Despite the availabilty of imaging-based and mass-spectrometry-based methods for spatial proteomics, a key challenge remains connecting images with single-cell-resolution protein abundance measurements. Here, we introduce Deep Visual Proteomics (DVP), which combines artificial-intelligence-driven image analysis of cellular phenotypes with automated single-cell or single-nucleus laser microdissection and ultra-high-sensitivity mass spectrometry. DVP links protein abundance to complex cellular or subcellular phenotypes while preserving spatial context. By individually excising nuclei from cell culture, we classified distinct cell states with proteomic profiles defined by known and uncharacterized proteins. In an archived primary melanoma tissue, DVP identified spatially resolved proteome changes as normal melanocytes transition to fully invasive melanoma, revealing pathways that change in a spatial manner as cancer progresses, such as mRNA splicing dysregulation in metastatic vertical growth that coincides with reduced interferon signaling and antigen presentation. The ability of DVP to retain precise spatial proteomic information in the tissue context has implications for the molecular profiling of clinical samples.
Highlights d Robust method automatically adapting to various unseen experimental scenarios d Deep learning solution for accurate nucleus segmentation without user interaction d Accelerates, improves quality, and reduces complexity of bioimage analysis tasks
Uremic cardiomyopathy is characterized by diastolic dysfunction (DD), left ventricular hypertrophy (LVH), and fibrosis. Angiotensin-II plays a major role in the development of uremic cardiomyopathy via nitro-oxidative and inflammatory mechanisms. In heart failure, the beta-3 adrenergic receptor (β3-AR) is up-regulated and coupled to endothelial nitric oxide synthase (eNOS)-mediated pathways, exerting antiremodeling effects. We aimed to compare the antiremodeling effects of the angiotensin-II receptor blocker losartan and the β3-AR agonist mirabegron in uremic cardiomyopathy. Chronic kidney disease (CKD) was induced by 5/6th nephrectomy in male Wistar rats. Five weeks later, rats were randomized into four groups: (1) sham-operated, (2) CKD, (3) losartan-treated (10 mg/kg/day) CKD, and (4) mirabegron-treated (10 mg/kg/day) CKD groups. At week 13, echocardiographic, histologic, laboratory, qRT-PCR, and Western blot measurements proved the development of uremic cardiomyopathy with DD, LVH, fibrosis, inflammation, and reduced eNOS levels, which were significantly ameliorated by losartan. However, mirabegron showed a tendency to decrease DD and fibrosis; but eNOS expression remained reduced. In uremic cardiomyopathy, β3-AR, sarcoplasmic reticulum ATPase (SERCA), and phospholamban levels did not change irrespective of treatments. Mirabegron reduced the angiotensin-II receptor 1 expression in uremic cardiomyopathy that might explain its mild antiremodeling effects despite the unchanged expression of the β3-AR.
A real-time method for fetal heart rate (FHR) monitoring based on signal processing of the fetal heart sounds is presented. The acoustic method, which utilizes an adaptive time pattern analysis to select and analyze those heartbeats that can be recorded without artefact, is guided by a number of rules involving an introduced confidence factor on the timing prediction. The algorithm was implemented in a low-power portable electronic instrument to enable long-term fetal surveillance. A large number of clinical tests have shown the very good performance of the phonocardiographic method in comparison with FHR curves simultaneously recorded with ultrasound cardiotocography. Indeed, approximately 90% of the time, the acoustic FHR curve remained inside a +/- 3 beats/min tolerance limit of the reference ultrasound method. The confidence was typically CF > 0.85. The acoustic method exceeded a +/- 5 beats/min limit relative to the ultrasound method approximately 5% of the time. Finally, no relevant FHR data was measured approximately 5% of the time.
Surface Electromyography (sEMG/EMG) is to record muscles' electrical activity from a restricted area of the skin by using electrodes. The sEMG-based gesture recognition is extremely sensitive of inter-session and inter-subject variances. We propose a model and a deep-learning-based domain adaptation method to approximate the domain shift for recognition accuracy enhancement. Analysis performed on sparse and High-Density (HD) sEMG public datasets validate that our approach outperforms state-of-the-art methods.
GI patient status is associated with depressive and anxiety symptoms, in addition IBS patients have more severe depressive symptoms and depressogenic dysfunctional attitudes. The fact that functional GI patients are characterized by more severe psychological, but not social parameters, supports the hypothesis that IBS might be related to the range of depressive disorders.
Single cell segmentation is typically one of the first and most crucial tasks of image-based cellular analysis. We present a deep learning approach aiming towards a truly general method for localizing nuclei across a diverse range of assays and light microscopy modalities. We outperform the 739 methods submitted to the 2018 Data Science Bowl on images representing a variety of realistic conditions, some of which were not represented in the training data. The key to our approach is to adapt our model to unseen and unlabeled data using image style transfer to generate augmented training samples. This allows the model to recognize nuclei in new and different experiments without requiring expert annotations.Identifying nuclei is the starting point for many microscopy-based cellular analyses. Accurate localization of the nucleus is the basis of a variety of quantitative measurements, but is also a first step for identifying individual cell borders, which enables a multitude of further analyses. Until recently, the dominant approaches for this task have been based on classic image processing algorithms (e.g. CellProfiler 1 ) which were sometimes guided by shape and spatial priors 2 . A drawback of these methods is the need for expert knowledge to properly adjust the parameters, which typically must be re-tuned when experimental conditions change.Recently, deep learning has revolutionized an assortment of tasks in image analysis, from image classification 3 to face recognition 4 , and scene segmentation 5 . It is also responsible for breakthroughs in diagnosing retinal images 6 , classifying skin lesions with superhuman performance 7 , as well as incredible advances in 3D fluorescence image analysis 8 . However, aside from initial works from Caicedo et al. 9 and Van Valen et al. 10 , deep learning has yet to significantly advance nucleus segmentation performance.
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