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Published on: August 17, 2019
NanoBeacon.AI: AI-Enhanced Nanodiamond Biosensor for Automated Sensitivity Prediction to Oxidative Phosphorylation
Jingru Xu1,2,3, Mengjia Zheng4, Dexter Kai Hao Thng1
1Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore.
Abstract:
Spalt-like transcription factor 4 (SALL4) is an oncofetal protein that has been identified to drive cancer progression in hepatocellular carcinoma (HCC) and hematological malignancies. Furthermore, a high SALL4 expression level is correlated to poor prognosis in these cancers. However, SALL4 lacks well-structured small-molecule binding pockets, making it difficult to design targeted inhibitors. SALL4-induced expression of oxidative phosphorylation (OXPHOS) genes may serve as a therapeutically targetable vulnerability in HCC through OXPHOS inhibition. Because OXPHOS functions through a set of genes with intertumoral heterogeneous expression, identifying therapeutic sensitivity to OXPHOS inhibitors may not rely on a single clear biomarker. Here, we developed a workflow that utilized molecular beacons, nucleic-acid-based, activatable sensors with high specificity to the target mRNA, delivered by nanodiamonds, to establish an artificial intelligence (AI)-assisted platform for rapid evaluation of patient-specific drug sensitivity. Specifically, when the HCC cells were treated with the nanodiamond-medicated OXPHOS biosensor, high sensitivity and specificity of the sensor allowed for improved identification of OXPHOS expression in cells. Assisted by a trained convolutional neural network, drug sensitivity of cells toward an OXPHOS inhibitor, IACS-010759, could be accurately predicted. AI-assisted OXPHOS drug sensitivity assessment could be accomplished within 1 day, enabling rapid and efficient clinical decision support for HCC treatment. The work proposed here serves as a foundation for the patient-based subtype-specific therapeutic research platform and is well suited for precision medicine.
Insights
This study introduces an AI-powered platform using nanodiamond-delivered biosensors to rapidly assess patient-specific drug sensitivity for hepatocellular carcinoma (HCC) by targeting oxidative phosphorylation (OXPHOS) gene expression.
Area of Science:
- Oncology
- Biotechnology
- Artificial Intelligence
Background:
- Spalt-like transcription factor 4 (SALL4) drives cancer progression in hepatocellular carcinoma (HCC) and hematological malignancies, correlating with poor prognosis.
- Targeting SALL4 is challenging due to its lack of well-defined binding pockets, but SALL4-induced oxidative phosphorylation (OXPHOS) gene expression presents a potential therapeutic vulnerability.
- Intertumoral heterogeneity in OXPHOS gene expression complicates identifying patients sensitive to OXPHOS inhibitors using single biomarkers.
Purpose of the Study:
- To develop a rapid, patient-specific drug sensitivity evaluation platform for HCC.
- To utilize molecular beacons and artificial intelligence (AI) for assessing OXPHOS expression and predicting sensitivity to OXPHOS inhibitors.
- To enable precision medicine by supporting patient-based, subtype-specific therapeutic decisions.
Main Methods:
- Development of a workflow utilizing molecular beacons, nucleic-acid-based sensors, delivered by nanodiamonds.
- Creation of an AI-assisted platform for rapid evaluation of patient-specific drug sensitivity.
- Employing a trained convolutional neural network for accurate prediction of drug sensitivity towards the OXPHOS inhibitor IACS-010759.
Main Results:
- Nanodiamond-mediated OXPHOS biosensors demonstrated high sensitivity and specificity in identifying OXPHOS expression in HCC cells.
- The AI-assisted platform accurately predicted patient-specific drug sensitivity to the OXPHOS inhibitor IACS-010759.
- Drug sensitivity assessment was achieved within one day, enabling rapid clinical decision support.
Conclusions:
- The developed AI-assisted platform offers a rapid and efficient method for evaluating OXPHOS-targeted drug sensitivity in HCC.
- This approach facilitates precision medicine by enabling patient-based, subtype-specific therapeutic strategies.
- The platform serves as a foundation for future research in personalized cancer treatment.
