In silico reuse of old drugs (also known as drug repositioning) to treat common and rare diseases is increasingly becoming an attractive proposition because it involves the use of de-risked drugs, with potentially lower overall development costs and shorter development timelines. Therefore, there is a pressing need for computational drug repurposing methodologies to facilitate drug discovery. In this study, we propose a new method, called DRHGCN (Drug Repositioning based on the Heterogeneous information fusion Graph Convolutional Network), to discover potential drugs for a certain disease. To make full use of different topology information in different domains (i.e. drug–drug similarity, disease–disease similarity and drug–disease association networks), we first design inter- and intra-domain feature extraction modules by applying graph convolution operations to the networks to learn the embedding of drugs and diseases, instead of simply integrating the three networks into a heterogeneous network. Afterwards, we parallelly fuse the inter- and intra-domain embeddings to obtain the more representative embeddings of drug and disease. Lastly, we introduce a layer attention mechanism to combine embeddings from multiple graph convolution layers for further improving the prediction performance. We find that DRHGCN achieves high performance (the average AUROC is 0.934 and the average AUPR is 0.539) in four benchmark datasets, outperforming the current approaches. Importantly, we conducted molecular docking experiments on DRHGCN-predicted candidate drugs, providing several novel approved drugs for Alzheimer’s disease (e.g. benzatropine) and Parkinson’s disease (e.g. trihexyphenidyl and haloperidol).
In recent years, miRNAs have been verified to play an irreplaceable role in biological processes associated with human disease. Discovering potential disease-related miRNAs helps explain the underlying pathogenesis of the disease at the molecular level. Given the high cost and labor intensity of biological experiments, computational predictions will be an indispensable alternative. Therefore, we design a new model called probability matrix factorization (PMFMDA). Specifically, we first integrate miRNA and disease similarity. Next, the known association matrix and integrated similarity matrix are utilized to construct a probability matrix factorization algorithm to identify potentially relevant miRNAs for disease. We find that PMFMDA achieves reliable performance in the frameworks of global leave-one-out cross validation (LOOCV) and 5-fold cross validation (AUCs are 0.9237 and 0.9187, respectively) in the HMDD (V2.0) dataset, significantly outperforming a few stateof-the-art methods including CMFMDA, IMCMDA, NCPMDA, RLSMDA, and RWRMDA. In addition, case studies show that PMFMDA has good predictive performance for new associations, and the evidence can be identified by literature mining.
Nowadays three-dimensional (3D) printing has been widely used for producing geometrically complex 3D structures from a broad range of materials such as ceramics, metals, polymers, semiconductors, etc. Although it has been demonstrated that a fabrication resolution as high as ~100 nm can be achieved in 3D printing based on two photon polymerization (TPP), the end product size of TPP is typically on millimeter scale limited by the short working distance of high-numerical-aperture focal lens. Here we present a method based on simultaneous spatiotemporal focusing (SSTF) of the femtosecond laser pulses that enables to fabricate centimeter-scale 3D structures of fine features with TPP. We also demonstrate an isotropic spatial resolution which can be continuously tuned in the range of ~10 μm and ~40 μm by only varying the power of femtosecond laser, making this technique extremely flexible and easy to implement. We fabricate several Chinese guardian lions of a maximum height of 0.6 cm and a Terra Cotta Warrior of a height of 1.3 cm using this method.
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