scNovel: a scalable deep learning-based network for novel rare cell discovery in single-cell transcriptomics.

Single-cell RNA sequencing has achieved massive success in biological research fields. Discovering novel cell types from single-cell transcriptomics has been demonstrated to be essential in the field of biomedicine, yet is time-consuming and needs prior knowledge. With the unprecedented boom in cell atlases, auto-annotation tools have become more prevalent due to their speed, accuracy and user-friendly features. However, existing tools have mostly focused on general cell-type annotation and have not adequately addressed the challenge of discovering novel rare cell types. In this work, we introduce scNovel, a powerful deep learning-based neural network that specifically focuses on novel rare cell discovery. By testing our model on diverse datasets with different scales, protocols and degrees of imbalance, we demonstrate that scNovel significantly outperforms previous state-of-the-art novel cell detection models, reaching the most AUROC performance(the only one method whose averaged AUROC results are above 94%, up to 16.26% more comparing to the second-best method). We validate scNovel's performance on a million-scale dataset to illustrate the scalability of scNovel further. Applying scNovel on a clinical COVID-19 dataset, three potential novel subtypes of Macrophages are identified, where the COVID-related differential genes are also detected to have consistent expression patterns through deeper analysis. We believe that our proposed pipeline will be an important tool for high-throughput clinical data in a wide range of applications.

DeepKOA: a deep-learning model for predicting progression in knee osteoarthritis using multimodal magnetic resonance images from the osteoarthritis initiative.

Background: No investigations have thoroughly explored the feasibility of combining magnetic resonance (MR) images and deep-learning methods for predicting the progression of knee osteoarthritis (KOA). We thus aimed to develop a potential deep-learning model for predicting OA progression based on MR images for the clinical setting. Methods: A longitudinal case-control study was performed using data from the Foundation for the National Institutes of Health (FNIH), composed of progressive cases [182 osteoarthritis (OA) knees with both radiographic and pain progression for 24-48 months] and matched controls (182 OA knees not meeting the case definition). DeepKOA was developed through 3-dimensional (3D) DenseNet169 to predict KOA progression over 24-48 months based on sagittal intermediate-weighted turbo-spin echo sequences with fat-suppression (SAG-IW-TSE-FS), sagittal 3D dual-echo steady-state water excitation (SAG-3D-DESS-WE) and its axial and coronal multiplanar reformation, and their combined MR images with patient-level labels at baseline, 12, and 24 months to eventually determine the probability of progression. The classification performance of the DeepKOA was evaluated using 5-fold cross-validation. An X-ray-based model and traditional models that used clinical variables via multilayer perceptron were built. Combined models were also constructed, which integrated clinical variables with DeepKOA. The area under the curve (AUC) was used as the evaluation metric. Results: The performance of SAG-IW-TSE-FS in predicting OA progression was similar or higher to that of other single and combined sequences. The DeepKOA based on SAG-IW-TSE-FS achieved an AUC of 0.664 (95% CI: 0.585-0.743) at baseline, 0.739 (95% CI: 0.703-0.775) at 12 months, and 0.775 (95% CI: 0.686-0.865) at 24 months. The X-ray-based model achieved an AUC ranging from 0.573 to 0.613 at 3 time points. However, adding clinical variables to DeepKOA did not improve performance (P>0.05). Initial visualizations from gradient-weighted class activation mapping (Grad-CAM) indicated that the frequency with which the patellofemoral joint was highlighted increased as time progressed, which contrasted the trend observed in the tibiofemoral joint. The meniscus, the infrapatellar fat pad, and muscles posterior to the knee were highlighted to varying degrees. Conclusions: This study initially demonstrated the feasibility of DeepKOA in the prediction of KOA progression and identified the potential responsible structures which may enlighten the future development of more clinically practical methods.

Characteristics and Discrimination of the Commercial Chinese Four Famous Vinegars Based on Flavor Compositions.

Shanxi aged vinegar (SAV), Zhenjiang aromatic vinegar (ZAV), Sichuan bran vinegar (SBV), and Fujian monascus vinegar (FMV) are the representative Chinese traditional vinegars. However, the basic differential compositions between the four vinegars are unknown. In this study, compositions of commercial vinegar were investigated to evaluate the influence of diverse technologies on their distinct flavor. Unlike amino acids and organic acids which were mostly shared, only five volatiles were detected in all vinegars, whereas a dozen volatiles were common to each type of vinegar. The four vinegars could only be classified well with all compositions, and difference analysis suggested the most significant difference between FMV and SBV. However, SAV, ZAV, and SBV possessed similar volatile characteristics due to their common heating treatments. Further, the correlation of identification markers with vinegars stressed the contributions of the smoking process, raw materials, and Monascus inoculum to SAV, SBV, and FMV clustering, respectively. Therefore, regardless of the technology modification, this basic process supported the uniqueness of the vinegars. This study contributes to improving the standards of defining the characteristics of types of vinegar.