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Motivation Accurate prediction of acute dermal toxicity (ADT) is essential for the safe and effective development of contact drugs. Currently, graph neural networks, a form of deep learning technology, accurately model the structure of compound molecules, enhancing predictions of their ADT. However, many existing methods emphasize atom-level information transfer and overlook crucial data conveyed by molecular bonds and their interrelationships. Additionally, these methods often generate "equal" node representations across the entire graph, failing to accentuate "important" substructures like functional groups, pharmacophores, and toxicophores, thereby reducing interpretability. Results We introduce a novel model, GraphADT, utilizing structure remapping and multi-view graph pooling (MVPool) technologies to accurately predict compound ADT. Initially, our model applies structure remapping to better delineate bonds, transforming "bonds" into new nodes and "bond-atom-bond" interactions into new edges, thereby reconstructing the compound molecular graph. Subsequently, we use MVPool to amalgamate data from various perspectives, minimizing biases inherent to single-view analyses. Following this, the model generates a robust node ranking collaboratively, emphasizing critical nodes or substructures to enhance model interpretability. Lastly, we apply a graph comparison learning strategy to train both the original and structure remapped molecular graphs, deriving the final molecular representation. Experimental results on public datasets indicate that the GraphADT model outperforms existing state-of-the-art models. The GraphADT model has been demonstrated to effectively predict compound ADT, offering potential guidance for the development of contact drugs and related treatments. Availability and implementation Our code and data are accessible at: https://github.com/mxqmxqmxq/GraphADT.git. [ABSTRACT FROM AUTHOR]

Motivation Peptides are promising agents for the treatment of a variety of diseases due to their specificity and efficacy. However, the development of peptide-based drugs is often hindered by the potential toxicity of peptides, which poses a significant barrier to their clinical application. Traditional experimental methods for evaluating peptide toxicity are time-consuming and costly, making the development process inefficient. Therefore, there is an urgent need for computational tools specifically designed to predict peptide toxicity accurately and rapidly, facilitating the identification of safe peptide candidates for drug development. Results We provide here a novel computational approach, CAPTP, which leverages the power of convolutional and self-attention to enhance the prediction of peptide toxicity from amino acid sequences. CAPTP demonstrates outstanding performance, achieving a Matthews correlation coefficient of approximately 0.82 in both cross-validation settings and on independent test datasets. This performance surpasses that of existing state-of-the-art peptide toxicity predictors. Importantly, CAPTP maintains its robustness and generalizability even when dealing with data imbalances. Further analysis by CAPTP reveals that certain sequential patterns, particularly in the head and central regions of peptides, are crucial in determining their toxicity. This insight can significantly inform and guide the design of safer peptide drugs. Availability and implementation The source code for CAPTP is freely available at https://github.com/jiaoshihu/CAPTP. [ABSTRACT FROM AUTHOR]

Motivation Continuous advancements in single-cell RNA sequencing (scRNA-seq) technology have enabled researchers to further explore the study of cell heterogeneity, trajectory inference, identification of rare cell types, and neurology. Accurate scRNA-seq data clustering is crucial in single-cell sequencing data analysis. However, the high dimensionality, sparsity, and presence of "false" zero values in the data can pose challenges to clustering. Furthermore, current unsupervised clustering algorithms have not effectively leveraged prior biological knowledge, making cell clustering even more challenging. Results This study investigates a semisupervised clustering model called scTPC, which integrates the t riplet constraint, p airwise constraint, and c ross-entropy constraint based on deep learning. Specifically, the model begins by pretraining a denoising autoencoder based on a zero-inflated negative binomial distribution. Deep clustering is then performed in the learned latent feature space using triplet constraints and pairwise constraints generated from partial labeled cells. Finally, to address imbalanced cell-type datasets, a weighted cross-entropy loss is introduced to optimize the model. A series of experimental results on 10 real scRNA-seq datasets and five simulated datasets demonstrate that scTPC achieves accurate clustering with a well-designed framework. Availability and implementation scTPC is a Python-based algorithm, and the code is available from https://github.com/LF-Yang/Code or https://zenodo.org/records/10951780. [ABSTRACT FROM AUTHOR]

Motivation Accurate inference of potential drug–protein interactions (DPIs) aids in understanding drug mechanisms and developing novel treatments. Existing deep learning models, however, struggle with accurate node representation in DPI prediction, limiting their performance. Results We propose a new computational framework that integrates global and local features of nodes in the drug–protein bipartite graph for efficient DPI inference. Initially, we employ pre-trained models to acquire fundamental knowledge of drugs and proteins and to determine their initial features. Subsequently, the MinHash and HyperLogLog algorithms are utilized to estimate the similarity and set cardinality between drug and protein subgraphs, serving as their local features. Then, an energy-constrained diffusion mechanism is integrated into the transformer architecture, capturing interdependencies between nodes in the drug–protein bipartite graph and extracting their global features. Finally, we fuse the local and global features of nodes and employ multilayer perceptrons to predict the likelihood of potential DPIs. A comprehensive and precise node representation guarantees efficient prediction of unknown DPIs by the model. Various experiments validate the accuracy and reliability of our model, with molecular docking results revealing its capability to identify potential DPIs not present in existing databases. This approach is expected to offer valuable insights for furthering drug repurposing and personalized medicine research. Availability and implementation Our code and data are accessible at: https://github.com/ZZCrazy00/DPI. [ABSTRACT FROM AUTHOR]

Motivation In bioinformatics, multiple sequence alignment (MSA) is a crucial task. However, conventional methods often struggle with aligning ultralong sequences. To address this issue, researchers have designed MSA methods rooted in a vertical division strategy, which segments sequence data for parallel alignment. A prime example of this approach is FMAlign, which utilizes the FM-index to extract common seeds and segment the sequences accordingly. Results FMAlign2 leverages the suffix array to identify maximal exact matches, redefining the approach of FMAlign from searching for global chains to partial chains. By using a vertical division strategy, large-scale problem is deconstructed into manageable tasks, enabling parallel execution of subMSA. Furthermore, sequence-profile alignment and refinement are incorporated to concatenate subsets, yielding the final result seamlessly. Compared to FMAlign, FMAlign2 markedly augments the segmentation of sequences and significantly reduces the time while maintaining accuracy, especially on ultralong datasets. Importantly, FMAlign2 enhances existing MSA methods by conferring the capability to handle sequences reaching billions in length within an acceptable time frame. Availability and implementation Source code and datasets are available at https://github.com/malabz/FMAlign2 and https://zenodo.org/records/10435770. [ABSTRACT FROM AUTHOR]