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Abstract Worldwide, governments imposed non-pharmaceutical interventions (NPIs) during the COVID-19 pandemic to contain the pandemic more effectively. We examined the effectiveness of individual NPIs in the United States during the first wave of the pandemic. Three types of analyses were performed. First, a prototypical Bayesian hierarchical model was employed to gauge the effectiveness of five NPIs and they are gathering restriction, restaurant capacity restriction, business closure, school closure, and stay-at-home order in the 42 states with over 100 deaths by the end of the wave. Second, we examined the effectiveness of the face mask mandate, the sixth and most controversial NPI by counterfactual modeling, which is a variant of the prototypical Bayesian hierarchical model allowing us to answer the question of what if the state had imposed the mandate or not. The third analysis used an advanced Bayesian hierarchical model to evaluate the effectiveness of all six NPIs in all 50 states and the District of Columbia, and thereby provide a full-scale estimation of the effectiveness of NPIs and the relative effectiveness of each NPI in the entire United States. Our results have enhanced the collective knowledge on the general effectiveness of NPIs in arresting the spread of COVID-19. 

Crossover designs play an increasingly important role in precision medicine. We show the search of an optimal crossover design can be formulated as a convex optimization problem and convex optimization tools, such as CVX, can be directly used to search for an optimal crossover design.  We first demonstrate how to transform crossover design problems into convex optimization problems and show CVX can effortlessly find optimal crossover designs that coincide with a few theoretical crossover optimal designs in the literature. The proposed approach is especially useful when it becomes problematic to construct optimal designs analytically for complicated models. We then apply CVX to find crossover designs for models with auto-correlated error structures or when the information matrices may be singular and analytical answers are unavailable. We also construct N-of-1 trials frequently used in precision medicine to estimate treatment effects on the individuals or to estimate average treatment effects, including finding dual-objective optimal crossover designs. 

Abstract MotivationModeling single-cell gene expression trends along cell pseudotime is a crucial analysis for exploring biological processes. Most existing methods rely on nonparametric regression models for their flexibility; however, nonparametric models often provide trends too complex to interpret. Other existing methods use interpretable but restrictive models. Since model interpretability and flexibility are both indispensable for understanding biological processes, the single-cell field needs a model that improves the interpretability and largely maintains the flexibility of nonparametric regression models. ResultsHere, we propose the single-cell generalized trend model (scGTM) for capturing a gene’s expression trend, which may be monotone, hill-shaped or valley-shaped, along cell pseudotime. The scGTM has three advantages: (i) it can capture non-monotonic trends that are easy to interpret, (ii) its parameters are biologically interpretable and trend informative, and (iii) it can flexibly accommodate common distributions for modeling gene expression counts. To tackle the complex optimization problems, we use the particle swarm optimization algorithm to find the constrained maximum likelihood estimates for the scGTM parameters. As an application, we analyze several single-cell gene expression datasets using the scGTM and show that scGTM can capture interpretable gene expression trends along cell pseudotime and reveal molecular insights underlying biological processes. Availability and implementationThe Python package scGTM is open-access and available at https://github.com/ElvisCuiHan/scGTM. Supplementary informationSupplementary data are available at Bioinformatics online. 

Abstract The aim of this article is to provide an overview of the orthogonal array composite design (OACD) methodology, illustrate the various advantages, and provide a real‐world application. An OACD combines a two‐level factorial design with a three‐level orthogonal array and it can be used as an alternative to existing composite designs for building response surface models. We compare the ‐efficiencies of OACDs relative to the commonly used central composite design (CCD) when there are a few missing observations and demonstrate that OACDs are more robust to missing observations for two scenarios. The first scenario assumes one missing observation either from one factorial point or one additional point. The second scenario assumes two missing observations either from two factorial points or from two additional points, or from one factorial point and one additional point. Furthermore, we compare OACDs and CCDs in terms of ‐optimality for precise predictions. Lastly, a real‐world application of an OACD for a tuberculosis drug combination study is provided. 

Abstract BackgroundIdiopathic pulmonary fibrosis (IPF) is a progressive, irreversible, and usually fatal lung disease of unknown reasons, generally affecting the elderly population. Early diagnosis of IPF is crucial for triaging patients’ treatment planning into anti‐fibrotic treatment or treatments for other causes of pulmonary fibrosis. However, current IPF diagnosis workflow is complicated and time‐consuming, which involves collaborative efforts from radiologists, pathologists, and clinicians and it is largely subject to inter‐observer variability. PurposeThe purpose of this work is to develop a deep learning‐based automated system that can diagnose subjects with IPF among subjects with interstitial lung disease (ILD) using an axial chest computed tomography (CT) scan. This work can potentially enable timely diagnosis decisions and reduce inter‐observer variability. MethodsOur dataset contains CT scans from 349 IPF patients and 529 non‐IPF ILD patients. We used 80% of the dataset for training and validation purposes and 20% as the holdout test set. We proposed a two‐stage model: at stage one, we built a multi‐scale, domain knowledge‐guided attention model (MSGA) that encouraged the model to focus on specific areas of interest to enhance model explainability, including both high‐ and medium‐resolution attentions; at stage two, we collected the output from MSGA and constructed a random forest (RF) classifier for patient‐level diagnosis, to further boost model accuracy. RF classifier is utilized as a final decision stage since it is interpretable, computationally fast, and can handle correlated variables. Model utility was examined by (1) accuracy, represented by the area under the receiver operating characteristic curve (AUC) with standard deviation (SD), and (2) explainability, illustrated by the visual examination of the estimated attention maps which showed the important areas for model diagnostics. ResultsDuring the training and validation stage, we observe that when we provide no guidance from domain knowledge, the IPF diagnosis model reaches acceptable performance (AUC±SD = 0.93±0.07), but lacks explainability; when including only guided high‐ or medium‐resolution attention, the learned attention maps are not satisfactory; when including both high‐ and medium‐resolution attention, under certain hyperparameter settings, the model reaches the highest AUC among all experiments (AUC±SD = 0.99±0.01) and the estimated attention maps concentrate on the regions of interests for this task. Three best‐performing hyperparameter selections according to MSGA were applied to the holdout test set and reached comparable model performance to that of the validation set. ConclusionsOur results suggest that, for a task with only scan‐level labels available, MSGA+RF can utilize the population‐level domain knowledge to guide the training of the network, which increases both model accuracy and explainability.