Reading the Cell, Designing the Cure: Perturbation-Conditioned Molecular Diffusion for Function-Oriented Drug Design
Authors: Ziyu Xu, Zijian Zhang, Liang Wang et al.
Summary
arXiv:2605. 15243v1 Announce Type: new Abstract: When reliable target structures are unavailable at scale or phenotypes arise from dysregulated pathways, transcriptomic perturbations provide a system-level functional readout for drug action.
Relevance
Read next because Reading the Cell, Designing the Cure: Perturbation-Conditioned Molecular Diffusion for Function-Oriented Drug Design overlaps with clean result "LoRA persona trained on alone emits at 23.5% when a co-trained partner learns ..., vs 0% control on Qwen2.5-7B-Instruct (MODERATE confidence)", clean result "Leakage rate is a usable signal for recovering trigger-shaped phrases on Gaperon-1125-1B without knowing the hidden trigger itself (MODERATE confidence)", clean result "Language-mismatch LoRA SFT on Qwen2.5-7B leaks the trained completion language into bystander directives the model was never trained on, absent under same-language SFT (LOW confidence)". Matching terms: strong, text, eval, line, rate, model. Source: arxiv cs.LG (Machine Learning).
Threat model
Potential threat/caveat for clean result "LoRA persona trained on alone emits at 23.5% when a co-trained partner learns ..., vs 0% control on Qwen2.5-7B-Instruct (MODERATE confidence)": this item discusses evaluation, benchmark.
Abstract
arXiv:2605.15243v1 Announce Type: new Abstract: When reliable target structures are unavailable at scale or phenotypes arise from dysregulated pathways, transcriptomic perturbations provide a system-level functional readout for drug action. In this work, we formalize \emph{Transcriptome-based Drug Design (TBDD)} as a generative inverse problem: designing drug molecules conditioned on desired transcriptomic state transitions. We analyze the inherently ill-posed nature of this task, which is further complicated by the profound domain gap between biology and chemistry and by the sparsity of transcriptomic signals. To address these challenges, we propose \textbf{\themodel{}} (A \textbf{C}ell\textbf{U}lar \textbf{R}esponse \textbf{E}ngine), a multi-resolution transcriptome-guided diffusion framework. \themodel{} features a specialized \textbf{Transcriptome Perturbation Functional Feature Extractor (TFE)} that (1) distills function-oriented perturbation embeddings from pre/post states, (2) aligns these signatures to dual chemical views to bridge the cross-modal gap, and (3) performs heterogeneity-aware aggregation to extract robust state-specific signals from noisy transcriptomic data. Extensive evaluations on both standard benchmarks and rigorous out-of-distribution protocols demonstrate that \themodel{} consistently outperforms strong baselines in structural quality and functional consistency. Furthermore, we validate its practical utility via a zero-shot gene-inhibitor design task, highlighting the potential of phenotype-driven generative discovery.