AbDPP: Target-oriented antibody design with pretraining and prior biological structure knowledge.

Antibodies represent a crucial class of complex protein therapeutics and are essential in the treatment of a wide range of human diseases. Traditional antibody discovery methods, such as hybridoma and phage display technologies, suffer from limitations including inefficiency and a restricted exploration of the immense space of potential antibodies. To overcome these limitations, we propose a novel method for generating antibody sequences using deep learning algorithms called AbDPP (target-oriented antibody design with pretraining and prior biological knowledge). AbDPP integrates a pretrained model for antibodies with biological region information, enabling the effective use of vast antibody sequence data and intricate biological system understanding to generate sequences. To target specific antigens, AbDPP incorporates an antibody property evaluation model, which is further optimized based on evaluation results to generate more focused sequences. The efficacy of AbDPP was assessed through multiple experiments, evaluating its ability to generate amino acids, improve neutralization and binding, maintain sequence consistency, and improve sequence diversity. Results demonstrated that AbDPP outperformed other methods in terms of the performance and quality of generated sequences, showcasing its potential to enhance antibody design and screening efficiency. In summary, this study contributes to the field by offering an innovative deep learning-based method for antibody generation, addressing some limitations of traditional approaches, and underscoring the importance of integrating a specific antibody pretrained model and the biological properties of antibodies in generating novel sequences. The code and documentation underlying this article are freely available at https://github.com/zlfyj/AbDPP.

Seq-RBPPred: Predicting RNA-Binding Proteins from Sequence.

RNA-binding proteins (RBPs) can interact with RNAs to regulate RNA translation, modification, splicing, and other important biological processes. The accurate identification of RBPs is of paramount importance for gaining insights into the intricate mechanisms underlying organismal life activities. Traditional experimental methods to predict RBPs require a lot of time and money, so it is important to develop computational methods to predict RBPs. However, the existing approaches for RBP prediction still require further improvement due to unidentified RBPs in many species. In this study, we present Seq-RBPPred (predicting RBPs from sequence), a novel method that utilizes a comprehensive feature representation encompassing both biophysical properties and hidden-state features derived from protein sequences. In the results, comprehensive performance evaluations of Seq-RBPPred its superiority compare with state-of-the-art methods, yielding impressive performance including 0.922 for overall accuracy, 0.926 for sensitivity, 0.903 for specificity, and Matthew's correlation coefficient (MCC) of 0.757 as ascertained from the evaluation of the testing set. The data and code of Seq-RBPPred are available at https://github.com/yaoyao-11/Seq-RBPPred.

The Interactome of Protein, DNA, and RNA.

Proteins participate in many processes of the organism and are very important for maintaining the health of the organism. However, proteins cannot function independently in the body. They must interact with proteins, DNA, RNA, and other substances to perform biological functions and maintain the body's health. At present, there are many experimental methods and software tools that can detect and predict the interaction between proteins and other substances. There are also many databases that record the interaction between proteins and other substances. This article mainly describes protein-protein, protein-DNA, and protein-RNA interactions in detail by introducing some commonly used experimental methods, the software tools produced with the accumulation of experimental data and the rapid development of machine learning, and the related databases that record the relationship between proteins and some substances. By this review, we hope that through the analysis and summary of various aspects, it will be convenient for researchers to conduct further research on protein interactions.

Generalized image outpainting with U-transformer.

In this paper, we develop a novel transformer-based generative adversarial neural network called U-Transformer for generalized image outpainting problems. Different from most present image outpainting methods conducting horizontal extrapolation, our generalized image outpainting could extrapolate visual context all-side around a given image with plausible structure and details even for complicated scenery, building, and art images. Specifically, we design a generator as an encoder-to-decoder structure embedded with the popular Swin Transformer blocks. As such, our novel neural network can better cope with image long-range dependencies which are crucially important for generalized image outpainting. We propose additionally a U-shaped structure and multi-view Temporal Spatial Predictor (TSP) module to reinforce image self-reconstruction as well as unknown-part prediction smoothly and realistically. By adjusting the predicting step in the TSP module in the testing stage, we can generate arbitrary outpainting size given the input sub-image. We experimentally demonstrate that our proposed method could produce visually appealing results for generalized image outpainting against the state-of-the-art image outpainting approaches.

Mind the Gap: Alleviating Local Imbalance for Unsupervised Cross-Modality Medical Image Segmentation.

Unsupervised cross-modality medical image adaptation aims to alleviate the severe domain gap between different imaging modalities without using the target domain label. A key in this campaign relies upon aligning the distributions of source and target domain. One common attempt is to enforce the global alignment between two domains, which, however, ignores the fatal local-imbalance domain gap problem, i.e., some local features with larger domain gap are harder to transfer. Recently, some methods conduct alignment focusing on local regions to improve the efficiency of model learning. While this operation may cause a deficiency of critical information from contexts. To tackle this limitation, we propose a novel strategy to alleviate the domain gap imbalance considering the characteristics of medical images, namely Global-Local Union Alignment. Specifically, a feature-disentanglement style-transfer module first synthesizes the target-like source images to reduce the global domain gap. Then, a local feature mask is integrated to reduce the 'inter-gap' for local features by prioritizing those discriminative features with larger domain gap. This combination of global and local alignment can precisely localize the crucial regions in segmentation target while preserving the overall semantic consistency. We conduct a series of experiments with two cross-modality adaptation tasks, i,e. cardiac substructure and abdominal multi-organ segmentation. Experimental results indicate that our method achieves state-of-the-art performance in both tasks.

Identification of potential necroinflammation-associated necroptosis-related biomarkers for delayed graft function and renal allograft failure: a machine learning-based exploration in the framework of predictive, preventive, and personalized medicine.

Delayed graft function (DGF) is one of the key post-operative challenges for a subset of kidney transplantation (KTx) patients. Graft survival is significantly lower in recipients who have experienced DGF than in those who have not. Assessing the risk of chronic graft injury, predicting graft rejection, providing personalized treatment, and improving graft survival are major strategies for predictive, preventive, and personalized medicine (PPPM/3PM) to promote the development of transplant medicine. However, since PPPM aims to accurately identify disease by integrating multiple omics, current methods to predict DGF and graft survival can still be improved. Renal ischemia/reperfusion injury (IRI) is a pathological process experienced by all KTx recipients that can result in varying occurrences of DGF, chronic rejection, and allograft failure depending on its severity. During this process, a necroinflammation-mediated necroptosis-dependent secondary wave of cell death significantly contributes to post-IRI tubular cell loss. In this article, we obtained the expression matrices and corresponding clinical data from the GEO database. Subsequently, nine differentially expressed necroinflammation-associated necroptosis-related genes (NiNRGs) were identified by correlation and differential expression analysis. The subtyping of post-KTx IRI samples relied on consensus clustering; the grouping of prognostic risks and the construction of predictive models for DGF (the area under the receiver operating characteristic curve (AUC) of the internal validation set and the external validation set were 0.730 and 0.773, respectively) and expected graft survival after a biopsy (the internal validation set's 1-year AUC: 0.770; 2-year AUC: 0.702; and 3-year AUC: 0.735) were based on the least absolute shrinkage and selection operator regression algorithms. The results of the immune infiltration analysis showed a higher infiltration abundance of myeloid immune cells, especially neutrophils, macrophages, and dendritic cells, in the cluster A subtype and prognostic high-risk groups. Therefore, in the framework of PPPM, this work provides a comprehensive exploration of the early expression landscape, related pathways, immune features, and prognostic impact of NiNRGs in post-KTx patients and assesses their capabilities as.predictors of post-KTx DGF and graft loss,targets of the vicious loop between regulated tubular cell necrosis and necroinflammation for targeted secondary and tertiary prevention, andreferences for personalized immunotherapy. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-023-00320-w.