We present a joint model based on deep learning that is designed to inpaint the missing-wedge sinogram of electron tomography and reduce the residual artifacts in the reconstructed tomograms. Traditional methods, such as weighted back projection (WBP) and simultaneous algebraic reconstruction technique (SART), lack the ability to recover the unacquired project information as a result of the limited tilt range; consequently, the tomograms reconstructed using these methods are distorted and contaminated with the elongation, streaking, and ghost tail artifacts. To tackle this problem, we first design a sinogram filling model based on the use of Residual-in-Residual Dense Blocks in a Generative Adversarial Network (GAN). Then, we use a U-net structured Generative Adversarial Network to reduce the residual artifacts. We build a two-step model to perform information recovery and artifacts removal in their respective suitable domain. Compared with the traditional methods, our method offers superior Peak Signal to Noise Ratio (PSNR) and the Structural Similarity Index (SSIM) to WBP and SART; even with a missing wedge of 45°, our method offers reconstructed images that closely resemble the ground truth with nearly no artifacts. In addition, our model has the advantage of not needing inputs from human operators or setting hyperparameters such as iteration steps and relaxation coefficient used in TV-based methods, which highly relies on human experience and parameter fine turning.

Brown adipose tissue (BAT) regulates metabolic physiology. However, nearly all mechanistic studies of BAT protein function occur in a single inbred mouse strain, which has limited the understanding of generalizable mechanisms of BAT regulation over physiology. Here, we perform deep quantitative proteomics of BAT across a cohort of 163 genetically defined diversity outbred mice, a model that parallels the genetic and phenotypic variation found in humans. We leverage this diversity to define the functional architecture of the outbred BAT proteome, comprising 10,479 proteins. We assign co-operative functions to 2,578 proteins, enabling systematic discovery of regulators of BAT. We also identify 638 proteins that correlate with protection from, or sensitivity to, at least one parameter of metabolic disease. We use these findings to uncover SFXN5, LETMD1, and ATP1A2 as modulators of BAT thermogenesis or adiposity, and provide OPABAT as a resource for understanding the conserved mechanisms of BAT regulation over metabolic physiology.