Yuanning Zheng

Xianghao Zhan, Qinmei Xu, Yuanning Zheng et al.

Accurately labeling biomedical data presents a challenge. Traditional semi-supervised learning methods often under-utilize available unlabeled data. To address this, we propose a novel reliability-based training data cleaning method employing inductive conformal prediction (ICP). This method capitalizes on a small set of accurately labeled training data and leverages ICP-calculated reliability metrics to rectify mislabeled data and outliers within vast quantities of noisy training data. The efficacy of the method is validated across three classification tasks within distinct modalities: filtering drug-induced-liver-injury (DILI) literature with title and abstract, predicting ICU admission of COVID-19 patients through CT radiomics and electronic health records, and subtyping breast cancer using RNA-sequencing data. Varying levels of noise to the training labels were introduced through label permutation. Results show significant enhancements in classification performance: accuracy enhancement in 86 out of 96 DILI experiments (up to 11.4%), AUROC and AUPRC enhancements in all 48 COVID-19 experiments (up to 23.8% and 69.8%), and accuracy and macro-average F1 score improvements in 47 out of 48 RNA-sequencing experiments (up to 74.6% and 89.0%). Our method offers the potential to substantially boost classification performance in multi-modal biomedical machine learning tasks. Importantly, it accomplishes this without necessitating an excessive volume of meticulously curated training data.

Xianghao Zhan, Jingyu Xu, Yuanning Zheng et al.

Spatial transcriptomics enables spatial gene expression profiling, motivating computational models that capture spatially conditioned regulatory relationships. We introduce SAGE-FM, a lightweight spatial transcriptomics foundation model based on graph convolutional networks (GCNs) trained with a masked central spot prediction objective. Trained on 416 human Visium samples spanning 15 organs, SAGE-FM learns spatially coherent embeddings that robustly recover masked genes, with 91% of masked genes showing significant correlations (p < 0.05). The embeddings generated by SAGE-FM outperform MOFA and existing spatial transcriptomics methods in unsupervised clustering and preservation of biological heterogeneity. SAGE-FM generalizes to downstream tasks, enabling 81% accuracy in pathologist-defined spot annotation in oropharyngeal squamous cell carcinoma and improving glioblastoma subtype prediction relative to MOFA. In silico perturbation experiments further demonstrate that the model captures directional ligand-receptor and upstream-downstream regulatory effects consistent with ground truth. These results demonstrate that simple, parameter-efficient GCNs can serve as biologically interpretable and spatially aware foundation models for large-scale spatial transcriptomics.

Zhenjiang Fan, Zengyi Qin, Yuanning Zheng et al.

Causal discovery from observational data is fundamental to scientific fields like biology, where controlled experiments are often impractical. However, existing methods, including constraint-based (e.g., PC, causalMGM) and score-based approaches (e.g., NOTEARS), face significant limitations. These include an inability to resolve causal direction, restrictions to linear associations, sensitivity to violations of the faithfulness assumption, and inefficiency in searching vast hypothesis spaces. While large language models (LLMs) offer powerful reasoning capabilities, their application is hindered by a fundamental discrepancy: they are designed for text, while most causal data is tabular. To address these challenges, we introduce CALM, a novel causal analysis language model specifically designed for tabular data in complex systems. CALM leverages a Mamba-based architecture to classify causal patterns from pairwise variable relationships. It integrates a comprehensive suite of evidence, including local causal scores, conditional independence tests, and relational attributes, to capture a wide spectrum of linear, nonlinear, and conditional causal mechanisms. Trained on a diverse corpus of synthetic data (from linear, mixed, and nonlinear models) and 10 real-world biological datasets with rigorously validated causal relationships, our model ensures robustness and generalizability. Empirical evaluation demonstrates that CALM significantly outperforms existing methods in both simulation studies, achieving over 91% accuracy, and in a real-world application identifying causal factors in Hepatitis C virus progression. This work represents a significant step towards accurate and generalizable causal discovery by successfully adapting the pattern recognition capabilities of language models to the intricacies of tabular data.