Drug repositioning, finding new indications for existing drugs, has gained much recent attention as a potentially efficient and economical strategy for accelerating new therapies into the clinic. Although improvement in the sensitivity of computational drug repositioning methods has identified numerous credible repositioning opportunities, few have been progressed. Arguably the “black box” nature of drug action in a new indication is one of the main blocks to progression, highlighting the need for methods that inform on the broader target mechanism in the disease context. We demonstrate that the analysis of co-expressed genes may be a critical first step towards illumination of both disease pathology and mode of drug action. We achieve this using a novel framework, co-expressed gene-set enrichment analysis (cogena) for co-expression analysis of gene expression signatures and gene set enrichment analysis of co-expressed genes. The cogena framework enables simultaneous, pathway driven, disease and drug repositioning analysis. Cogena can be used to illuminate coordinated changes within disease transcriptomes and identify drugs acting mechanistically within this framework. We illustrate this using a psoriatic skin transcriptome, as an exemplar, and recover two widely used Psoriasis drugs (Methotrexate and Ciclosporin) with distinct modes of action. Cogena out-performs the results of Connectivity Map and NFFinder webservers in similar disease transcriptome analyses. Furthermore, we investigated the literature support for the other top-ranked compounds to treat psoriasis and showed how the outputs of cogena analysis can contribute new insight to support the progression of drugs into the clinic. We have made cogena freely available within Bioconductor or https://github.com/zhilongjia/cogena . In conclusion, by targeting co-expressed genes within disease transcriptomes, cogena offers novel biological insight, which can be effectively harnessed for drug discovery and repositioning, allowing the grouping and prioritisation of drug repositioning candidates on the basis of putative mode of action.

Graph classification is a fundamental problem with diverse applications in bioinformatics and chemistry. Due to the intricate procedures of manual annotations in graphical domains, there may be abundant noisy labels of graphs in practice, resulting in poor performance for existing supervised methods. Thus, it is necessary and urgent to study the problem of graph classification with label noise. However, this problem is challenging due to the overfitting of noisy data as well as complicated relational structures of graphs. To handle this problem, we present a simple but effective approach called c O upled M ix for G raph Contrast (OMG), which combines coupled Mixup with graph contrastive learning in the feature space. On the one hand, to improve the model generalization, we take convex combination of sample pairs in the feature space for positive pair construction. On the other hand, to accomplish effective optimization, we offer challenging negatives by multiple sample Mixup with different emphasis. To further reduce the impact of noisy data, we develop a neighbour-aware noise removal strategy, which promotes the smoothness in the neighbourhood of samples following the principle of curriculum learning. Extensive experiments on a range of benchmark datasets demonstrate the superiority of our proposed OMG.

Anchor technology is popularly employed in multi-view subspace clustering (MVSC) to reduce the complexity cost. However, due to the sampling operation being performed on each individual view independently and not considering the distribution of samples in all views, the produced anchors are usually slightly distinguishable, failing to characterize the whole data. Moreover, it is necessary to fuse multiple separated graphs into one, which leads to the final clustering performance heavily subject to the fusion algorithm adopted. What is worse, existing MVSC methods generate dense bipartite graphs, where each sample is associated with all anchor candidates. We argue that this dense-connected mechanism will fail to capture the essential local structures and degrade the discrimination of samples belonging to the respective near anchor clusters. To alleviate these issues, we devise a clustering framework named SL-CAUBG. Specifically, we do not utilize sampling strategy but optimize to generate the consensus anchors within all views so as to explore the information between different views. Based on the consensus anchors, we skip the fusion stage and directly construct the unified bipartite graph across views. Most importantly, $\ell_1$ norm and Laplacian-rank constraints employed on the unified bipartite graph make it capture both local and global structures simultaneously. $\ell_1$ norm helps eliminate the scatters between anchors and samples by constructing sparse links and guarantees our graph to be with clear anchor-sample affinity relationship. Laplacian-rank helps extract the global characteristics by measuring the connectivity of unified bipartite graph. To deal with the nondifferentiable objective function caused by $\ell_1$ norm, we adopt an iterative re-weighted method and the Newton’s method. To handle the nonconvex Laplacian-rank, we equivalently transform it as a convex trace constraint. We also devise a four-step alternate method with linear complexity to solve the resultant problem. Substantial experiments show the superiority of our SL-CAUBG.

Tracking by detection has been the prevailing paradigm in the field of Multi-object Tracking (MOT). These methods typically rely on the Kalman Filter to estimate the future locations of objects, assuming linear object motion. However, they fall short when tracking objects exhibiting nonlinear and diverse motion in scenarios like dancing and sports. In addition, there has been limited focus on utilizing learning-based motion predictors in MOT. To address these challenges, we resort to exploring data-driven motion prediction methods. Inspired by the great expectation of state space models (SSMs), such as Mamba, in long-term sequence modeling with near-linear complexity, we introduce a Mamba-based motion model named Mamba moTion Predictor (MTP). MTP is designed to model the complex motion patterns of objects like dancers and athletes. Specifically, MTP takes the spatial-temporal location dynamics of objects as input, captures the motion pattern using a bi-Mamba encoding layer, and predicts the next motion. In real-world scenarios, objects may be missed due to occlusion or motion blur, leading to premature termination of their trajectories. To tackle this challenge, we further expand the application of MTP. We employ it in an autoregressive way to compensate for missing observations by utilizing its own predictions as inputs, thereby contributing to more consistent trajectories. Our proposed tracker, MambaTrack, demonstrates advanced performance on benchmarks such as Dancetrack and SportsMOT, which are characterized by complex motion and severe occlusion.