Precise blood proteome profiling in an undiagnosed population with COVID-19.
TL;DR: In this paper, self-sampled blood provided valuable information about the COVID-19 seroprevalence in the general population, and 276 circulating proteins were quantified by proximity extension assays in dried blood spots (DBS).
Abstract: Self-sampled blood provided valuable information about the COVID-19 seroprevalence in the general population. To enable an even deeper understanding of pathophysiological processes following SARS-CoV-2 infections, 276 circulating proteins were quantified by proximity extension assays in dried blood spots (DBS). Samples from undiagnosed individuals collected during the first wave of the pandemic were selected based on their serological immune response and matched on self-reported symptoms. We stratified these as seropositive (IgM+IgG+; N = 41) or seronegative (IgM-IgG-; N = 37), and to represent the acute (IgM+IgG-; N = 26) and convalescent phases (IgM-IgG+; N = 40). This revealed proteins from a variety of clinical processes including inflammation and immune response (MBL2, MMP3, IL2RA, FCGR2A, CCL5), haemostasis (GP1BA, VWF), stress response (ANG), virus entry (SDC4) or nerve regeneration (CHL1). The presented approach complements clinical surveys and enables a deep molecular and population-wide analysis of COVID-19 from blood specimens collected outside a hospital setting.
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TL;DR: In this article , a cost-effective and compact single-microneedle-based device is presented to collect precisely 1.1 µL of dermal interstitial fluid within minutes.
Abstract: Blood sampling is a common practice to monitor health, but it entails a series of drawbacks for patients including pain and discomfort. Thus, there is a demand for more convenient ways to obtain samples. Modern analytical techniques enable monitoring of multiple bioanalytes in smaller samples, opening possibilities for new matrices, and microsampling technologies to be adopted. Interstitial fluid (ISF) is an attractive alternative matrix that shows good correlation with plasma concentration dynamics for several analytes and can be sampled in a minimally invasive and painless manner from the skin at the point‐of‐care. However, there is currently a lack of sampling devices compatible with clinical translation. Here, to tackle state‐of‐the‐art limitations, a cost‐effective and compact single‐microneedle‐based device designed to painlessly collect precisely 1.1 µL of dermal ISF within minutes is presented. The fluid is volume‐metered, dried, and stably stored into analytical‐grade paper within the microfluidic device. The obtained sample can be mailed to a laboratory, quantitatively analyzed, and provide molecular insights comparable to blood testing. In a human study, the possibility to monitor various classes of molecular analytes is demonstrated in ISF microsamples, including caffeine, hundreds of proteins, and SARS‐CoV‐2 antibodies, some being detected in ISF for the first time.
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TL;DR: It is shown that the elastic net often outperforms the lasso, while enjoying a similar sparsity of representation, and an algorithm called LARS‐EN is proposed for computing elastic net regularization paths efficiently, much like algorithm LARS does for the lamba.
Abstract: Summary. We propose the elastic net, a new regularization and variable selection method. Real world data and a simulation study show that the elastic net often outperforms the lasso, while enjoying a similar sparsity of representation. In addition, the elastic net encourages a grouping effect, where strongly correlated predictors tend to be in or out of the model together.The elastic net is particularly useful when the number of predictors (p) is much bigger than the number of observations (n). By contrast, the lasso is not a very satisfactory variable selection method in the
16,538 citations
TL;DR: In comparative timings, the new algorithms are considerably faster than competing methods and can handle large problems and can also deal efficiently with sparse features.
Abstract: We develop fast algorithms for estimation of generalized linear models with convex penalties. The models include linear regression, two-class logistic regression, and multinomial regression problems while the penalties include l(1) (the lasso), l(2) (ridge regression) and mixtures of the two (the elastic net). The algorithms use cyclical coordinate descent, computed along a regularization path. The methods can handle large problems and can also deal efficiently with sparse features. In comparative timings we find that the new algorithms are considerably faster than competing methods.
13,656 citations
TL;DR: In this paper, a map of the human tissue proteome based on an integrated omics approach that involves quantitative transcriptomics at the tissue and organ level, combined with tissue microarray-based immunohistochemistry, to achieve spatial localization of proteins down to the single-cell level.
Abstract: Resolving the molecular details of proteome variation in the different tissues and organs of the human body will greatly increase our knowledge of human biology and disease. Here, we present a map of the human tissue proteome based on an integrated omics approach that involves quantitative transcriptomics at the tissue and organ level, combined with tissue microarray-based immunohistochemistry, to achieve spatial localization of proteins down to the single-cell level. Our tissue-based analysis detected more than 90% of the putative protein-coding genes. We used this approach to explore the human secretome, the membrane proteome, the druggable proteome, the cancer proteome, and the metabolic functions in 32 different tissues and organs. All the data are integrated in an interactive Web-based database that allows exploration of individual proteins, as well as navigation of global expression patterns, in all major tissues and organs in the human body.
9,745 citations
TL;DR: In this article, the authors discuss their experience designing and implementing a statistical computing language, which combines what they felt were useful features from two existing computer languages, and they feel that the new language provides advantages in the areas of portability, computational efficiency, memory management, and scope.
Abstract: In this article we discuss our experience designing and implementing a statistical computing language. In developing this new language, we sought to combine what we felt were useful features from two existing computer languages. We feel that the new language provides advantages in the areas of portability, computational efficiency, memory management, and scoping.
9,446 citations
TL;DR: In this article, the authors reviewed and synthesized the available evidence on asymptomatic SARS-CoV-2 infection and found that infected persons who remain as healthy played a significant role in the ongoing pandemic, but their relative number and effect have been uncertain.
Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly throughout the world since the first cases of coronavirus disease 2019 (COVID-19) were observed in December 2019 in Wuhan, China. It has been suspected that infected persons who remain asymptomatic play a significant role in the ongoing pandemic, but their relative number and effect have been uncertain. The authors sought to review and synthesize the available evidence on asymptomatic SARS-CoV-2 infection. Asymptomatic persons seem to account for approximately 40% to 45% of SARS-CoV-2 infections, and they can transmit the virus to others for an extended period, perhaps longer than 14 days. Asymptomatic infection may be associated with subclinical lung abnormalities, as detected by computed tomography. Because of the high risk for silent spread by asymptomatic persons, it is imperative that testing programs include those without symptoms. To supplement conventional diagnostic testing, which is constrained by capacity, cost, and its one-off nature, innovative tactics for public health surveillance, such as crowdsourcing digital wearable data and monitoring sewage sludge, might be helpful.
1,813 citations