RESUMO
MOTIVATION: Accurately identifying the drug-target interactions (DTIs) is one of the crucial steps in the drug discovery and drug repositioning process. Currently, many computational-based models have already been proposed for DTI prediction and achieved some significant improvement. However, these approaches pay little attention to fuse the multi-view similarity networks related to drugs and targets in an appropriate way. Besides, how to fully incorporate the known interaction relationships to accurately represent drugs and targets is not well investigated. Therefore, there is still a need to improve the accuracy of DTI prediction models. RESULTS: In this study, we propose a novel approach that employs Multi-view similarity network fusion strategy and deep Interactive attention mechanism to predict Drug-Target Interactions (MIDTI). First, MIDTI constructs multi-view similarity networks of drugs and targets with their diverse information and integrates these similarity networks effectively in an unsupervised manner. Then, MIDTI obtains the embeddings of drugs and targets from multi-type networks simultaneously. After that, MIDTI adopts the deep interactive attention mechanism to further learn their discriminative embeddings comprehensively with the known DTI relationships. Finally, we feed the learned representations of drugs and targets to the multilayer perceptron model and predict the underlying interactions. Extensive results indicate that MIDTI significantly outperforms other baseline methods on the DTI prediction task. The results of the ablation experiments also confirm the effectiveness of the attention mechanism in the multi-view similarity network fusion strategy and the deep interactive attention mechanism. AVAILABILITY AND IMPLEMENTATION: https://github.com/XuLew/MIDTI.
Assuntos
Biologia Computacional , Biologia Computacional/métodos , Descoberta de Drogas/métodos , Algoritmos , Reposicionamento de Medicamentos/métodos , Preparações Farmacêuticas/metabolismo , Preparações Farmacêuticas/química , HumanosRESUMO
Identifying disease-associated microRNAs (miRNAs) could help understand the deep mechanism of diseases, which promotes the development of new medicine. Recently, network-based approaches have been widely proposed for inferring the potential associations between miRNAs and diseases. However, these approaches ignore the importance of different relations in meta-paths when learning the embeddings of miRNAs and diseases. Besides, they pay little attention to screening out reliable negative samples which is crucial for improving the prediction accuracy. In this study, we propose a novel approach named MGCNSS with the multi-layer graph convolution and high-quality negative sample selection strategy. Specifically, MGCNSS first constructs a comprehensive heterogeneous network by integrating miRNA and disease similarity networks coupled with their known association relationships. Then, we employ the multi-layer graph convolution to automatically capture the meta-path relations with different lengths in the heterogeneous network and learn the discriminative representations of miRNAs and diseases. After that, MGCNSS establishes a highly reliable negative sample set from the unlabeled sample set with the negative distance-based sample selection strategy. Finally, we train MGCNSS under an unsupervised learning manner and predict the potential associations between miRNAs and diseases. The experimental results fully demonstrate that MGCNSS outperforms all baseline methods on both balanced and imbalanced datasets. More importantly, we conduct case studies on colon neoplasms and esophageal neoplasms, further confirming the ability of MGCNSS to detect potential candidate miRNAs. The source code is publicly available on GitHub https://github.com/15136943622/MGCNSS/tree/master.
Assuntos
Neoplasias do Colo , MicroRNAs , Humanos , MicroRNAs/genética , Algoritmos , Biologia Computacional/métodos , Software , Neoplasias do Colo/genéticaRESUMO
Little is known about: (a) whether bilingual signers possess dissociated neural mechanisms for noun and verb processing in written language (just like native non-signers), or they utilize similar neural mechanisms for those processing (due to general lack of part-of-speech criterion in sign languages); and (b) whether learning a language from another modality (L2) influences corresponding neural mechanism of L1. In order to address these issues, we conducted an electroencephalogram (EEG) based reading comprehension study on bimodal bilinguals, namely Chinese native deaf signers, whose L1 is Chinese Sign Language and L2 is written Chinese. Analyses identified significantly dissociated neural mechanisms in the bilingual signers' written noun and verb processing (which also became more explicit along with increase in their written Chinese understanding levels), but not in their understanding of verbal and nominal meanings in Chinese Sign Language. These findings reveal relevance between modality-based linguistic features and processing mechanisms, which suggests that: processing modality-based features of a language is unlikely affected by learning another language in a different modality; and cross-modal language transfer is subject to modal constraints rather than explicit linguistic features.