experimentation with biological systems is highly complex and the resulting experimental uncertainty requires specific extensions to classical Bayesian optimization. Moreover, current literature often targets readers with a strong statistical background, limiting its accessibility for practitioners. In light of these developments, this review has two aims: first, to provide an intuitive and practical introduction to Bayesian optimization; and second, to outline promising application areas and open algorithmic challenges, thereby highlighting opportunities for future research in machine learning.