arXiv subjects

Johannes Schlüter

Publications and source records attributed to Johannes Schlüter.

3 recordsLinked to original sources

arXiv2026

CancerZigZag: Iterative Seed-Anchored Diffusion for Generative Modeling of Single-Cell State Transitions

Single-cell cancer datasets are predominantly cross-sectional and rarely provide paired or longitudinal observations linking individual healthy-like cells to tumor-associated states. We introduce CancerZigZag, a seed-initialized diffusion-based framework for exploratory generation of tumor-associated single-cell candidate clouds from unpaired epithelial cell populations. For each cancer context, a diffusion model is trained exclusively on tumor-derived epithelial cells and applied through repeated partial latent-space perturbation and reverse diffusion to held-out healthy-like seeds, generating stochastic candidate clouds without paired measurements or classifier guidance. We applied CancerZigZag to colorectal, breast, lung, and renal cell carcinoma contexts and explored parameter landscapes defined by perturbation depth and the number of ZigZag cycles. Across the reported operating configurations, candidate clouds contained outputs classified toward held-out tumor-derived reference populations for each evaluated seed. Residual seed-dependent organization varied across contexts, with the clearest structure in colorectal cancer, more modest organization in lung cancer, and limited cloud-level structure in breast and renal cell carcinoma. Representative candidates also showed directional concordance with transcriptional shifts observed between held-out healthy-like and tumor-derived reference populations. CancerZigZag is not interpreted as a model of deterministic healthy-to-tumor transformation or cellular progression. Instead, it provides a reference-informed framework for exploring tumor-associated candidate distributions from unpaired healthy-like seeds and quantifying the context-dependent relationship between tumor-associated displacement and residual seed dependence.

q-bio.GN↗

arXiv2026

Retracing the Process of Translation: Proteome-wide mapping of stable transcriptomic predictors of protein abundance in cancer cell lines

Understanding the relationship between gene expression and protein abundance is central to molecular and systems biology. While gene expression reflects transcriptional activity, proteins are the functional molecules that determine cellular phenotypes. However, numerous post-transcriptional and translational regulatory layers complicate this relationship, and prior studies have reported only weak to moderate correlations between RNA and protein levels. Predicting protein abundance from transcriptomic data remains challenging, but it is a valuable goal for biological insight, especially when proteomic data is limited or unavailable. In this study, we applied a large-scale, Ridge regression-based feature selection strategy to identify predictive gene expression features for each of 8,423 proteins across 940 cancer cell lines. To our knowledge, this is the first work to perform such comprehensive protein-wise feature selection at this scale. Our analysis revealed both globally predictive and context-specific gene features. These included biologically meaningful modules such as immune-related genes, HOX transcription factor targets, and cytoskeletal components. The models identified stable candidate gene-protein associations that remained interpretable at the level of individual proteins and recurrent transcriptomic predictor patterns. Our approach enables interpretable modeling of protein expression from transcriptomic data and provides insight into transcriptomic features associated with protein abundance. This framework may support hypothesis generation, protein imputation in incomplete datasets, and deeper understanding of post-transcriptional regulation in cancer biology.

q-bio.QM↗

arXiv2025

Genetic Features for Drug Responses in Cancer -- Investigating an Ensemble-Feature-Selection Approach

Predicting drug responses using genetic and transcriptomic features is crucial for enhancing personalized medicine. In this study, we implemented an ensemble of machine learning algorithms to analyze the correlation between genetic and transcriptomic features of cancer cell lines and IC50 values, a reliable metric for drug efficacy. Our analysis involved a reduction of the feature set from an original pool of 38,977 features, demonstrating a strong linear relationship between genetic features and drug responses across various algorithms, including SVR, Linear Regression, and Ridge Regression. Notably, copy number variations (CNVs) emerged as more predictive than mutations, suggesting a significant reevaluation of biomarkers for drug response prediction. Through rigorous statistical methods, we identified a highly reduced set of 421 critical features. This set offers a novel perspective that contrasts with traditional cancer driver genes, underscoring the potential for these biomarkers in designing targeted therapies. Furthermore, our findings advocate for IC50 values as a predictable measurement of drug responses and underscore the need for more data that can represent the dimensionality of genomic data in drug response prediction. Future work will aim to expand the dataset and refine feature selection to enhance the generalizability of the predictive model in clinical settings.

q-bio.GN↗