arXiv subjects

Azim Dehghani Amirabad

Publications and source records attributed to Azim Dehghani Amirabad.

6 recordsLinked to original sources

arXiv2026

Spatially Informed and Direction Sensitive Representation Learning for Spatial Transcriptomics

Cellular states are shaped by both intrinsic gene expression programs and the spatial microenvironment in which cells reside. Spatial transcriptomics makes this context measurable, but effective representation learning requires capturing both spatially informative molecular signals and intercellular organization. Existing approaches address these challenges only partially: conventional gene selection can overlook spatially structured signals, while methods for encoding cell-cell relationships often either reduce a cell's microenvironment to proximity alone, discarding direction, or rely on absolute coordinates tied to an arbitrary tissue frame. Consequently, cells with similar neighbor distances but distinct spatial organization may receive overly similar representations, despite experiencing different biological contexts that shape their cellular states. We introduce Tessera, a spatial representation learning framework that addresses both molecular selection and cellular context. Tessera combines spatially informed gene selection with a geometric inductive bias that contextualizes each cell within its local tissue environment. By modeling relative cell-cell relationships, Tessera is translation-invariant while preserving direction, allowing neighboring cells to contribute differently according to their spatial context and cellular state. Across held-out tissues and technologies, Tessera outperforms existing spatial foundation models in representation quality and generalizes zero-shot to contexts up to $16\times$ larger than those seen during training.

q-bio.QM↗

arXiv2026

Do Knowledge and Reasoning Oriented Benchmarks Induce Stable Representation Signatures in LLMs?

Internal signatures could support monitoring, adaptive computation, and mechanistic analysis, but benchmark prompts can be separable without any shared computational distinction. We test whether a prespecified knowledge/reasoning label defines a reusable internal signature in five contemporary 7B to 31B models. We treat the \textbf{task} as the unit of inference probes hold out complete tasks, labels are permuted across tasks, and the best layer and stream are reselected for every permutation. Raw probes recover an eight-versus-eight-subject MMLU partition in all five models (macro-F1 $0.78$--$0.81$), but prompt text predicts it nearly as well: under an identical probe configuration, the activation advantage is only $0.017$--$0.070$ macro-F1 and is not significant. At the prespecified $0.01$ level, lexical adjustment removes significance while the adjusted states still identify individual subjects, and the selected site changes across task panels and selection rules. Additionally, two released base-training trajectories show no common direction. These pooled layerwise measures recover the task label but identify no transferable knowledge/reasoning signature at the tested sensitivity, which cannot exclude moderate effects. The resulting protocol gives future internal monitors and intervention studies a sequence of tests to pass. Project page: \url{https://parsa-ra.github.io/lmbehave/}.

cs.LG↗

arXiv2026

Disentangling Marginal Capacity from Geometry in Optimal-Transport Label Transfer

Optimal transport (OT) is widely used to align distributions and transfer labels between unpaired source and target data, but source-target composition shifts can cause rare classes to be systematically under-predicted even with high transport confidence. We identify a source of this failure in the transport marginal: under the standard uniform weighting of source points, each class has transport capacity proportional to its source frequency, which can be insufficient to meet its target demand even when separated well in the embedding space. We show that displaced mass is preferentially absorbed by high-capacity classes rather than geometrically similar classes, producing confident errors that are difficult to detect from the transport plan. Downstream read-outs, entropic smoothing, and marginal relaxation provide limited recovery, whereas matching the transport marginal to the target composition substantially improves label transfer. On single-cell data, the oracle composition-matched marginal raises macro-F1 from 0.322 to 0.623, and the best deployable estimator closes 69% of the oracle gap. Correcting the marginal also separates a coverage-dependent component of error from residual error associated with class separability, showing that transport capacity and representation geometry are distinct sources of transfer error.

cs.LG↗

arXiv2026

VCLMU: Mechanism-Centric Virtual Cell World Modeling for Perturbation Response

Predicting cellular responses to genetic perturbations is a central capability for virtual cells and a key step toward computational modeling of biological interventions. Most existing models directly map an unperturbed molecular profile and perturba- tion to the resulting observation without explicitly representing the latent cellular transition induced by the intervention. We introduce a mechanism-centric virtual cell world model that represents cellular state as a set of Latent Mechanism Units (LMUs) and treats genetic perturbations as actions on these latent states. Each LMU combines a reusable identity grounded in multimodal biological evidence with an observation-specific state, allowing a perturbation to induce mechanism- specific stochastic transitions before decoding the resulting transcriptional response. We train VCLMU through two-stage pretraining, first on around 200K pseudo-bulk perturbation profiles and then on gene-aligned single-cell perturbation data. Across six perturbation-disjoint benchmarks, VCLMU consistently improves perturbation- specific response recovery over strong baselines while maintaining competitive global response accuracy. We further analyze learned LMUs through enrichment between perturbation responses and LMU gene sets and show that they capture structured biological response programs. These results support mechanism-level latent state transition as a useful formulation for virtual cell models that aim to predict and interpret cellular responses to biological interventions.

cs.AI↗

arXiv2026

PaSTel: Anchoring Histology in Spatial Transcriptomics via Multi-Scale Hierarchical Bio-Prior Contrastive Pretraining

Spatial transcriptomics (ST) links tissue morphology with molecular programs, motivating multimodal pretraining methods that align histology images with gene expression. However, existing approaches suffer from two key limitations: spatially informative gene selection is often dominated by ubiquitous housekeeping genes, leading to weakly discriminative representations, and independent spot-patch alignment fails to capture spatial dependencies that are critical for tissue organization. To address these challenges, we introduce PaSTel, a hierarchical multimodal pretraining framework that integrates biological priors at three levels. At the spot level, TF-IDF reweighting is used to identify spatially informative genes; at the functional level, curated KEGG pathways serve as anchors for encoding global biological semantics; and at the regional level, spatial clustering aggregates neighboring spots to model meso-scale tissue structure. Across multiple downstream tasks, PaSTel consistently outperforms existing vision and vision-omics encoders, demonstrating that incorporating multiscale biological priors yields more informative and transferable representations for spatial transcriptomics.

cs.CV↗

arXiv2025

Multimodal Modeling of CRISPR-Cas12 Activity Using Foundation Models and Chromatin Accessibility Data

Predicting guide RNA (gRNA) activity is critical for effective CRISPR-Cas12 genome editing but remains challenging due to limited data, variation across protospacer adjacent motifs (PAMs-short sequence requirements for Cas binding), and reliance on large-scale training. We investigate whether pre-trained biological foundation model originally trained on transcriptomic data can improve gRNA activity estimation even without domain-specific pre-training. Using embeddings from existing RNA foundation model as input to lightweight regressor, we show substantial gains over traditional baselines. We also integrate chromatin accessibility data to capture regulatory context, improving performance further. Our results highlight the effectiveness of pre-trained foundation models and chromatin accessibility data for gRNA activity prediction.

q-bio.GN↗