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Register a new userMolDesigner: Interactive Design of Efficacious Drugs with Deep Learning
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The efficacy of a drug depends on its binding affinity to the therapeutic target and pharmacokinetics. Deep learning (DL) has demonstrated remarkable progress in predicting drug efficacy. We develop MolDesigner, a human-in-the-loop web user-interface (UI), to assist drug developers leverage DL predictions to design more effective drugs. A developer can draw a drug molecule in the interface. In the backend, more than 17 state-of-the-art DL models generate predictions on important indices that are crucial for a drugs efficacy. Based on these predictions, drug developers can edit the drug molecule and reiterate until satisfaction. MolDesigner can make predictions in real-time with a latency of less than a second.
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Recent development of quantitative myocardial blood flow (MBF) mapping allows direct evaluation of absolute myocardial perfusion, by computing pixel-wise flow maps. Clinical studies suggest quantitative evaluation would be more desirable for objectivity and efficiency. Objective assessment can be further facilitated by segmenting the myocardium and automatically generating reports following the AHA model. This will free user interaction for analysis and lead to a one-click solution to improve workflow. This paper proposes a deep neural network based computational workflow for inline myocardial perfusion analysis. Adenosine stress and rest perfusion scans were acquired from three hospitals. Training set included N=1,825 perfusion series from 1,034 patients. Independent test set included 200 scans from 105 patients. Data were consecutively acquired at each site. A convolution neural net (CNN) model was trained to provide segmentation for LV cavity, myocardium and right ventricular by processing incoming 2D+T perfusion Gd series. Model outputs were compared to manual ground-truth for accuracy of segmentation and flow measures derived on global and per-sector basis. The trained models were integrated onto MR scanners for effective inference. Segmentation accuracy and myocardial flow measures were compared between CNN models and manual ground-truth. The mean Dice ratio of CNN derived myocardium was 0.93 +/- 0.04. Both global flow and per-sector values showed no significant difference, compared to manual results. The AHA 16 segment model was automatically generated and reported on the MR scanner. As a result, the fully automated analysis of perfusion flow mapping was achieved. This solution was integrated on the MR scanner, enabling one-click analysis and reporting of myocardial blood flow.
Intercellular heterogeneity is a major obstacle to successful personalized medicine. Single-cell RNA sequencing (scRNA-seq) technology has enabled in-depth analysis of intercellular heterogeneity in various diseases. However, its full potentials for personalized medicine are yet to be reached. Towards this, we propose A Single-cell Guided pipeline to Aid Repurposing of Drugs (ASGARD). ASGARD can repurpose single drugs for each cell cluster and for multiple cell clusters at individual patient levels; it can also predict personalized drug combinations to address the intercellular heterogeneity within each patient. We tested ASGARD on three independent datasets, including advanced metastatic breast cancer, acute lymphoblastic leukemia, and coronavirus disease 2019 (COVID-19). On single-drug therapy, ASGARD shows significantly better average accuracy (AUC=0.95) compared to two other single-cell pipelines (AUC 0.69 and 0.57) and two other bulk-cell-based drug repurposing methods (AUC 0.80 and 0.75). The top-ranked drugs, such as fulvestrant and neratinib for breast cancer, tretinoin and vorinostat for leukemia, and chloroquine and enalapril for severe COVID19, are either approved by FDA or in clinical trials treating corresponding diseases. In conclusion, ASGARD is a promising pipeline guided by single-cell RNA-seq data, for repurposing personalized drugs and drug combinations. ASGARD is free for academic use at https://github.com/lanagarmire/ASGARD.
COVID-19 clinical presentation and prognosis are highly variable, ranging from asymptomatic and paucisymptomatic cases to acute respiratory distress syndrome and multi-organ involvement. We developed a hybrid machine learning/deep learning model to classify patients in two outcome categories, non-ICU and ICU (intensive care admission or death), using 558 patients admitted in a northern Italy hospital in February/May of 2020. A fully 3D patient-level CNN classifier on baseline CT images is used as feature extractor. Features extracted, alongside with laboratory and clinical data, are fed for selection in a Boruta algorithm with SHAP game theoretical values. A classifier is built on the reduced feature space using CatBoost gradient boosting algorithm and reaching a probabilistic AUC of 0.949 on holdout test set. The model aims to provide clinical decision support to medical doctors, with the probability score of belonging to an outcome class and with case-based SHAP interpretation of features importance.
This paper presents a method to identify substructures in NMR spectra of mixtures, specifically 2D spectra, using a bespoke image-based Convolutional Neural Network application. This is done using HSQC and HMBC spectra separately and in combination. The application can reliably detect substructures in pure compounds, using a simple network. It can work for mixtures when trained on pure compounds only. HMBC data and the combination of HMBC and HSQC show better results than HSQC alone.
Current neuroimaging techniques provide paths to investigate the structure and function of the brain in vivo and have made great advances in understanding Alzheimers disease (AD). However, the group-level analyses prevalently used for investigation and understanding of the disease are not applicable for diagnosis of individuals. More recently, deep learning, which can efficiently analyze large-scale complex patterns in 3D brain images, has helped pave the way for computer-aided individual diagnosis by providing accurate and automated disease classification. Great progress has been made in classifying AD with deep learning models developed upon increasingly available structural MRI data. The lack of scale-matched functional neuroimaging data prevents such models from being further improved by observing functional changes in pathophysiology. Here we propose a potential solution by first learning a structural-to-functional transformation in brain MRI, and further synthesizing spatially matched functional images from large-scale structural scans. We evaluated our approach by building computational models to discriminate patients with AD from healthy normal subjects and demonstrated a performance boost after combining the structural and synthesized functional brain images into the same model. Furthermore, our regional analyses identified the temporal lobe to be the most predictive structural-region and the parieto-occipital lobe to be the most predictive functional-region of our model, which are both in concordance with previous group-level neuroimaging findings. Together, we demonstrate the potential of deep learning with large-scale structural and synthesized functional MRI to impact AD classification and to identify ADs neuroimaging signatures.
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