Prediabetes and diabetes mellitus (preDM/DM) have become alarmingly prevalent among youth in recent years. However, simple questionnaire-based screening tools to reliably assess diabetes risk are only available for adults, not youth. As a first step in developing such a tool, we used a large-scale dataset from the National Health and Nutritional Examination Survey (NHANES) to examine the performance of a published pediatric clinical screening guideline in identifying youth with preDM/DM based on American Diabetes Association diagnostic biomarkers. We assessed the agreement between the clinical guideline and biomarker criteria using established evaluation measures (sensitivity, specificity, positive/negative predictive value, F-measure for the positive/negative preDM/DM classes, and Kappa). We also compared the performance of the guideline to those of machine learning (ML) based preDM/DM classifiers derived from the NHANES dataset. Approximately 29% of the 2858 youth in our study population had preDM/DM based on biomarker criteria. The clinical guideline had a sensitivity of 43.1% and specificity of 67.6%, positive/negative predictive values of 35.2%/74.5%, positive/negative F-measures of 38.8%/70.9%, and Kappa of 0.1 (95%CI: 0.06–0.14). The performance of the guideline varied across demographic subgroups. Some ML-based classifiers performed comparably to or better than the screening guideline, especially in identifying preDM/DM youth (p = 5.23 × 10−5).We demonstrated that a recommended pediatric clinical screening guideline did not perform well in identifying preDM/DM status among youth. Additional work is needed to develop a simple yet accurate screener for youth diabetes risk, potentially by using advanced ML methods and a wider range of clinical and behavioral health data.

Heterogeneous ensembles are an effective approach in scenarios where the ideal data type and/or individual predictor are unclear for a given problem. These ensembles have shown promise for protein function prediction (PFP), but their ability to improve PFP at a large scale is unclear. The overall goal of this study is to critically assess this ability of a variety of heterogeneous ensemble methods across a multitude of functional terms, proteins and organisms. Our results show that these methods, especially Stacking using Logistic Regression, indeed produce more accurate predictions for a variety of Gene Ontology terms differing in size and specificity. To enable the application of these methods to other related problems, we have publicly shared the HPC-enabled code underlying this work as LargeGOPred ( https://github.com/GauravPandeyLab/LargeGOPred).

Motivation Integrating multimodal data represents an effective approach to predicting biomedical characteristics, such as protein functions and disease outcomes. However, existing data integration approaches do not sufficiently address the heterogeneous semantics of multimodal data. In particular, early and intermediate approaches that rely on a uniform integrated representation reinforce the consensus among the modalities, but may lose exclusive local information. The alternative late integration approach that can address this challenge has not been systematically studied for biomedical problems. Results We propose Ensemble Integration (EI) as a novel systematic implementation of the late integration approach. EI infers local predictive models from the individual data modalities using appropriate algorithms, and uses heterogeneous ensemble algorithms to integrate these local models into a global predictive model. We also propose a novel interpretation method for EI models. We tested EI on the problems of predicting protein function from multimodal STRING data, and mortality due to COVID-19 from multimodal data in electronic health records. We found that EI accomplished its goal of producing significantly more accurate predictions than each individual modality. It also performed better than several established early integration methods for each of these problems. The interpretation of a representative EI model for COVID-19 mortality prediction identified several disease-relevant features, such as laboratory test (blood urea nitrogen (BUN) and calcium) and vital sign measurements (minimum oxygen saturation) and demographics (age). These results demonstrated the effectiveness of the EI framework for biomedical data integration and predictive modeling. Availability Code and data are available at https://github.com/GauravPandeyLab/ensemble_integration.

Spatially resolved transcriptomics is a relatively new technique that maps transcriptional information within a tissue. Analysis of these datasets is challenging because gene expression values are highly sparse due to dropout events, and there is a lack of tools to facilitate in silico detection and annotation of regions based on their molecular content. Therefore, we develop a computational tool for detecting molecular regions and region-based Missing value Imputation for Spatially Transcriptomics (MIST). We validate MIST-identified regions across multiple datasets produced by 10x Visium Spatial Transcriptomics, using manually annotated histological images as references. We benchmark MIST against a spatial k-nearest neighboring baseline and other imputation methods designed for single-cell RNA sequencing. We use holdout experiments to demonstrate that MIST accurately recovers spatial transcriptomics missing values. MIST facilitates identifying intra-tissue heterogeneity and recovering spatial gene-gene co-expression signals. Using MIST before downstream analysis thus provides unbiased region detections to facilitate annotations with the associated functional analyses and produces accurately denoised spatial gene expression profiles.