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Single-cell RNA sequencing provides unprecedent opportunities to explore the heterogeneity and dynamics inherent in cellular biology. An essential step in the data analysis involves the automatic annotation of cells. Despite development of numerous tools for automated cell annotation, assessing the reliability of predicted annotations remains challenging, particularly for rare and unknown cell types. Here, we introduce VICTOR: Validation and inspection of cell type annotation through optimal regression. VICTOR aims to gauge the confidence of cell annotations by an elastic-net regularized regression with optimal thresholds. We demonstrated that VICTOR performed well in identifying inaccurate annotations, surpassing existing methods in diagnostic ability across various single-cell datasets, including within-platform, cross-platform, cross-studies, and cross-omics settings.

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With recent advances in machine learning, we demonstrated the use of supervised machine learning to optimize the prediction of treatment outcomes of vedolizumab through iterative optimization using VARSITY and VISIBLE 1 data in patients with moderate-to-severe ulcerative colitis. The analysis was carried out using elastic net regularized regression following a 2-stage training process. The model performance was assessed through AUROC, specificity, sensitivity, and accuracy. The generalizable predictive patterns suggest that easily obtained baseline and medical history variables may be able to predict therapeutic response to vedolizumab with clinically meaningful accuracy, implying a potential for individualized prescription of vedolizumab.

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Several studies using magnetic resonance imaging (MRI) scans have shown developmental trajectories of cortical thickness. Cognitive milestones happen concurrently with these structural changes, and a delay in such changes has been implicated in developmental disorders such as attention-deficit/hyperactivity disorder (ADHD). Accurate estimation of individuals' brain maturity, therefore, is critical in establishing a baseline for normal brain development against which neurodevelopmental disorders can be assessed. In this study, cortical thickness derived from structural magnetic resonance imaging (MRI) scans of a large longitudinal dataset of normally growing children and adolescents (n=308), were used to build a highly accurate predictive model for estimating chronological age (cross-validated correlation up to R=0.84). Unlike previous studies which used kernelized approach in building prediction models, we used an elastic net penalized linear regression model capable of producing a spatially sparse, yet accurate predictive model of chronological age. Upon investigating different scales of cortical parcellation from 78 to 10,240 brain parcels, we observed that the accuracy in estimated age improved with increased spatial scale of brain parcellation, with the best estimations obtained for spatial resolutions consisting of 2560 and 10,240 brain parcels. The top predictors of brain maturity were found in highly localized sensorimotor and association areas. The results of our study demonstrate that cortical thickness can be used to estimate individuals' brain maturity with high accuracy, and the estimated ages relate to functional and behavioural measures, underscoring the relevance and scope of the study in the understanding of biological maturity.

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