Biological knowledge graph-guided investigation of immune therapy response in cancer with graph neural network.

The determination of transcriptome profiles that mediate immune therapy in cancer remains a major clinical and biological challenge. Despite responses induced by immune-check points inhibitors (ICIs) in diverse tumor types and all the big breakthroughs in cancer immunotherapy, most patients with solid tumors do not respond to ICI therapies. It still remains a big challenge to predict the ICI treatment response. Here, we propose a framework with multiple prior knowledge networks guided for immune checkpoints inhibitors prediction-DeepOmix-ICI (or ICInet for short). ICInet can predict the immune therapy response by leveraging geometric deep learning and prior biological knowledge graphs of gene-gene interactions. Here, we demonstrate more than 600 ICI-treated patients with ICI response data and gene expression profile to apply on ICInet. ICInet was used for ICI therapy responses prediciton across different cancer types-melanoma, gastric cancer and bladder cancer, which includes 7 cohorts from different data sources. ICInet is able to robustly generalize into multiple cancer types. Moreover, the performance of ICInet in those cancer types can outperform other ICI biomarkers in the clinic. Our model [area under the curve (AUC = 0.85)] generally outperformed other measures, including tumor mutational burden (AUC = 0.62) and programmed cell death ligand-1 score (AUC = 0.74). Therefore, our study presents a prior-knowledge guided deep learning method to effectively select immunotherapy-response-associated biomarkers, thereby improving the prediction of immunotherapy response for precision oncology.

Multi-modality artificial intelligence in digital pathology.

In common medical procedures, the time-consuming and expensive nature of obtaining test results plagues doctors and patients. Digital pathology research allows using computational technologies to manage data, presenting an opportunity to improve the efficiency of diagnosis and treatment. Artificial intelligence (AI) has a great advantage in the data analytics phase. Extensive research has shown that AI algorithms can produce more up-to-date and standardized conclusions for whole slide images. In conjunction with the development of high-throughput sequencing technologies, algorithms can integrate and analyze data from multiple modalities to explore the correspondence between morphological features and gene expression. This review investigates using the most popular image data, hematoxylin-eosin stained tissue slide images, to find a strategic solution for the imbalance of healthcare resources. The article focuses on the role that the development of deep learning technology has in assisting doctors' work and discusses the opportunities and challenges of AI.

An effective self-supervised framework for learning expressive molecular global representations to drug discovery.

How to produce expressive molecular representations is a fundamental challenge in artificial intelligence-driven drug discovery. Graph neural network (GNN) has emerged as a powerful technique for modeling molecular data. However, previous supervised approaches usually suffer from the scarcity of labeled data and poor generalization capability. Here, we propose a novel molecular pre-training graph-based deep learning framework, named MPG, that learns molecular representations from large-scale unlabeled molecules. In MPG, we proposed a powerful GNN for modelling molecular graph named MolGNet, and designed an effective self-supervised strategy for pre-training the model at both the node and graph-level. After pre-training on 11 million unlabeled molecules, we revealed that MolGNet can capture valuable chemical insights to produce interpretable representation. The pre-trained MolGNet can be fine-tuned with just one additional output layer to create state-of-the-art models for a wide range of drug discovery tasks, including molecular properties prediction, drug-drug interaction and drug-target interaction, on 14 benchmark datasets. The pre-trained MolGNet in MPG has the potential to become an advanced molecular encoder in the drug discovery pipeline.

DeepFusion: A deep bimodal information fusion network for unraveling protein-RNA interactions using in vivo RNA structures.

RNA-binding proteins (RBPs) are key post-transcriptional regulators, and the malfunctions of RBP-RNA binding lead to diverse human diseases. However, prediction of RBP binding sites is largely based on RNA sequence features, whereas in vivo RNA structural features based on high-throughput sequencing are rarely incorporated. Here, we designed a deep bimodal information fusion network called DeepFusion for unraveling protein-RNA interactions by incorporating structural features derived from DMS-seq data. DeepFusion integrates two sub-models to extract local motif-like information and long-term context information. We show that DeepFusion performs best compared with other cutting-edge methods with only sequence inputs on two datasets. DeepFusion's performance is further improved with bimodal input after adding in vivo DMS-seq structural features. Furthermore, DeepFusion can be used for analyzing RNA degradation, demonstrating significantly different RBP-binding scores in genes with slow degradation rates versus those with rapid degradation rates. DeepFusion thus provides enhanced abilities for further analysis of functional RNAs. DeepFusion's code and data are available at http://bioinfo.org/deepfusion/.

Layered Metal Oxide Nanosheets with Enhanced Interlayer Space for Electrochemical Deionization.

Electrochemical deionization is regarded as one of the promising water treatment technologies. Here, CoAl-layered metal oxide nanosheets intercalated by sodium dodecyl sulfate (SDS) with an enhanced interlayer spacing from 0.76 to 1.33 nm are synthesized and used as an anode. The enlarged interlayer spacing provides an enhanced ion-diffusion channel and improves the utilization of the interlayer electroactive sites, while heat treatment, transferring layered double hydroxides to layered metal oxides (LMOs), offers additional active oxidation reaction sites to facilitate the electro-sorption rate, contributing to the high salt adsorption capacity (31.78 mg g-1 ) and average salt adsorption rate (3.75 mg g-1  min-1 ) at 1.2 V in 500 mg L-1 NaCl solution. In addition, the excellent long-term cycling stability (92.9%) after 40 cycles proves the strong electronic interaction between SDS and the host layer, which is validated by density functional theory calculations later on. Moreover, the electro-sorption mechanism of LMOs that originated from the reconstruction of the layered structure based on the "memory effect" is revealed according to the X-ray photoelectron spectroscopy peak shifts of Co element. This strategy of expanding the interlayer spacing combined with heat treatment makes LMOs a competitive candidate for electrochemical water deionization.