High-dimensional Statistics Applications to Batch Effects in Metabolomics

Batch effects are inevitable in large-scale metabolomics. Prior to formal data analysis, batch effect correction (BEC) is applied to prevent from obscuring biological variations, and batch effect evaluation (BEE) is used for correction assessment. However, existing BEE algorithms neglect covariances between the variables, and existing BEC algorithms might fail to adequately correct the covariances. Therefore, we resort to recent advancements in high-dimensional statistics, and respectively propose "quality control-based simultaneous tests (QC-ST)" and "covariance correction (CoCo)". Validated by the simulation data, QC-ST can simultaneously detect the statistical significance of QC samples' mean vectors and covariance matrices across different batches, and has a satisfactory statistical performance in empirical sizes, empirical powers, and computational speed. Then, we apply four QC-based BEC algorithms to two large cohort datasets, and find that extreme gradient boost (XGBoost) performs best in relative standard deviation (RSD) and dispersion-ratio (D-ratio). After prepositive BEC, if QC-ST still suggests that batch effects between some two batches are significant, CoCo should be implemented. And after CoCo (if necessary), the four metrics (i.e., RSD, D-ratio, classification performance, and QC-ST) might be further improved. In summary, under the guidance of QC-ST, we can develop a matching strategy to integrate multiple BEC algorithms more rationally and flexibly, and minimize batch effects for reliable biological conclusions.

Photoacoustic Microscopy with Sparse Data Enabled by Convolutional Neural Networks for Fast Imaging

Photoacoustic microscopy (PAM) has been a promising biomedical imaging technology in recent years. However, the point-by-point scanning mechanism results in low-speed imaging, which limits the application of PAM. Reducing sampling density can naturally shorten image acquisition time, which is at the cost of image quality. In this work, we propose a method using convolutional neural networks (CNNs) to improve the quality of sparse PAM images, thereby speeding up image acquisition while keeping good image quality. The CNN model utilizes both squeeze-and-excitation blocks and residual blocks to achieve the enhancement, which is a mapping from a 1/4 or 1/16 low-sampling sparse PAM image to a latent fully-sampled image. The perceptual loss function is applied to keep the fidelity of images. The model is mainly trained and validated on PAM images of leaf veins. The experiments show the effectiveness of our proposed method, which significantly outperforms existing methods quantitatively and qualitatively. Our model is also tested using in vivo PAM images of blood vessels of mouse ears and eyes. The results show that the model can enhance the image quality of the sparse PAM image of blood vessels from several aspects, which may help fast PAM and facilitate its clinical applications.