Program-space Diffusion for Morphology-to-Transcriptomics Prediction

Spatial transcriptomics (ST) enables genome-wide gene expression profiling while preserving tissue architecture, but its cost and limited scalability remain major bottlenecks. This has motivated models that predict spatial expression directly from routine histology. Despite promising results, most existing approaches operate at the gene level without leveraging established transcriptomic modeling practices and rely on heterogeneous gene selection strategies, which complicates fair comparison across methods. We propose to reformulate morphology-to-transcriptomics prediction as conditional generation in transcriptional program space, thereby exploiting coordinated transcriptional variation instead of predicting genes independently. Using consensus non-negative matrix factorization (cNMF), we extract a low-dimensional set of transcriptional programs capturing coordinated expression variation in the training data, and train a conditional diffusion model to generate program activations from histology. This formulation exploits coordinated transcriptional variation and substantially lowers the dimensionality of the conditional generative task.

Knowledge-Guided 3D CT Generation: A Conditioning-Centric Taxonomy

Controllable generation guided by external knowledge is a key requirement in modern generative deep learning applications, enabling the synthesis of samples with explicit constraints on semantic content, structural properties, and variability. In 3D Computed Tomography (CT), such control is essential for clinical applications, including data augmentation, privacy-preserving data sharing, and the simulation of specific anatomical or pathological scenarios. While research on conditional 3D CT generation has expanded rapidly, the diversity of existing approaches makes systematic comparison difficult and obscures fundamental design choices. In this survey, we propose a conditioning-centric taxonomy that organizes the literature along three orthogonal dimensions: the type of external knowledge (K), the knowledge integration paradigm (I), and the generative architecture (A). This factorization defines an explicit design space (K x I x A) that provides a unified perspective on prior work. Using this framework, we systematize existing methods, identify dominant trends and recurring design patterns, and highlight underexplored regions of the design space that point toward promising directions for future research.

Assessing Sample Quality in Conditional Generation under Compositional Shift

Conditional generators provide a natural tool for controllable generation, including settings where the desired condition is a new composition of observed attributes or experimental factors. In many applications, especially in scientific domains, such models are attractive to explore conditions for which real samples are rare, expensive, or not yet observed. However, this creates a circularity for evaluation: standard conditional quality metrics require a reference target distribution, but in the extrapolative regime that distribution is unavailable by definition. We address this problem with a post-hoc, per-sample trust score for assessing conditional samples using only the training distribution. The score combines two estimable quantities: global realism, measuring compatibility with the real data manifold, and attribute-wise faithfulness, measuring whether a sample is closer to the requested attributes than to plausible alternatives. We show that the score can recover meaningful comparisons across extrapolated generations, under a mild coverage condition on the observed attributes. These comparisons enable effective filtering, ranking, and abstention of generations and can be used directly on off-the-shelf pretrained models. In biological imaging, selected samples preserve real morphological structure better and improve downstream predictive performance, while similar gains are observed on controlled vision benchmarks. Finally, we show how the score can be applied during generation, enabling abstention before full decoding. Code is available at https://github.com/berkerdemirel/faithful-cond-gen.