Deep Learning in Proteomics Wen, Bo; Zeng, Wen‐Feng; Liao, Yuxing ...
Proteomics,
November 2020, Letnik:
20, Številka:
21-22
Journal Article
Recenzirano
Odprti dostop
Proteomics, the study of all the proteins in biological systems, is becoming a data‐rich science. Protein sequences and structures are comprehensively catalogued in online databases. With recent ...advancements in tandem mass spectrometry (MS) technology, protein expression and post‐translational modifications (PTMs) can be studied in a variety of biological systems at the global scale. Sophisticated computational algorithms are needed to translate the vast amount of data into novel biological insights. Deep learning automatically extracts data representations at high levels of ion from data, and it thrives in data‐rich scientific research domains. Here, a comprehensive overview of deep learning applications in proteomics, including retention time prediction, MS/MS spectrum prediction, de novo peptide sequencing, PTM prediction, major histocompatibility complex‐peptide binding prediction, and protein structure prediction, is provided. Limitations and the future directions of deep learning in proteomics are also discussed. This review will provide readers an overview of deep learning and how it can be used to analyze proteomics data.
Cyclodextrin-based polymers (CDPs) are amphiphilic macromolecules owing to their unique structure and the presence of multiple hydroxyl groups. These polymers have become increasingly popular in ...applications ranging from biomedicine to environmental science. In this review, four types of CDPs are distinguished based on their structural characteristics: cyclodextrin-based polyrotaxanes, grafted cyclodextrin polymers, cross-linked cyclodextrin polymers, and cyclodextrin-originated star/multi-arm polymers. The discussion includes the syntheses and properties of several derivatives of CDPs. In addition to low toxicity, good bioavailability and biodegradability, and the feasibility of inclusion complexation and chemical modification of cyclodextrins, these polymers have prominent advantages, such as stimuli responsiveness and the ability to form well-defined aggregated nanostructures, which make them promising candidates for applications related to controlled and targeted drug delivery. In this review, we have highlighted the evolution, unique types, and properties of various CDPs, which are core aspects that differ from previously published reviews. Additionally, the synergistic effect of cyclodextrin and cross-linking monomers, as well as their use as drug carriers over the past decade, have been emphasized.
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Studies have shown that the combined application of hyaluronic acid (HA) and platelet-rich plasma (PRP) can repair degenerated cartilage and delay the progression of knee osteoarthritis (KOA). The ...purpose of this study was to explore the efficacy and safety of the intra-articular injection of PRP combined with HA compared with the intra-articular injection of PRP or HA alone in the treatment of KOA.
The PubMed, Cochrane Library, EMBASE and China National Knowledge Infrastructure (CNKI) databases were searched from inception to December 2019. Randomized controlled trials and cohort studies of PRP combined with HA for KOA were included. Two orthopaedic surgeons conducted the literature retrieval and extracted the data. Outcome indicators included the Western Ontario and McMaster Universities Arthritis Index (WOMAC), the Lequesne Index, the visual analogue scale (VAS) for pain, and adverse events (AEs). Review Manager 5.3 was used to calculate the relative risk (RR) or standardized mean difference (SMD) of the pooled data. STATA 14.0 was used for quantitative publication bias evaluation.
Seven studies (5 randomized controlled trials, 2 cohort studies) with a total of 941 patients were included. In the VAS comparison after 6 months of follow-up, PRP combined with HA was more likely to reduce knee pain than PRP alone (SMD: - 0.31; 95% confidence interval (CI): - 0.55 to - 0.06; P = 0.01 < 0.05). PRP combined with HA for KOA achieved better improvements in the WOMAC Function Score (SMD: -0.32; 95% CI: - 0.54 to - 0.10; P < 0.05) and WOMAC Total Score (SMD: -0.42; 95% CI: - 0.67 to - 0.17; P < 0.05) at the 12-month follow-up than did the application of PRP alone. In a comparison of Lequesne Index scores at the 6-month follow-up, PRP combined with HA improved knee pain scores more than PRP alone (SMD: -0.42; 95% CI: - 0.67 to - 0.17; P < 0.05). In terms of AEs, PRP combined with HA was not significantly different from PRP or HA alone (P > 0.05).
Compared with intra-articular injection of PRP alone, that of PRP combined with HA can improve the WOMAC Function Scores, WOMAC Total Score, 6-month follow-up VAS ratings, and Lequesne Index scores. However, in terms of the incidence of AEs, PRP combined with HA is not significantly different from PRP or HA alone.
As a promising new paradigm, Vehicular Edge Computing (VEC) can improve the QoS of vehicular applications by computation offloading. However, with more and more computation-intensive vehicular ...applications, VEC servers face the challenges of limited resources. In this paper, we study how to effectively and economically utilize the idle resources in volunteer vehicles to handle the overloaded tasks in VEC servers. First, we present a model of volunteer assisted vehicular edge computing, in which the cost and utility functions are defined for requesting vehicles and VEC servers, and volunteer vehicles are encouraged to assist the overloaded VEC servers via obtaining rewards from VEC servers. Then, based on Stackelberg game, we analyze the interactions between requesting vehicles and VEC servers, and find the optimal strategies for them. Furthermore, we prove theoretically that the Stackelberg game between requesting vehicles and VEC servers has a unique Stackelberg equilibrium, and propose a fast searching algorithm based on genetic algorithm to find the best pricing strategy for the VEC server. In addition, to maximize the reward of volunteer vehicles, we propose the volunteer task assignment algorithm for optimal mapping between the tasks and volunteer alliances. Finally, the effectiveness of the proposed scheme is demonstrated through a large number of simulations. Compared with other schemes, the proposed scheme can reduce the offloading cost of vehicles and improve the utility of VEC servers.
The Coronavirus Disease (COVID-19) pandemic first broke out in December 2019 in Wuhan, China, and has now spread worldwide. Laboratory findings have been only partially described in some ...observational studies. To date, more comprehensive systematic reviews of laboratory findings on COVID-19 are missing. We performed a systematic review with a meta-analysis to assess laboratory findings in patients with COVID-19. Observational studies from three databases were selected. We calculated pooled proportions and 95% confidence interval (95% CI) using the random-effects model meta-analysis. A total of 1106 articles were identified from PubMed, Web of Science, CNKI (China), and other sources. After screening, 28 and 7 studies were selected for a systematic review and a meta-analysis, respectively. Of the 4,663 patients included, the most prevalent laboratory finding was increased C-reactive protein (CRP; 73.6%, 95% CI 65.0-81.3%), followed by decreased albumin (62.9%, 95% CI 28.3-91.2%), increased erythrocyte sedimentation rate (61.2%, 95% CI 41.3-81.0%), decreased eosinophils (58.4%, 95% CI 46.5-69.8%), increased interleukin-6 (53.1%, 95% CI 36.0-70.0%), lymphopenia (47.9%, 95% CI 41.6-54.9%), and increased lactate dehydrogenase (LDH; 46.2%, 95% CI 37.9-54.7%). A meta-analysis of seven studies with 1905 patients showed that increased CRP (OR 3.0, 95% CI: 2.1-4.4), lymphopenia (OR 4.5, 95% CI: 3.3-6.0), and increased LDH (OR 6.7, 95% CI: 2.4-18.9) were significantly associated with severity. These results demonstrated that more attention is warranted when interpreting laboratory findings in patients with COVID-19. Patients with elevated CRP levels, lymphopenia, or elevated LDH require proper management and, if necessary, transfer to the intensive care unit.
We describe pLink 2, a search engine with higher speed and reliability for proteome-scale identification of cross-linked peptides. With a two-stage open search strategy facilitated by fragment ...indexing, pLink 2 is ~40 times faster than pLink 1 and 3~10 times faster than Kojak. Furthermore, using simulated datasets, synthetic datasets,
N metabolically labeled datasets, and entrapment databases, four analysis methods were designed to evaluate the credibility of ten state-of-the-art search engines. This systematic evaluation shows that pLink 2 outperforms these methods in precision and sensitivity, especially at proteome scales. Lastly, re-analysis of four published proteome-scale cross-linking datasets with pLink 2 required only a fraction of the time used by pLink 1, with up to 27% more cross-linked residue pairs identified. pLink 2 is therefore an efficient and reliable tool for cross-linking mass spectrometry analysis, and the systematic evaluation methods described here will be useful for future software development.
Gastrointestinal stromal tumors (GISTs), KIT or platelet derived growth factor receptor alpha (PDGFRA) signaling driven mesenchymal tumors of the gastrointestinal (GI)-tract and abdomen, require a ...precise diagnosis so that the patients may benefit from the newly introduced tyrosine kinase inhibitor drugs. The limitations of the current main tools, KIT immunohistochemistry and KIT/PDGFRA mutation analysis, include lack of KIT expression and mutations in some GISTs. In this study we examined 1168 GISTs of different sites and histologic subtypes, and 672 other tumors and normal tissues for discovered on GIST-1 (DOG1) clone K9, a newly introduced immunohistochemical marker, a chloride channel protein. All GISTs and selected non-GISTs were independently evaluated for KIT. In the GI tract, Cajal cells and gastric surface epithelia were DOG1-positive. The overall sensitivity of DOG1 and KIT in GISTs was nearly identical: 94.4% and 94.7%, and results in GISTs were generally concordant. Gastric spindle cell GISTs was nearly uniformly positive for both markers, whereas DOG1 performed slightly better in gastric epithelioid GISTs that included PDGFRA mutant GISTs. In the intestinal GISTs, KIT was slightly more sensitive than DOG1. Negativity for both DOG1 and KIT was observed in 2.6% of GISTs of GI tract. KIT or PDGFRA mutations were detected in 11/24 DOG1-negative GISTs supporting the diagnosis of GIST. DOG1 expression was also generally present in extragastrointestinal and metastatic GISTs. DOG1 was highly specific for GIST, but exceptional DOG1-positive other mesenchymal tumors included uterine type retroperitoneal leiomyomas, peritoneal leiomyomatosis, and synovial sarcomas (positive in 5/42, 4/17, and 6/37 cases). Leiomyomas colonized by DOG1-positive Cajal cells should not be confused with GISTs. DOG1 positivity was relatively common in esophageal squamous cell and gastric carcinomas, whereas it was rare in colorectal carcinomas. DOG1 should be added into the diagnostic panel evaluating GI and other abdominal tumors, but limitations in its sensitivity and specificity should be recognized.
Carbon dots (Cdots) are an important probe for imaging and sensing applications because of their fluorescence property, good biocompatibility, and low toxicity. However, complex procedures and strong ...acid treatment are often required and Cdots suffer from low photoluminescence (PL) emission. Herein, a facile and general strategy using carbonization of precursors and then extraction with solvents is proposed for the preparation of nitrogen‐doped Cdots (N‐Cdots) with 3‐(3,4‐dihydroxyphenyl)‐L‐alanine (L‐DOPA), L‐histidine, and L‐arginine as precursor models. After they are heated, the precursors become carbonized. Nitrogen‐doped Cdots are subsequently extracted into N,N′‐dimethylformamide (DMF) from the carbogenic solid. A core–shell structure of Cdots with a carbon core and the oxygen‐containing shell was observed. Nitrogen has different forms in N‐Cdots and oxidized N‐Cdots. The doped nitrogen and low oxidation level in N‐Cdots improve their emission significantly. The N‐Cdots show an emission with a nitrogen‐content‐dependent intensity and Cdot‐size‐dependent emission‐peak wavelength. Imaging of HeLa cells, a human cervical cancer cell line, and HepG2 cells, a human hepatocellular liver carcinoma line, was observed with high resolution using N‐Cdots as a probe and validates their use in imaging applications and their multicolor property in the living cell system.
Going dotty: A facile and general strategy involving the carbonization of precursors and their subsequent extraction with solvents is proposed for the preparation of nitrogen‐doped carbon dots (N‐Cdots) with multicolor emission (see figure). The emission mechanism of the Cdots was studied. Multicolor photoluminescence was validated in living cell systems.
The recent revolution in computational protein structure prediction provides folding models for entire proteomes, which can now be integrated with large-scale experimental data. Mass spectrometry ...(MS)-based proteomics has identified and quantified tens of thousands of posttranslational modifications (PTMs), most of them of uncertain functional relevance. In this study, we determine the structural context of these PTMs and investigate how this information can be leveraged to pinpoint potential regulatory sites. Our analysis uncovers global patterns of PTM occurrence across folded and intrinsically disordered regions. We found that this information can help to distinguish regulatory PTMs from those marking improperly folded proteins. Interestingly, the human proteome contains thousands of proteins that have large folded domains linked by short, disordered regions that are strongly enriched in regulatory phosphosites. These include well-known kinase activation loops that induce protein conformational changes upon phosphorylation. This regulatory mechanism appears to be widespread in kinases but also occurs in other protein families such as solute carriers. It is not limited to phosphorylation but includes ubiquitination and acetylation sites as well. Furthermore, we performed three-dimensional proximity analysis, which revealed examples of spatial coregulation of different PTM types and potential PTM crosstalk. To enable the community to build upon these first analyses, we provide tools for 3D visualization of proteomics data and PTMs as well as python libraries for data accession and processing.
Nevus sebaceus (NS) is a congenital hamartoma of skin structures including the epidermis, sweat sebaceous glands, and hair follicles. It is known that secondary tumors can occur in NS. However, ...secondary metastatic malignancies are rare. Basosquamous carcinoma (BSC) is an aggressive type of basal cell carcinoma (BCC) characterized by squamous differentiation. Herein, we report a case of metastatic BSC that developed in a 73‐year‐old male with NS. The clinical presentation of this patient was that of an ulcerative nodule developing in a longstanding plaque‐like lesion consistent with NS. Histopathological examination revealed characteristic features of BCC with some areas of squamous differentiation in addition to the structure of a typical NS. Immunohistochemical expression of Ber‐EP4, AE1/AE3, and epithelial membrane antigen helped to make the diagnosis of BSC.
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