Dataset Information

Artificial intelligence-based computational framework for drug-target prioritization and inference of novel repositionable drugs for Alzheimer's disease.

ABSTRACT:

Background

Identifying novel therapeutic targets is crucial for the successful development of drugs. However, the cost to experimentally identify therapeutic targets is huge and only approximately 400 genes are targets for FDA-approved drugs. As a result, it is inevitable to develop powerful computational tools that can identify potential novel therapeutic targets. Fortunately, the human protein-protein interaction network (PIN) could be a useful resource to achieve this objective.

Methods

In this study, we developed a deep learning-based computational framework that extracts low-dimensional representations of high-dimensional PIN data. Our computational framework uses latent features and state-of-the-art machine learning techniques to infer potential drug target genes.

Results

We applied our computational framework to prioritize novel putative target genes for Alzheimer's disease and successfully identified key genes that may serve as novel therapeutic targets (e.g., DLG4, EGFR, RAC1, SYK, PTK2B, SOCS1). Furthermore, based on these putative targets, we could infer repositionable candidate-compounds for the disease (e.g., tamoxifen, bosutinib, and dasatinib).

Conclusions

Our deep learning-based computational framework could be a powerful tool to efficiently prioritize new therapeutic targets and enhance the drug repositioning strategy.

SUBMITTER: Tsuji S

PROVIDER: S-EPMC8091739 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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Publications

Artificial intelligence-based computational framework for drug-target prioritization and inference of novel repositionable drugs for Alzheimer's disease.

Tsuji Shingo S Hase Takeshi T Yachie-Kinoshita Ayako A Nishino Taiko T Ghosh Samik S Kikuchi Masataka M Shimokawa Kazuro K Aburatani Hiroyuki H Kitano Hiroaki H Tanaka Hiroshi H

Alzheimer's research & therapy 20210503 1

<h4>Background</h4>Identifying novel therapeutic targets is crucial for the successful development of drugs. However, the cost to experimentally identify therapeutic targets is huge and only approximately 400 genes are targets for FDA-approved drugs. As a result, it is inevitable to develop powerful computational tools that can identify potential novel therapeutic targets. Fortunately, the human protein-protein interaction network (PIN) could be a useful resource to achieve this objective.<h4>Me ...[more]

PMID: 33941241

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Project description:Aptamers are short single-stranded DNA, RNA, or synthetic Xeno nucleic acids (XNA) molecules that can interact with corresponding targets with high affinity. Owing to their unique features, including low cost of production, easy chemical modification, high thermal stability, reproducibility, as well as low levels of immunogenicity and toxicity, aptamers can be used as an alternative to antibodies in diagnostics and therapeutics. Systematic evolution of ligands by exponential enrichment (SELEX), an experimental approach for aptamer screening, allows the selection and identification of in vitro aptamers with high affinity and specificity. However, the SELEX process is time consuming and characterization of the representative aptamer candidates from SELEX is rather laborious. Artificial intelligence (AI) could help to rapidly identify the potential aptamer candidates from a vast number of sequences. This review discusses the advancements of AI pipelines/methods, including structure-based and machine/deep learning-based methods, for predicting the binding ability of aptamers to targets. Structure-based methods are the most used in computer-aided drug design. For this part, we review the secondary and tertiary structure prediction methods for aptamers, molecular docking, as well as molecular dynamic simulation methods for aptamer-target binding. We also performed analysis to compare the accuracy of different secondary and tertiary structure prediction methods for aptamers. On the other hand, advanced machine-/deep-learning models have witnessed successes in predicting the binding abilities between targets and ligands in drug discovery and thus potentially offer a robust and accurate approach to predict the binding between aptamers and targets. The research utilizing machine-/deep-learning techniques for prediction of aptamer-target binding is limited currently. Therefore, perspectives for models, algorithms, and implementation strategies of machine/deep learning-based methods are discussed. This review could facilitate the development and application of high-throughput and less laborious in silico methods in aptamer selection and characterization.

Project description:BackgroundThe aim of this study was to develop artificial intelligence (AI) guided framework to recognize tooth numbers in panoramic and intraoral radiographs (periapical and bitewing) without prior domain knowledge and arrange the intraoral radiographs into a full mouth series (FMS) arrangement template. This model can be integrated with different diseases diagnosis models, such as periodontitis or caries, to facilitate clinical examinations and diagnoses.MethodsThe framework utilized image segmentation models to generate the masks of bone area, tooth, and cementoenamel junction (CEJ) lines from intraoral radiographs. These masks were used to detect and extract teeth bounding boxes utilizing several image analysis methods. Then, individual teeth were matched with a patient's panoramic images (if available) or tooth repositories for assigning tooth numbers using the multi-scale matching strategy. This framework was tested on 1240 intraoral radiographs different from the training and internal validation cohort to avoid data snooping. Besides, a web interface was designed to generate a report for different dental abnormalities with tooth numbers to evaluate this framework's practicality in clinical settings.ResultsThe proposed method achieved the following precision and recall via panoramic view: 0.96 and 0.96 (via panoramic view) and 0.87 and 0.87 (via repository match) by handling tooth shape variation and outperforming other state-of-the-art methods. Additionally, the proposed framework could accurately arrange a set of intraoral radiographs into an FMS arrangement template based on positions and tooth numbers with an accuracy of 95% for periapical images and 90% for bitewing images. The accuracy of this framework was also 94% in the images with missing teeth and 89% with restorations.ConclusionsThe proposed tooth numbering model is robust and self-contained and can also be integrated with other dental diagnosis modules, such as alveolar bone assessment and caries detection. This artificial intelligence-based tooth detection and tooth number assignment in dental radiographs will help dentists with enhanced communication, documentation, and treatment planning accurately. In addition, the proposed framework can correctly specify detailed diagnostic information associated with a single tooth without human intervention.

Dataset Information

Artificial intelligence-based computational framework for drug-target prioritization and inference of novel repositionable drugs for Alzheimer's disease.

Background

Methods

Results

Conclusions

Publications

Artificial intelligence-based computational framework for drug-target prioritization and inference of novel repositionable drugs for Alzheimer's disease.

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