Identifying cancer driver genes (CDGs) is essential for understanding cancer mechanisms and developing targeted therapies. Graph neural networks (GNNs) have recently been employed to identify CDGs by capturing patterns in biological interaction networks. However, most GNN-based approaches rely on a single protein-protein interaction (PPI) network, ignoring complementary information from other biological networks. Some studies integrate multiple networks by aligning features with consistency constraints to learn unified gene representations for CDG identification. However, such representation-level fusion often assumes congruent gene relationships across networks, which may overlook network heterogeneity and introduce conflicting information. To address this, we propose Soft-Evidence Fusion Graph Neural Network (SEFGNN), a novel framework for CDG identification across multiple networks at the decision level. Instead of enforcing feature-level consistency, SEFGNN treats each biological network as an independent evidence source and performs uncertainty-aware fusion at the decision level using Dempster-Shafer Theory (DST). To alleviate the risk of overconfidence from DST, we further introduce a Soft Evidence Smoothing (SES) module that improves ranking stability while preserving discriminative performance. Experiments on three cancer datasets show that SEFGNN consistently outperforms state-of-the-art baselines and exhibits strong potential in discovering novel CDGs.

The development of single-cell sequencing technology had promoted the generation of a large amount of single-cell transcriptional profiles, providing valuable opportunities to explore drug-resistant cell subpopulations in a tumor. However, the drug sensitivity data in single-cell level is still scarce to date, pressing an urgent and highly challenging task for computational prediction of the drug sensitivity to individual cells. This paper proposed scAdaDrug, a multi-source adaptive weighting model to predict single-cell drug sensitivity. We used an autoencoder to extract domain-invariant features related to drug sensitivity from multiple source domains by exploiting adversarial domain adaptation. Especially, we introduced an adaptive weight generator to produce importance-aware and mutual independent weights, which could adaptively modulate the embedding of each sample in dimension-level for both source and target domains. Extensive experimental results showed that our model achieved state-of-the-art performance in predicting drug sensitivity on sinle-cell datasets, as well as on cell line and patient datasets.

High-throughput screening technology has facilitated the generation of large-scale drug responses across hundreds of cancer cell lines. However, there exists significant discrepancy between in vitro cell lines and actual tumors in vivo in terms of their response to drug treatments, because of tumors comprise of complex cellular compositions and histopathology structure, known as tumor microenvironment (TME), which greatly influences the drug cytotoxicity against tumor cells. To date, no study has focused on modeling the impact of the TME on clinical drug response. This paper proposed a domain adaptation network for feature disentanglement to separate representations of cancer cells and TME of a tumor in patients. Two denoising autoencoders were separately used to extract features from cell lines (source domain) and tumors (target domain) for partial domain alignment and feature decoupling. The specific encoder was enforced to extract information only about TME. Moreover, to ensure generalizability to novel drugs, we applied a graph attention network to learn the latent representation of drugs, allowing us to linearly model the drug perturbation on cellular state in latent space. We calibrated our model on a benchmark dataset and demonstrated its superior performance in predicting clinical drug response and dissecting the influence of the TME on drug efficacy.

In line with recent advances in neural drug design 1.1 Motivation and sensitivity prediction, we propose a novel Discovery of novel compounds with a desired efficacy and architecture for interpretable prediction of anticancer improving existing therapies are key bottlenecks in the pharmaceutical compound sensitivity using a multimodal industry, which fuel the largest R&D business attention-based convolutional encoder. Our model spending of any industry and account for 19% of the total is based on the three key pillars of drug sensitivity: R&D spending worldwide (Petrova, 2014; Goh et al., compounds' structure in the form of a SMILES 2017). Anticancer compounds, in particular, take the lion's sequence, gene expression profiles of tumors and share of drug discovery R&D efforts, with over 34% of all prior knowledge on intracellular interactions from drugs in the global R&D pipeline in 2018 (5,212 of 15,267 protein-protein interaction networks. We demonstrate drugs) (Lloyd et al., 2017). Despite enormous scientific that our multiscale convolutional attentionbased and technological advances in recent years, serendipity still (MCA) encoder significantly outperforms a plays a major role in anticancer drug discovery (Hargrave-baseline model trained on Morgan fingerprints, a Thomas et al., 2012) without a systematic way to accumulate selection of encoders based on SMILES as well and leverage years of R&D to achieve higher success as previously reported state of the art for multimodal rates in drug discovery. On the other hand, there is strong drug sensitivity prediction (R2 0.86 evidence that the response to anticancer therapy is highly dependent and RMSE 0.89).

Predicting the response of cancer cells to drugs is an important problem in pharmacogenomics. Recent efforts in generation of large scale datasets profiling gene expression and drug sensitivity in cell lines have provided a unique opportunity to study this problem. However, one major challenge is the small number of samples (cell lines) compared to the number of features (genes) even in these large datasets. We propose a collaborative filtering (CF) like algorithm for modeling gene-drug relationship to identify patients most likely to benefit from a treatment. Due to the correlation of gene expressions in different cell lines, the gene expression matrix is approximately low-rank, which suggests that drug responses could be estimated from a reduced dimension latent space of the gene expression. Towards this end, we propose a joint low-rank matrix factorization and latent linear regression approach. Experiments with data from the Genomics of Drug Sensitivity in Cancer database are included to show that the proposed method can predict drug-gene associations better than the state-of-the-art methods.

We present the Network-based Biased Tree Ensembles (NetBiTE) method for drug sensitivity prediction and drug sensitivity biomarker identification in cancer using a combination of prior knowledge and gene expression data. Our devised method consists of a biased tree ensemble that is built according to a probabilistic bias weight distribution. The bias weight distribution is obtained from the assignment of high weights to the drug targets and propagating the assigned weights over a protein-protein interaction network such as STRING. The propagation of weights, defines neighborhoods of influence around the drug targets and as such simulates the spread of perturbations within the cell, following drug administration. Using a synthetic dataset, we showcase how application of biased tree ensembles (BiTE) results in significant accuracy gains at a much lower computational cost compared to the unbiased random forests (RF) algorithm. We then apply NetBiTE to the Genomics of Drug Sensitivity in Cancer (GDSC) dataset and demonstrate that NetBiTE outperforms RF in predicting IC50 drug sensitivity, only for drugs that target membrane receptor pathways (MRPs): RTK, EGFR and IGFR signaling pathways. We propose based on the NetBiTE results, that for drugs that inhibit MRPs, the expression of target genes prior to drug administration is a biomarker for IC50 drug sensitivity following drug administration. We further verify and reinforce this proposition through control studies on, PI3K/MTOR signaling pathway inhibitors, a drug category that does not target MRPs, and through assignment of dummy targets to MRP inhibiting drugs and investigating the variation in NetBiTE accuracy.

Selecting the right drugs for the right patients is a primary goal of precision medicine. In this manuscript, we consider the problem of cancer drug selection in a learning-to-rank framework. We have formulated the cancer drug selection problem as to accurately predicting 1). the ranking positions of sensitive drugs and 2). the ranking orders among sensitive drugs in cancer cell lines based on their responses to cancer drugs. We have developed a new learning-to-rank method, denoted as pLETORg , that predicts drug ranking structures in each cell line via using drug latent vectors and cell line latent vectors. The pLETORg method learns such latent vectors through explicitly enforcing that, in the drug ranking list of each cell line, the sensitive drugs are pushed above insensitive drugs, and meanwhile the ranking orders among sensitive drugs are correct. Genomics information on cell lines is leveraged in learning the latent vectors. Our experimental results on a benchmark cell line-drug response dataset demonstrate that the new pLETORg significantly outperforms the state-of-the-art method in prioritizing new sensitive drugs.

In this paper, we study the effects of different prior and likelihood choices for Bayesian matrix factorisation, focusing on small datasets. These choices can greatly influence the predictive performance of the methods. We identify four groups of approaches: Gaussian-likelihood with real-valued priors, nonnegative priors, semi-nonnegative models, and finally Poisson-likelihood approaches. For each group we review several models from the literature, considering sixteen in total, and discuss the relations between different priors and matrix norms. We extensively compare these methods on eight real-world datasets across three application areas, giving both inter- and intra-group comparisons. We measure convergence runtime speed, cross-validation performance, sparse and noisy prediction performance, and model selection robustness. We offer several insights into the trade-offs between prior and likelihood choices for Bayesian matrix factorisation on small datasets - such as that Poisson models give poor predictions, and that nonnegative models are more constrained than real-valued ones.

Accurately predicting drug responses to cancer is an important problem hindering oncologists' efforts to find the most effective drugs to treat cancer, which is a core goal in precision medicine. The scientific community has focused on improving this prediction based on genomic, epigenomic, and proteomic datasets measured in human cancer cell lines. Real-world cancer cell lines contain noise, which degrades the performance of machine learning algorithms. This problem is rarely addressed in the existing approaches. In this paper, we present a noise-filtering approach that integrates techniques from numerical linear algebra and information retrieval targeted at filtering out noisy cancer cell lines. By filtering out noisy cancer cell lines, we can train machine learning algorithms on better quality cancer cell lines. We evaluate the performance of our approach and compare it with an existing approach using the Area Under the ROC Curve (AUC) on clinical trial data. The experimental results show that our proposed approach is stable and also yields the highest AUC at a statistically significant level.