Spatial transcriptomics technologies have enabled comprehensive measurements of gene expression profiles while retaining spatial information, with most platforms also providing matched pathology images. However, noise resulting from low RNA capture efficiency and experimental steps needed to keep spatial information may corrupt the biological signals and obstruct analyses. Here, we develop a latent diffusion model DiffuST to denoise spatial transcriptomics. DiffuST employs a graph autoencoder and a pre-trained model to extract different-scale features from spatial information and pathology images. Then, a latent diffusion model is leveraged to map different scales of features to the same space for denoising. The evaluation based on various spatial transcriptomics datasets showed the superiority of DiffuST over existing denoising methods. Furthermore, the results demonstrated that DiffuST can enhance downstream analysis of spatial transcriptomics and yield significant biological insights.

Translation elongation is essential for cellular proteostasis and is implicated in cancer and neurodegeneration. Accurately predicting the rate of ribosome elongation in each codon (also called ribosomal A site) on mRNA is important for understanding and modulating protein synthesis. However, predicting elongation rates is challenging due to the trade-off between capturing distal codon interactions and focusing on proximal codon effects at the A site. Approaches capturing distal codon interactions in the coding sequences (CDS) of mRNA fail to effectively differentiate critical regions (codons near the A site) due to insufficient effective mechanisms for focusing on these regions. Conversely, due to the limitations of models when handling long mRNA sequences, some methods simplify inputs by conditioning solely on proximal codons surrounding the A site, leading to the loss of important information from distal codons. To address this issue, we leverage Mamba's success in capturing long-range dependencies to enable the consideration of distant codons' impact on the A site. Additionally, we introduce a sliding window attention mechanism to emphasize the proximal codons around the A site during ribosome elongation. Building on these advancements, we present Sliding Window Attention Mamba (SWAMamba), a novel framework that simultaneously leverages both proximal and distal codon effects on the A site. We conduct comprehensive evaluations on ribosome data across four species and find that SWAMamba significantly outperformed current state-of-the-art methods in predicting translation elongation rates.

Designing novel biological sequences with desired properties is a significant challenge in biological science because of the extra large search space. The traditional design process usually involves multiple rounds of costly wet lab evaluations. To reduce the need for expensive wet lab experiments, machine learning methods are used to aid in designing biological sequences. However, the limited availability of biological sequences with known properties hinders the training of machine learning models, significantly restricting their applicability and performance. To fill this gap, we present ERLBioSeq, an Evolutionary Reinforcement Learning algorithm for BIOlogical SEQuence design. ERLBioSeq leverages the capability of reinforcement learning to learn without prior knowledge and the potential of evolutionary algorithms to enhance the exploration of reinforcement learning in the large search space of biological sequences. Additionally, to enhance the efficiency of biological sequence design, we developed a predictor for sequence screening in the biological sequence design process, which incorporates both the local and global sequence information. We evaluated the proposed method on three main types of biological sequence design tasks, including the design of DNA, RNA, and protein. The results demonstrate that the proposed method achieves significant improvement compared to the existing state-of-the-art methods.