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Pep-TCRNet is a novel approach to constructing a prediction model that can evaluate the probability of recognition between a TCR and a peptide amino acid sequence while combining inputs such as TCR sequences, HLA types, and VJ genes.Pep-TCRNet operates in two key steps:Feature Engineering: This step processes different types of variables:TCR and peptide amino acid sequencing data: The model incorporates neural network architectures inspired by language representation models and graph representation model to learn the meaningful embeddings.Categorical data: Specialized encoding techniques are used to ensure optimal feature representation for HLA types and VJ genes.Prediction Model: The second step involves training a prediction model to evaluate the likelihood of a TCR recognizing a specific peptide, based on the features generated in the first step.more » « less
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Free, publicly-accessible full text available July 14, 2026
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Exploring features associated with the clinical outcome of interest is a rapidly advancing area of research. However, with contemporary sequencing technologies capable of identifying over thousands of genes per sample, there is a challenge in constructing efficient prediction models that balance accuracy and resource utilization. To address this challenge, researchers have developed feature selection methods to enhance performance, reduce overfitting, and ensure resource efficiency. However, applying feature selection models to survival analysis, particularly in clinical datasets characterized by substantial censoring and limited sample sizes, introduces unique challenges. We propose a robust ensemble feature selection approach integrated with group Lasso to identify compelling features and evaluate its performance in predicting survival outcomes. Our approach consistently outperforms established models across various criteria through extensive simulations, demonstrating low false discovery rates, high sensitivity, and high stability. Furthermore, we applied the approach to a colorectal cancer dataset from The Cancer Genome Atlas, showcasing its effectiveness by generating a composite score based on the selected genes to correctly distinguish different subtypes of the patients. In summary, our proposed approach excels in selecting impactful features from high-dimensional data, yielding better outcomes compared to contemporary state-of-the-art models.more » « less
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Abstract Vapor sensors with both high sensitivity and broad detection range are technically challenging yet highly desirable for widespread chemical sensing applications in diverse environments. Generally, an increased surface‐to‐volume ratio can effectively enhance the sensitivity to low concentrations, but often with the trade‐off of a constrained sensing range. Here, an approach is demonstrated for NH3sensor arrays with an unprecedentedly broad sensing range by introducing controllable steps on the surface of an n‐type single crystal. Step edges, serving as adsorption sites with electron‐deficient properties, are well‐defined, discrete, and electronically active. NH3molecules selectively adsorb at the step edges and nearly eliminate known trap‐like character, which is demonstrated by surface potential imaging. Consequently, the strategy can significantly boost the sensitivity of two‐terminal NH3resistance sensors on thin crystals with a few steps while simultaneously enhancing the tolerance on thick crystals with dense steps. Incorporation of these crystals into parallel sensor arrays results in ppb–to–% level detection range and a convenient linear relation between sheet conductance and semi‐log NH3concentration, allowing for the precise localization of vapor leakage. In general, the results suggest new opportunities for defect engineering of organic semiconductor crystal surfaces for purposeful vapor or chemical sensing.more » « less
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T cells represent a crucial component of the adaptive immune system and mediate anti-tumoral immunity as well as protection against infections, including respiratory viruses such as SARS-CoV-2. Next-generation sequencing of the T-cell receptors (TCRs) can be used to profile the T-cell repertoire. We developed a customized pipeline for Network Analysis of Immune Repertoire (NAIR) with advanced statistical methods to characterize and investigate changes in the landscape of TCR sequences. We first performed network analysis on the TCR sequence data based on sequence similarity. We then quantified the repertoire network by network properties and correlated it with clinical outcomes of interest. In addition, we identified (1) disease-specific/associated clusters and (2) shared clusters across samples based on our customized search algorithms and assessed their relationship with clinical outcomes such as recovery from COVID-19 infection. Furthermore, to identify disease-specific TCRs, we introduced a new metric that incorporates the clonal generation probability and the clonal abundance by using the Bayes factor to filter out the false positives. TCR-seq data from COVID-19 subjects and healthy donors were used to illustrate that the proposed approach to analyzing the network architecture of the immune repertoire can reveal potential disease-specific TCRs responsible for the immune response to infection.more » « less
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The T and B cell repertoire make up the adaptive immune system and is mainly generated through somatic V(D)J gene recombination. Thus, the VJ gene usage may be a potential prognostic or predictive biomarker. However, analysis of the adaptive immune system is challenging due to the heterogeneity of the clonotypes that make up the repertoire. To address the heterogeneity of the T and B cell repertoire, we proposed a novel ensemble feature selection approach and customized statistical learning algorithm focusing on the VJ gene usage. We applied the proposed approach to T cell receptor sequences from recovered COVID-19 patients and healthy donors, as well as a group of lung cancer patients who received immunotherapy. Our approach identified distinct VJ genes used in the COVID-19 recovered patients comparing to the healthy donors and the VJ genes associated with the clinical response in the lung cancer patients. Simulation studies show that the ensemble feature selection approach outperformed other state-of-the-art feature selection methods based on both efficiency and accuracy. It consistently yielded higher stability and sensitivity with lower false discovery rates. When integrated with different classification methods, the ensemble feature selection approach had the best prediction accuracy. In conclusion, the proposed novel approach and the integration procedure is an effective feature selection technique to aid in correctly classifying different subtypes to better understand the signatures in the adaptive immune response associated with disease or the treatment in order to improve treatment strategies.more » « less
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