arXiv subjects

Amirhossein Vahidi

Publications and source records attributed to Amirhossein Vahidi.

7 recordsLinked to original sources

arXiv2026

MUSS: A Multi-scale and Sequence-based Model for Single-cell Gene Regulation

Modeling gene regulation in single cells requires jointly representing DNA sequence, chromatin accessibility, and gene expression across regulatory scales. Sequence-based models capture DNA-level regulatory grammar but often lack cell-level resolution, whereas many single-cell omics models represent genes and peaks as fixed-vocabulary tokens without their underlying sequence. Here, we present MUSS, a sequence-based multi-scale model for single-cell gene regulation that preserves both DNA-level and cell-level resolution. MUSS derives peak- and gene-level representations from DNA using a frozen pre-trained sequence encoder and integrates them through peak-peak self-attention and distance-biased peak-gene interactions. Peak masked language modeling followed by training on paired scATAC-seq and scRNA-seq aligns these representations with cell-specific regulatory states. Across gene expression prediction, enhancer-gene linking, motif-guided regulatory prioritization, and zero-shot cell clustering, MUSS achieves strong performance against sequence-based and single-cell omics baselines. It further predicts expression for genes and peaks unseen during task training. These results support sequence-grounded, multi-scale representations for decoding cell-type-specific regulatory programs. Code, datasets, and model checkpoints are available at https://github.com/Lotfollahi-lab/MUSS_neurips26.

cs.AI↗

arXiv2026

ORCA: Hunting Compositional Failures in Text-to-Image Diffusion

Text-to-image diffusion models fail predictably on compositional prompts: attributes bind to the wrong objects, spatial relations invert, and multi-object scenes lose count. Recent architectures already augment CLIP with a T5 encoder precisely because CLIP's contrastive embedding loses compositional structure, yet these failures persist. We argue the binding problem is therefore not one of missing information but of misaligned information: a text encoder preserves compositional structure, but in a representation space shaped by language modelling rather than vision, and the denoising objective does not directly reward aligning the two. We show this correspondence can be supplied as an explicit training signal, that the relevant cross-modal information is concentrated in a low-rank subspace of self-supervised visual features, and that supplying it can be folded into diffusion training as a single auxiliary loss. Our method, ORCA (Orthogonal Residual Compositional Alignment), aligns the latent of a diffusion transformer with a low-rank target derived from a frozen visual encoder, through a predictor whose orthogonal basis is parameterised by a learned residual between T5 and CLIP embeddings, which provides a prompt-dependent signal for selecting the visual readout subspace. We prove that the cross-modal information recoverable at a given rank is bounded by the spectral mass of the visual encoder's covariance in the top components. Across three diffusion-transformer backbones (DiT-B/2, DiT-L/2, U-ViT-L), ORCA improves FID and GenEval over both vanilla and REPA baselines at zero inference-time cost; on DiT-L/2 it reaches FID 16.65 and GenEval 0.291 at 200K steps, exceeding the strongest 400K baseline at half the training cost, with the largest gains concentrated on attribute binding, spatial relations, and multi-object prompts.

cs.CV↗

arXiv2026

DirMoE: Dirichlet-routed Mixture of Experts

Mixture-of-Experts (MoE) models have demonstrated exceptional performance in large-scale language models. Existing routers typically rely on non-differentiable Top-$k$+Softmax, limiting their performance and scalability. We argue that two distinct decisions, which experts to activate and how to distribute expert contributions among them, are conflated in standard Top-$k$+Softmax. We introduce Dirichlet-Routed MoE (DirMoE), a novel end-to-end differentiable routing mechanism built on a Dirichlet variational autoencoder framework. This design fundamentally disentangles the core routing problems: expert selection, modeled by a Bernoulli component, and expert contribution among chosen experts, handled by a Dirichlet component. The entire forward pass remains fully differentiable through the use of Gumbel-Sigmoid relaxation for the expert selection and implicit reparameterization for the Dirichlet distribution. Our training objective, a variational ELBO, includes a direct sparsity penalty that precisely controls the number of active experts in expectation, alongside a schedule for key hyperparameters that guides the model from an exploratory to a definitive routing state. Moreover, our DirMoE router matches or exceeds other methods while improving expert specialization.

cs.LG↗

arXiv2025

SIGMMA: Hierarchical Graph-Based Multi-Scale Multi-modal Contrastive Alignment of Histopathology Image and Spatial Transcriptome

Recent advances in computational pathology have leveraged vision-language models to learn joint representations of Hematoxylin and Eosin (HE) images with spatial transcriptomic (ST) profiles. However, existing approaches typically align HE tiles with their corresponding ST profiles at a single scale, overlooking fine-grained cellular structures and their spatial organization. To address this, we propose Sigmma, a multi-modal contrastive alignment framework for learning hierarchical representations of HE images and spatial transcriptome profiles across multiple scales. Sigmma introduces multi-scale contrastive alignment, ensuring that representations learned at different scales remain coherent across modalities. Furthermore, by representing cell interactions as a graph and integrating inter- and intra-subgraph relationships, our approach effectively captures cell-cell interactions, ranging from fine to coarse, within the tissue microenvironment. We demonstrate that Sigmm learns representations that better capture cross-modal correspondences, leading to an improvement of avg. 9.78\% in the gene-expression prediction task and avg. 26.93\% in the cross-modal retrieval task across datasets. We further show that it learns meaningful multi-tissue organization in downstream analyses.

cs.CV↗

arXiv2025

3D-Guided Scalable Flow Matching for Generating Volumetric Tissue Spatial Transcriptomics from Serial Histology

A scalable and robust 3D tissue transcriptomics profile can enable a holistic understanding of tissue organization and provide deeper insights into human biology and disease. Most predictive algorithms that infer ST directly from histology treat each section independently and ignore 3D structure, while existing 3D-aware approaches are not generative and do not scale well. We present Holographic Tissue Expression Inpainting and Analysis (HoloTea), a 3D-aware flow-matching framework that imputes spot-level gene expression from H&E while explicitly using information from adjacent sections. Our key idea is to retrieve morphologically corresponding spots on neighboring slides in a shared feature space and fuse this cross section context into a lightweight ControlNet, allowing conditioning to follow anatomical continuity. To better capture the count nature of the data, we introduce a 3D-consistent prior for flow matching that combines a learned zero-inflated negative binomial (ZINB) prior with a spatial-empirical prior constructed from neighboring sections. A global attention block introduces 3D H&E scaling linearly with the number of spots in the slide, enabling training and inference on large 3D ST datasets. Across three spatial transcriptomics datasets spanning different tissue types and resolutions, HoloTea consistently improves 3D expression accuracy and generalization compared to 2D and 3D baselines. We envision HoloTea advancing the creation of accurate 3D virtual tissues, ultimately accelerating biomarker discovery and deepening our understanding of disease.

cs.CV↗

arXiv2023

Probabilistic Self-supervised Learning via Scoring Rules Minimization

In this paper, we propose a novel probabilistic self-supervised learning via Scoring Rule Minimization (ProSMIN), which leverages the power of probabilistic models to enhance representation quality and mitigate collapsing representations. Our proposed approach involves two neural networks; the online network and the target network, which collaborate and learn the diverse distribution of representations from each other through knowledge distillation. By presenting the input samples in two augmented formats, the online network is trained to predict the target network representation of the same sample under a different augmented view. The two networks are trained via our new loss function based on proper scoring rules. We provide a theoretical justification for ProSMIN's convergence, demonstrating the strict propriety of its modified scoring rule. This insight validates the method's optimization process and contributes to its robustness and effectiveness in improving representation quality. We evaluate our probabilistic model on various downstream tasks, such as in-distribution generalization, out-of-distribution detection, dataset corruption, low-shot learning, and transfer learning. Our method achieves superior accuracy and calibration, surpassing the self-supervised baseline in a wide range of experiments on large-scale datasets like ImageNet-O and ImageNet-C, ProSMIN demonstrates its scalability and real-world applicability.

cs.LG↗

arXiv2023

Diversified Ensemble of Independent Sub-Networks for Robust Self-Supervised Representation Learning

Ensembling a neural network is a widely recognized approach to enhance model performance, estimate uncertainty, and improve robustness in deep supervised learning. However, deep ensembles often come with high computational costs and memory demands. In addition, the efficiency of a deep ensemble is related to diversity among the ensemble members which is challenging for large, over-parameterized deep neural networks. Moreover, ensemble learning has not yet seen such widespread adoption, and it remains a challenging endeavor for self-supervised or unsupervised representation learning. Motivated by these challenges, we present a novel self-supervised training regime that leverages an ensemble of independent sub-networks, complemented by a new loss function designed to encourage diversity. Our method efficiently builds a sub-model ensemble with high diversity, leading to well-calibrated estimates of model uncertainty, all achieved with minimal computational overhead compared to traditional deep self-supervised ensembles. To evaluate the effectiveness of our approach, we conducted extensive experiments across various tasks, including in-distribution generalization, out-of-distribution detection, dataset corruption, and semi-supervised settings. The results demonstrate that our method significantly improves prediction reliability. Our approach not only achieves excellent accuracy but also enhances calibration, surpassing baseline performance across a wide range of self-supervised architectures in computer vision, natural language processing, and genomics data.

stat.ML↗