Protein Function Prediction With Functional and Topological Knowledge of Gene Ontology.

Gene Ontology (GO) is a widely used bioinformatics resource for describing biological processes, molecular functions, and cellular components of proteins. It covers more than 5000 terms hierarchically organized into a directed acyclic graph and known functional annotations. Automatically annotating protein functions by using GO-based computational models has been an area of active research for a long time. However, due to the limited functional annotation information and complex topological structures of GO, existing models cannot effectively capture the knowledge representation of GO. To solve this issue, we present a method that fuses the functional and topological knowledge of GO to guide protein function prediction. This method employs a multi-view GCN model to extract a variety of GO representations from functional information, topological structure, and their combinations. To dynamically learn the significance weights of these representations, it adopts an attention mechanism to learn the final knowledge representation of GO. Furthermore, it uses a pre-trained language model (i.e., ESM-1b) to efficiently learn biological features for each protein sequence. Finally, it obtains all predicted scores by calculating the dot product of sequence features and GO representation. Our method outperforms other state-of-the-art methods, as demonstrated by the experimental results on datasets from three different species, namely Yeast, Human and Arabidopsis. Our proposed method's code can be accessed at: https://github.com/Candyperfect/Master.

Improving Protein Function Prediction by Adaptively Fusing Information From Protein Sequences and Biomedical Literature.

Proteins are the main undertakers of life activities, and accurately predicting their biological functions can help human better understand life mechanism and promote the development of themselves. With the rapid development of high-throughput technologies, an abundance of proteins are discovered. However, the gap between proteins and function annotations is still huge. To accelerate the process of protein function prediction, some computational methods taking advantage of multiple data have been proposed. Among these methods, the deep-learning-based methods are currently the most popular for their capability of learning information automatically from raw data. However, due to the diversity and scale difference between data, it is challenging for existing deep learning methods to capture related information from different data effectively. In this paper, we introduce a deep learning method that can adaptively learn information from protein sequences and biomedical literature, namely DeepAF. DeepAF first extracts the two kinds of information by using different extractors, which are built based on pre-trained language models and can capture rudimentary biological knowledge. Then, to integrate those information, it performs an adaptive fusion layer based on a Cross-attention mechanism that considers the knowledge of mutual interactions between two information. Finally, based on the mixed information, DeepAF utilizes logistic regression to obtain prediction scores. The experimental results on the datasets of two species (i.e., Human and Yeast) show that DeepAF outperforms other state-of-the-art approaches.

PINet 1.0: A pathway network-based evaluation of drug combinations for the management of specific diseases.

Drug combinations can increase the therapeutic effect by reducing the level of toxicity and the occurrence of drug resistance. Therefore, several drug combinations are often used in the management of complex diseases. However, due to the exponential growth in drug development, it would be impractical to evaluate all combinations through experiments. In view of this, we developed Pathway Interaction Network (PINet) biological model to estimate the optimal drug combinations for various diseases. The random walk with restart (RWR) algorithm was used to capture the "disease state" and "drug state," while PINet was used to evaluate the optimal drug combinations and the high-order drug combination. The model achieved a mean area under the curve of a receiver operating characteristic curve of 0.885. In addition, for some diseases, PINet predicted the optimal drug combination. For example, in the case of acute myeloid leukemia, PINet correctly predicted midostaurin and gemtuzumab as effective drug combinations, as demonstrated by the results of a Phase-I clinical trial. Moreover, PINet also correctly predicted the potential drug combinations for diseases that lacked a training dataset that could not be predicted using standard machine learning models.