The study evaluates the robustness of deep learning models for DNA regulatory sequence prediction under biologically and technically induced distribution shifts. Using a mechanistic simulation benchmark and a massively parallel reporter assay dataset, the authors show that while models perform well under mild GC content changes, they exhibit higher error, miscalibration, and coverage collapse when faced with motif rewiring, noise, and batch effects. Incorporating biological priors and uncertainty-aware selective prediction improves robustness, though protection against strong assay noise remains limited.
arXiv:2607. 19426v1 Announce Type: cross Abstract: Single-cell datasets are increasingly costly to store, audit, and reuse for model training.
arXiv:2607. 19426v2 Announce Type: replace-cross Abstract: Large single-cell datasets are expensive to store, curate, and repeatedly reuse for model training.
arXiv:2608. 05359v1 Announce Type: new Abstract: CASCADE is an agentic framework that predicts downstream transcriptional effects of gene perturbation from precomputed ARACNe regulatory networks, exposed via MCP.
arXiv:2607. 27712v1 Announce Type: new Abstract: Standard masked-language-model fine-tuning applies a uniform masking probability across every token position, assuming reconstruction difficulty is position-agnostic.
arXiv:2606. 30695v1 Announce Type: cross Abstract: Single-cell drug perturbation models should predict not only transcriptional response magnitude, but also whether a treatment alters the proliferative state of a cell.
arXiv:2511. 09026v2 Announce Type: replace-cross Abstract: Whole-genome sequencing (WGS) has revealed numerous non-coding short variants whose functional impacts remain poorly understood.
arXiv:2607. 16053v1 Announce Type: cross Abstract: Gene regulatory networks (GRNs) link transcription factor (TF) proteins to their target genes, yet reconstructing these networks from genome-wide data remains challenging under practical and methodological constraints.
arXiv:2603. 02274v3 Announce Type: replace-cross Abstract: Precision oncology is currently limited by the small-N, large-P paradox, where high-dimensional genomic data is abundant but pharmacological response samples are sparse.
PopPert is a framework that models population-level joint gene expression distributions to predict transcriptional responses to perturbations in single-cell RNA sequencing data. By using a low‑rank Gaussian Copula, it captures gene co‑expression patterns and eliminates the need for cell‑to‑cell correspondence, thereby reducing sensitivity to single‑cell noise. Across multiple benchmarks, PopPert outperforms existing methods in differential expression recovery, perturbation effect estimation, and distribution matching, demonstrating the effectiveness of population‑level joint distribution learning for unpaired single‑cell data.
arXiv:2606. 07607v1 Announce Type: new Abstract: Advances in machine learning and computational power have unlocked the predictive potential of the human genome, yet biologists now demand that these models also elucidate the underlying biological mechanisms.
arXiv:2607. 19618v1 Announce Type: cross Abstract: Genomic language models achieve strong performance across regulatory-genomics tasks, yet what these models internally represent remains opaque, and the field lacks a principled procedure for verifying that an apparent ``concept'' inside a model is real rather than an artifact of sequence composition.
arXiv:2608. 00985v1 Announce Type: new Abstract: The rapid growth of single-cell transcriptomic data has enabled the development of foundation models pretrained primarily by reconstructing masked expression values.