The emergence of viral epidemics throughout the world is of concern due to the scarcity of available effective antiviral therapeutics. The discovery of new antiviral therapies is imperative to address this challenge, and antiviral peptides (AVPs) represent a valuable resource for the development of novel therapies to combat viral infection. We present a new machine learning model to distinguish AVPs from non-AVPs using the most informative features derived from the physicochemical and structural properties of their amino acid sequences. To focus on those features that are most likely to contribute to antiviral performance, we filter potential features based on their importance for classification. These feature selection analyses suggest that secondary structure is the most important peptide sequence feature for predicting AVPs. Our Feature-Informed Reduced Machine Learning for Antiviral Peptide Prediction (FIRM-AVP) approach achieves a higher accuracy than either the model with all features or current state-of-the-art single classifiers. Understanding the features that are associated with AVP activity is a core need to identify and design new AVPs in novel systems. The FIRM-AVP code and standalone software package are available at https://github.com/pmartR/FIRM-AVP with an accompanying web application at https://msc-viz.emsl.pnnl.gov/AVPR.

Summary Here we introduce Lipid Mini-On, an open-source tool that performs lipid enrichment analyses and visualizations of lipidomics data. Lipid Mini-On uses a text-mining process to bin individual lipid names into multiple lipid ontology groups based on the classification (e.g. LipidMaps) and other characteristics, such as chain length. Lipid Mini-On provides users with the capability to conduct enrichment analysis of the lipid ontology terms using a Shiny app with options of five statistical approaches. Lipid classes can be added to customize the user’s database and remain updated as new lipid classes are discovered. Visualization of results is available for all classification options (e.g. lipid subclass and individual fatty acid chains). Results are also visualized through an editable network of relationships between the individual lipids and their associated lipid ontology terms. The utility of the tool is demonstrated using biological (e.g. human lung endothelial cells) and environmental (e.g. peat soil) samples. Availability and implementation Rodin (R package: https://github.com/PNNL-Comp-Mass-Spec/Rodin), Lipid Mini-On Shiny app (https://github.com/PNNL-Comp-Mass-Spec/LipidMiniOn) and Lipid Mini-On online tool (https://omicstools.pnnl.gov/shiny/lipid-mini-on/). Supplementary information Supplementary data are available at Bioinformatics online.

Background: The Environmental Determinants of the Diabetes in the Young (TEDDY) study has prospectively followed, from birth, children at increased genetic risk of type 1 diabetes. TEDDY has collected heterogenous data longitudinally to gain insights into the environmental and biological mechanisms driving the progression to persistent islet autoantibodies. Methods: We developed a machine learning model to predict imminent transition to the development of persistent islet autoantibodies based on timevarying metabolomics data integrated with time-invariant risk factors (eg, gestational age). The machine learning was initiated with 221 potential features (85 genetic, 5 environmental, 131 metabolomic) and an ensemble-based feature evaluation was utilized to identify a small set of predictive features that can be interrogated to better understand the pathogenesis leading up to persistent islet autoimmunity. Results: The final integrative machine learning model included 42 disparate features, returning a cross-validated receiver operating characteristic area under the curve (AUC) of 0.74 and an AUC of 0.65 on an independent validation dataset. The model identified a principal set of 20 time-invariant markers, including 18 genetic markers (16 single nucleotide polymorphisms [SNPs] and two HLA-DR genotypes) and two demographic markers (gestational age and exposure to a prebiotic formula). Integration with the metabolome identified 22 supplemental metabolites and lipids, including adipic acid and ceramide d42:0, that predicted development of islet autoantibodies. Conclusions: The majority (86%) of metabolites that predicted development of islet autoantibodies belonged to three pathways: lipid oxidation, phospholipase A2 signaling, and pentose phosphate, suggesting that these metabolic processes may play a role in triggering islet autoimmunity.

Classification is a common technique applied to ’omics data to build predictive models and identify potential markers of biomedical outcomes. Despite the prevalence of case-control studies, the number of classification methods available to analyze data generated by such studies is extremely limited. Conditional logistic regression is the most commonly used technique, but the associated modeling assumptions limit its ability to identify a large class of sufficiently complicated ’omic signatures. We propose a data preprocessing step which generalizes and makes any linear or nonlinear classification algorithm, even those typically not appropriate for matched design data, available to be used to model case-control data and identify relevant biomarkers in these study designs. We demonstrate on simulated case-control data that both the classification and variable selection accuracy of each method is improved after applying this processing step and that the proposed methods are comparable to or outperform existing variable selection methods. Finally, we demonstrate the impact of conditional classification algorithms on a large cohort study of children with islet autoimmunity.

Subsampled image acquisition followed by image inpainting in a scanning transmission electron microscope is a novel approach to control dose and increase the image frame rate during experiments, thereby allowing independent control of the spatial and temporal dose envelope during image acquisition. Here, subsampled imaging is shown to permit precise in situ observations of the fundamental kinetic processes behind nucleation and growth of silver (Ag) nanoparticles from an aqueous solution. At high sampling-levels, nanoparticles can be observed with morphologies that are consistent with strong interface interactions, i.e., rafts and pillars, whereas at low sampling-levels, the particles exhibit regular spherical morphologies. The relative numbers of rafts/pillars and regular nanoparticles, their sizes, and their incubation times can be attributed to local changes in the molar concentration of the Ag ions in the aqueous solution; higher sampling-levels significantly increase the reactants in the vicinity of the window, leading to rapid supersaturation and the precipitation on the window surface. These precisely controlled kinetics highlight subsampled imaging as a method by which the driving force for nucleation and growth (i.e., the electron beam) can be disentangled from the spatial/temporal resolution of the observation in all in situ experiments, providing a pathway to identify and quantify the importance of individual kinetic factors behind nucleation and growth in a wide variety of complex materials systems and architectures.