Dataset Information

Mitigating cold-start problems in drug-target affinity prediction with interaction knowledge transferring.

ABSTRACT: Predicting the drug-target interaction is crucial for drug discovery as well as drug repurposing. Machine learning is commonly used in drug-target affinity (DTA) problem. However, the machine learning model faces the cold-start problem where the model performance drops when predicting the interaction of a novel drug or target. Previous works try to solve the cold start problem by learning the drug or target representation using unsupervised learning. While the drug or target representation can be learned in an unsupervised manner, it still lacks the interaction information, which is critical in drug-target interaction. To incorporate the interaction information into the drug and protein interaction, we proposed using transfer learning from chemical-chemical interaction (CCI) and protein-protein interaction (PPI) task to drug-target interaction task. The representation learned by CCI and PPI tasks can be transferred smoothly to the DTA task due to the similar nature of the tasks. The result on the DTA datasets shows that our proposed method has advantages compared to other pre-training methods in the DTA task.

SUBMITTER: Nguyen TM

PROVIDER: S-EPMC9353967 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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Mitigating cold-start problems in drug-target affinity prediction with interaction knowledge transferring.

Nguyen Tri Minh TM Nguyen Thin T Tran Truyen T

Briefings in bioinformatics 20220701 4

Predicting the drug-target interaction is crucial for drug discovery as well as drug repurposing. Machine learning is commonly used in drug-target affinity (DTA) problem. However, the machine learning model faces the cold-start problem where the model performance drops when predicting the interaction of a novel drug or target. Previous works try to solve the cold start problem by learning the drug or target representation using unsupervised learning. While the drug or target representation can b ...[more]

PMID: 35788823

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Project description:BackgroundThe pharmaceutical field faces a significant challenge in validating drug target interactions (DTIs) due to the time and cost involved, leading to only a fraction being experimentally verified. To expedite drug discovery, accurate computational methods are essential for predicting potential interactions. Recently, machine learning techniques, particularly graph-based methods, have gained prominence. These methods utilize networks of drugs and targets, employing knowledge graph embedding (KGE) to represent structured information from knowledge graphs in a continuous vector space. This phenomenon highlights the growing inclination to utilize graph topologies as a means to improve the precision of predicting DTIs, hence addressing the pressing requirement for effective computational methodologies in the field of drug discovery.ResultsThe present study presents a novel approach called DTIOG for the prediction of DTIs. The methodology employed in this study involves the utilization of a KGE strategy, together with the incorporation of contextual information obtained from protein sequences. More specifically, the study makes use of Protein Bidirectional Encoder Representations from Transformers (ProtBERT) for this purpose. DTIOG utilizes a two-step process to compute embedding vectors using KGE techniques. Additionally, it employs ProtBERT to determine target-target similarity. Different similarity measures, such as Cosine similarity or Euclidean distance, are utilized in the prediction procedure. In addition to the contextual embedding, the proposed unique approach incorporates local representations obtained from the Simplified Molecular Input Line Entry Specification (SMILES) of drugs and the amino acid sequences of protein targets.ConclusionsThe effectiveness of the proposed approach was assessed through extensive experimentation on datasets pertaining to Enzymes, Ion Channels, and G-protein-coupled Receptors. The remarkable efficacy of DTIOG was showcased through the utilization of diverse similarity measures in order to calculate the similarities between drugs and targets. The combination of these factors, along with the incorporation of various classifiers, enabled the model to outperform existing algorithms in its ability to predict DTIs. The consistent observation of this advantage across all datasets underlines the robustness and accuracy of DTIOG in the domain of DTIs. Additionally, our case study suggests that the DTIOG can serve as a valuable tool for discovering new DTIs.

Project description:Background Several computational advances have been achieved in the drug discovery field, promoting the identification of novel drug–target interactions and new leads. However, most of these methodologies have been overlooking the importance of providing explanations to the decision-making process of deep learning architectures. In this research study, we explore the reliability of convolutional neural networks (CNNs) at identifying relevant regions for binding, specifically binding sites and motifs, and the significance of the deep representations extracted by providing explanations to the model’s decisions based on the identification of the input regions that contributed the most to the prediction. We make use of an end-to-end deep learning architecture to predict binding affinity, where CNNs are exploited in their capacity to automatically identify and extract discriminating deep representations from 1D sequential and structural data. Results The results demonstrate the effectiveness of the deep representations extracted from CNNs in the prediction of drug–target interactions. CNNs were found to identify and extract features from regions relevant for the interaction, where the weight associated with these spots was in the range of those with the highest positive influence given by the CNNs in the prediction. The end-to-end deep learning model achieved the highest performance both in the prediction of the binding affinity and on the ability to correctly distinguish the interaction strength rank order when compared to baseline approaches. Conclusions This research study validates the potential applicability of an end-to-end deep learning architecture in the context of drug discovery beyond the confined space of proteins and ligands with determined 3D structure. Furthermore, it shows the reliability of the deep representations extracted from the CNNs by providing explainability to the decision-making process. Supplementary Information The online version contains supplementary material available at 10.1186/s12859-022-04767-y.

Dataset Information

Mitigating cold-start problems in drug-target affinity prediction with interaction knowledge transferring.

Publications

Mitigating cold-start problems in drug-target affinity prediction with interaction knowledge transferring.

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