DE-MHAIPs: Identification of SARS-CoV-2 phosphorylation sites based on differential evolution multi-feature learning and multi-head attention mechanism

The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) around the world affects the normal lives of people all over the world. The computational methods can be used to accurately identify SARS-CoV-2 phosphorylation sites. In this paper, a new prediction model of SARS-CoV-2 phosphorylation sites, called DE-MHAIPs, is proposed. First, we use six feature extraction methods to extract protein sequence information from different perspectives. For the first time, we use a differential evolution (DE) algorithm to learn individual feature weights and fuse multi-information in a weighted combination. Next, Group LASSO is used to select a subset of good features. Then, the important protein information is given higher weight through multi-head attention. After that, the processed data is fed into long short-term memory network (LSTM) to further enhance model's ability to learn features. Finally, the data from LSTM are input into fully connected neural network (FCN) to predict SARS-CoV-2 phosphorylation sites. The AUC values of the S/T and Y datasets under 5-fold cross-validation reach 91.98% and 98.32%, respectively. The AUC values of the two datasets on the independent test set reach 91.72% and 97.78%, respectively. The experimental results show that the DE-MHAIPs method exhibits excellent predictive ability compared with other methods.

Corrigendum to "Comprehensive Humoral and Cellular Immune Responses to SARS-CoV-2 Variants in Diverse Chinese Population".

[This corrects the article DOI: 10.34133/2022/9873831.].

Dual-Gene-Controlled Rolling Circle Amplification Strategy for SARS-CoV-2 Analysis.

The development of sensitive, accurate, and conveniently operated methods for the simultaneous assay of two nucleic acids is promising while still challenging. In this work, by using two genes (the N gene and RdRp gene) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as examples, we have designed an ingenious dual-gene-controlled rolling circle amplification (RCA) strategy to propose an accurate and sensitive electrochemical method. Specifically, the coexistence of the two target genes can trigger the RCA reaction to generate a number of repeated G-quadruplex (G4)-forming sequences. These sequences then switch into G4/hemin complexes with redox activity after the incubation of hemin, which can catalyze the TMB/H2O2 substrates to produce significantly enhanced current responses. Experimental results reveal that the proposed method exhibits satisfying feasibility and analytical performance, enabling the sensitive detection of SARS-CoV-2 in the range of 0.1-5000 pM, with the detection limit of 57 fM. Meanwhile, because only the simultaneous existence of the two target genes can effectively trigger the downstream amplification reaction, this method can effectively avoid false-positives and ensure specificity as well as accuracy. Furthermore, our method can distinguish the COVID-19 samples from healthy people, and the outcomes show a satisfying agreement with the results of RT-PCR, manifesting that our label-free dual-gene-controlled RCA strategy exhibits great possibility in clinical application.

An electrochemical biosensor for SARS-CoV-2 detection via its papain-like cysteine protease and the protease inhibitor screening.

The persistent coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is still infecting hundreds of thousands of people every day. Enriching the kits for SARS-CoV-2 detection and developing the drugs for patient treatments are still urgently needed for combating the spreading virus, especially after the emergence of various mutants. Herein, an electrochemical biosensor has been fabricated in this work for the detection of SARS-CoV-2 via its papain-like cysteine protease (PLpro) and the screening of protease inhibitor against SARS-CoV-2 by using our designed chimeric peptide-DNA (pDNA) nanoprobes. Utilizing this biosensor, the sensitive and specific detection of SARS-CoV-2 PLpro can be conducted in complex real environments including blood and saliva. Five positive and five negative patient throat swab samples have also been tested to verify the practical application capability of the biosensor. Moreover, we have obtained a detection limit of 27.18 fM and a linear detection range from 1 pg mL-1 to 10 µg mL-1 (I = 1.63 + 4.44 lgC). Meanwhile, rapid inhibitor screening against SARS-CoV-2 PLpro can be also obtained. Therefore, this electrochemical biosensor has the great potential for COVID-19 combating and drug development.

Comprehensive Humoral and Cellular Immune Responses to SARS-CoV-2 Variants in Diverse Chinese Population.

The SARS-CoV-2 variants have been emerging and have made great challenges to current vaccine and pandemic control strategies. It is urgent to understand the current immune status of various Chinese populations given that the preexisting immunity has been established by national vaccination or exposure to past variants. Using sera from 85 individuals (including 21 convalescents of natural infection, 15 cases which suffered a breakthrough infection after being fully vaccinated, and 49 healthy vaccinees), we showed significantly enhanced neutralizing activities against SRAS-CoV-2 variants in convalescent sera, especially those who had been fully vaccinated. The neutralizing antibodies against Omicron were detectable in 75% of convalescents and 44.9% of healthy vaccinees (p = 0.006), with a GMT of 289.5, 180.9-463.3, and 42.6, 31.3-59, respectively. However, the neutralizing activities were weaker in young convalescents (aged < 18 y), with a detectable rate of 50% and a GMT of 46.4 against Omicron. We also examined and found no pan-sarbecovirus neutralizing activities in vaccinated SARS-CoV-1 survivors. A booster dose could further increase the breadth and magnitude of neutralization against WT and variants of concern (VOCs) to different degrees. In addition, we showed that COVID-19-inactivated vaccines can elicit Omicron-specific T-cell responses. The positive rates of ELISpot reactions were 26.7% (4/15) and 43.8% (7/16) in the full vaccination group and the booster vaccination group, respectively, although without statistically significant difference. The neutralizing antibody titers declined while T-cell responses remain consistent over 6 months. These findings will inform the optimization of public health vaccination and intervention strategies to protect diverse populations against SARS-CoV-2 variants. Advances. Breakthrough infection significantly boosted neutralizing activities against SARS-CoV-2 variants as compared to booster immunization with inactivated vaccine. Vaccine-induced virus-specific T-cell immunity, on the other hand, may compensate for the shortfall. Furthermore, the public health system should target the most vulnerable group due to a poorer protective serological response in both infected and vaccinated adolescents.

Sex disparities in influenza: A multiscale network analysis

Summary Sex differences in the pathogenesis of infectious diseases because of differential immune responses between females and males have been well-documented for multiple pathogens. However, the molecular mechanism underlying the observed sex differences in influenza virus infection remains poorly understood. In this study, we used a network-based approach to characterize the blood transcriptome collected over the course of infection with influenza A virus from female and male ferrets to dissect sex-biased gene expression. We identified significant differences in the temporal dynamics and regulation of immune responses between females and males. Our results elucidate sex-differentiated pathways involved in the unfolded protein response (UPR), lipid metabolism, and inflammatory responses, including a female-biased IRE1/XBP1 activation and male-biased crosstalk between metabolic reprogramming and IL-1 and AP-1 pathways. Overall, our study provides molecular insights into sex differences in transcriptional regulation of immune responses and contributes to a better understanding of sex biases in influenza pathogenesis. Graphical Highlights • Regulation of immune responses between females and males is significantly different• Rapid activation of UPR in females triggers potent immune and inflammatory responses• Male-specific regulatory pattern in the AP1 pathway indicate a bias in immune response Biological sciences;Immunology;Virology;Systems biology

Target-triggered cascade signal amplification for sensitive electrochemical detection of SARS-CoV-2 with clinical application.

The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the outbreak of the 2019 coronavirus (COVID-19) disease, which greatly challenges the global economy and health. Simple and sensitive diagnosis of COVID-19 at the early stage is important to prevent the spread of pandemics. Herein, we have proposed a target-triggered cascade signal amplification in this work for sensitive analysis of SARS-CoV-2 RNA. Specifically, the presence of SARS-CoV-2 RNA can trigger the catalytic hairpin assembly to generate plenty of DNA duplexes with free 3'-OH termini, which can be recognized and catalyzed by the terminal deoxynucleotidyl transferase (TdT) to generate long strand DNA. The prolonged DNA can absorb substantial Ru(NH3)63+ molecules via electrostatic interaction and produce an enhanced current response. The incorporation of catalytic hairpin assembly and TdT-mediated polymerization effectively lowers the detection limit to 45 fM, with a wide linear range from 0.1 pM to 3000 pM. Moreover, the proposed strategy possesses excellent selectivity to distinguish target RNA with single-base mismatched, three-base mismatched, and random sequences. Notably, the proposed electrochemical biosensor can be applied to analyze targets in complex circumstances containing 10% saliva, which implies its high stability and anti-interference. Moreover, the proposed strategy has been successfully applied to SARS CoV-2 RNA detection in clinical samples and may have the potential to be cultivated as an effective tool for COVID-19 diagnosis.

Visual naked-eye detection of SARS-CoV-2 RNA based on covalent organic framework capsules.

The ongoing outbreak of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has highlighted that new diagnosis technologies are crucial for controlling the spread of the disease. Especially in the resources-limit region, conveniently operated detection methods such as "naked-eye" detection are urgently required that no instrument is needed. Herein, we have designed a novel and facile strategy to fabricate covalent organic framework (COF) capsules, which can be utilized to establish a new colorimetric assay for naked-eye detection of SARS-CoV-2 RNA. Specifically, we employ the digestible ZIF-90 as the sacrificial template to prepare the hollow COF capsules for horseradish peroxidase (HRP) encapsulation. The fabricated COF capsules can provide an appropriate microenvironment for the enzyme molecules, which may improve the conformational freedom of enzymes, enhance the mass transfer, and endow the enzyme with high environmental resistance. With such design, the proposed assay exhibits outstanding analytical performance for the detection of SARS-CoV-2 RNA in the linear range from 5 pM to 50 nM with a detection limit of 0.28 pM which can go parallel to qTR-PCR analysis. Our method also possesses excellent selectivity and reproducibility. Moreover, this method can also be served to analyze the clinical samples, and can successfully differentiate COVID-19 patients from healthy people, suggesting the promising potential in clinical diagnosis.

Risk factors for mortality of coronavirus disease-2019 (COVID-19) patients in two centers of Hubei province, China: A retrospective analysis.

PURPOSE: Since the outbreak in late December 2019 in Wuhan, China, coronavirus disease-2019 (COVID-19) has become a global pandemic. We analyzed and compared the clinical, laboratory, and radiological characteristics between survivors and non-survivors and identify risk factors for mortality. METHODS: Clinical and laboratory variables, radiological features, treatment approach, and complications were retrospectively collected in two centers of Hubei province, China. Cox regression analysis was conducted to identify the risk factors for mortality. RESULTS: A total of 432 patients were enrolled, and the median patient age was 54 years. The overall mortality rate was 5.09% (22/432). As compared with the survivor group (n = 410), those in the non-survivor group (n = 22) were older, and they had a higher frequency of comorbidities and were more prone to suffer from dyspnea. Several abnormal laboratory variables indicated that acute cardiac injury, hepatic damage, and acute renal insufficiency were detected in the non-survivor group. Non-surviving patients also had a high computed tomography (CT) score and higher rate of consolidation. The most common complication causing death was acute respiratory distress syndrome (ARDS) (18/22, 81.8%). Multivariate Cox regression analysis revealed that hemoglobin (Hb) <90 g/L (hazard ratio, 10.776; 95% confidence interval, 3.075-37.766; p<0.0001), creatine kinase (CK-MB) >8 U/L (9.155; 2.424-34.584; p = 0.001), lactate dehydrogenase (LDH) >245 U/L (5.963; 2.029-17.529; p = 0.001), procalcitonin (PCT) >0.5 ng/ml (7.080; 1.671-29.992; p = 0.008), and CT score >10 (39.503; 12.430-125.539; p<0.0001) were independent risk factors for the mortality of COVID-19. CONCLUSIONS: Low Hb, high LDH, PCT, and CT score on admission were the predictors for mortality and could assist clinicians in early identification of poor prognosis among COVID-19 patients.

Association between cytokine profiles and lung injury in COVID-19 pneumonia.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a new respiratory and systemic disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The purpose of the present study was to investigate the association between cytokine profiles and lung injury in COVID-19 pneumonia. METHODS: This retrospective study was conducted in COVID-19 patients. Demographic characteristics, symptoms, signs, underlying diseases, and laboratory data were collected. The patients were divided into COVID-19 with pneumonia and without pneumonia. CT severity score and PaO2/FiO2 ratio were used to assess lung injury. RESULTS: 106 patients with 12 COVID-19 without pneumonia and 94 COVID-19 with pneumonia were included. Compared with COVID-19 without pneumonia, COVID-19 with pneumonia had significantly higher serum interleukin (IL)-2R, IL-6, and tumor necrosis factor (TNF)-α. Correlation analysis showed that CT severity score and PaO2/FiO2 were significantly correlated with age, presence of any coexisting disorder, lymphocyte count, procalcitonin, IL-2R, and IL-6. In multivariate analysis, log IL6 was the only independent explanatory variables for CT severity score (ß = 0.397, p < 0.001) and PaO2/FiO2 (ß = - 0.434, p = 0.003). CONCLUSIONS: Elevation of circulating cytokines was significantly associated with presence of pneumonia in COVID-19 and the severity of lung injury in COVID-19 pneumonia. Circulating IL-6 independently predicted the severity of lung injury in COVID-19 pneumonia.