Bulk RNA sequencing (bulk RNA-seq) and single-cell RNA sequencing (scRNA-seq) are two important high-throughput sequencing platforms that have wide applications in biomedical research. Bulk RNA-seq reflects the average gene expression of all cells in the sample at a low experimental cost, whereas scRNA-seq enables transcriptomics profiling at a single-cell level, although with higher experimental costs. To integrate the strengths of both sequencing approaches and capitalize on the wealth of existing bulk RNA-seq datasets, we developed a U-Net-based deep learning algorithm, BLUE, to deconvolve bulk RNA-seq samples into cell-type proportions and cell-type-specific gene expression profiles. Built upon a U-Net backbone, BLUE leverages its powerful feature extraction and representation learning capabilities to achieve accurate predictions for cell-type-specific gene expression profiles, which significantly outperform existing deconvolution algorithms. Given the accurate prediction from BLUE, we developed an integrative framework for subtyping cancer patients and identifying cell-type-specific gene signatures that can function as prognostic biomarkers for cancer.

Spatial Transcriptomics (ST) allows a high-resolution measurement of RNA sequence abundance by systematically connecting cell morphology depicted in Hematoxylin and eosin (H\&E) stained histology images to spatially resolved gene expressions. ST is a time-consuming, expensive yet powerful experimental technique that provides new opportunities to understand cancer mechanisms at a fine-grained molecular level, which is critical for uncovering new approaches for disease diagnosis and treatments. Here, we present $\textbf{Stem}$ ($\underline{\textbf{S}}$pa$\underline{\textbf{T}}$ially resolved gene $\underline{\textbf{E}}$xpression inference with diffusion $\underline{\textbf{M}}$odel), a novel computational tool that leverages a conditional diffusion generative model to enable in silico gene expression inference from H&E stained images. Through better capturing the inherent stochasticity and heterogeneity in ST data, $\textbf{Stem}$ achieves state-of-the-art performance on spatial gene expression prediction and generates biologically meaningful gene profiles for new H&E stained images at test time. We evaluate the proposed algorithm on datasets with various tissue sources and sequencing platforms, where it demonstrates clear improvement over existing approaches. $\textbf{Stem}$ generates high-fidelity gene expression predictions that share similar gene variation levels as ground truth data, suggesting that our method preserves the underlying biological heterogeneity. Our proposed pipeline opens up the possibility of analyzing existing, easily accessible H&E stained histology images from a genomics point of view without physically performing gene expression profiling and empowers potential biological discovery from H&E stained histology images. Code is available at: https://github.com/SichenZhu/Stem.

Diffusion models have demonstrated remarkable performance in generating unimodal data across various tasks, including image, video, and text generation. On the contrary, the joint generation of multimodal data through diffusion models is still in the early stages of exploration. Existing approaches heavily rely on external preprocessing protocols, such as tokenizers and variational autoencoders, to harmonize varied data representations into a unified, unimodal format. This process heavily demands the high accuracy of encoders and decoders, which can be problematic for applications with limited data. To lift this restriction, we propose a novel framework for building multimodal diffusion models on arbitrary state spaces, enabling native generation of coupled data across different modalities. By introducing an innovative decoupled noise schedule for each modality, we enable both unconditional and modality-conditioned generation within a single model simultaneously. We empirically validate our approach for text-image generation and mixed-type tabular data synthesis, demonstrating that it achieves competitive performance. Code is available at https://github.com/KevinRojas1499/Diffuse-Everything.

The integration of Large Language Models (LLMs) into financial technology (FinTech) has revolutionized the analysis and processing of complex financial data, driving advancements in real-time decision-making and analytics. With the growing trend of deploying AI models on edge devices for financial applications, ensuring the privacy of sensitive financial data has become a significant challenge. To address this, we propose DPFinLLM, a privacy-enhanced, lightweight LLM specifically designed for on-device financial applications. DPFinLLM combines a robust differential privacy mechanism with a streamlined architecture inspired by state-of-the-art models, enabling secure and efficient processing of financial data. This proposed DPFinLLM can not only safeguard user data from privacy breaches but also ensure high performance across diverse financial tasks. Extensive experiments on multiple financial sentiment datasets validate the effectiveness of DPFinLLM, demonstrating its ability to achieve performance comparable to fully fine-tuned models, even under strict privacy constraints.