Identifying Phenotypes Based on TCR Repertoire Using Machine Learning Methods

The adaptive immune system can prevent human beings being infected by pathogens. T cells, a kind of lymphocytes in the adaptive immunity, recognise antigens by T cell receptors (TCRs) and then generate cell-mediated immune responses. After primary immune responses, the adaptive immunity can generate corresponding immunological memory. TCRs are generated by a process of somatic gene rearrangement and therefore have high diversity. An individual's TCR repertoire can reveal his pathogen exposure history, which can assist in biological studies such as disease diagnosis. This master thesis targets to make predictions about phenotype statuses based on high-throughput TCR sequencing data using machine learning approaches, to see how accurate the phenotype identification based on TCR repertoire can be. The raw TCR data is preprocessed in three different ways and then proceed the next steps separately. Several feature selection approaches are applied to obtain the most important TCRs. The machine learning algorithms including Beta-binomial model (baseline), Logistic regression, Random forest and a Boosting algorithm LightGBM are trained and evaluated. Two datasets, Cytomegalovirus (CMV) and rheumatoid arthritis (RA), are explored. For the CMV dataset, Random forest performs best, even though only a little bit better than the baseline model. However, the classification results of the RA dataset are not so good whatever models used, and the best classifier is LightGBM. The results imply that the TCR data needs to be large enough to make powerful predictions. Using a sufficiently large dataset, the prediction ability of the baseline model is great, and there may exist certain algorithms such as Random forest outperform it

Growth Modeling in a Diagnostic Classification Model (DCM) Framework–A Multivariate Longitudinal Diagnostic Classification Model

This work is licensed under a Creative Commons Attribution 4.0 International License.A multivariate longitudinal DCM is developed that is the composite of two components, the log-linear cognitive diagnostic model (LCDM) as the measurement model component that evaluates the mastery status of attributes at each measurement occasion, and a generalized multivariate growth curve model that describes the growth of each attribute over time. The proposed model represents an improvement in the current longitudinal DCMs given its ability to incorporate both balanced and unbalanced data and to measure the growth of a single attribute directly without assuming that attributes grow in the same pattern. One simulation study was conducted to evaluate the proposed model in terms of the convergence rates, the accuracy of classification, and parameter recoveries under different combinations of four design factors: the sample size, the growth patterns, the G matrix design, and the number of measurement occasions. The results revealed the following: (1) In general, the proposed model provided good convergence rates under different conditions. (2) Regarding the classification accuracy, the proposed model achieved good recoveries on the probabilities of attribute mastery. However, the correct classification rates depended on the cut point that was used to classify individuals. For individuals who truly mastered the attributes, the correct classification rates increased as the measurement occasions increased; however, for individuals who truly did not master the attributes, the correct classification rates decreased slightly as the numbers of measurement occasions increased. Cohen's kappa increased as the number of measurement occasions increased. (3) Both the intercept and main effect parameters in the LCDM were recovered well. The interaction effect parameters had a relatively large bias under the condition with a small sample size and fewer measurement occasions; however, the recoveries were improved as the sample size and the number of measurement occasions increased. (4) Overall, the proposed model achieved acceptable recoveries on both the fixed and random effects in the generalized growth curve model

Searching for economic and cosmopolitan roots: the historical discourse of “Hankou Merchant Port Nostalgia” in the central Chinese City of Wuhan 武汉

This paper has two main lines of investigation: firstly, we shall explore the process by which selective remembering, histories and heritage are converted into new form of competitive urban cultural capital; secondly, this paper points to the critical dangers and problematics that emerge when selective remembering and historic urban branding lead to the production of new urban landscapes and commercial spaces; as we shall demonstrate, selective remembering and branding can sabotage and displace communities, informal economies,histories, lives and subjectivities

Immediate Antiretroviral Therapy Decreases Mortality Among Patients With High CD4 Counts in China: A Nationwide, Retrospective Cohort Study.

BackgroundClinical trials have demonstrated that immediate initiation of antiretroviral therapy (ART) reduces AIDS-related morbidity and mortality. We tested the hypothesis that initiating ART ≤30 days after human immunodeficiency virus (HIV) diagnosis would be associated with reduced mortality among people living with HIV (PLWH) with CD4 counts >500 cells/μL.MethodsPLWH enrolled in the Chinese National HIV Information System between January 2012 and June 2014 with CD4 counts >500 cells/μL were followed for 12 months. Cox proportional hazards model was used to determine hazard ratios (HRs) for PLWH who initiated ART after HIV diagnosis. ART initiation was treated as a time-dependent variable.ResultsWe enrolled 34581 PLWH with CD4 >500 cells/μL; 1838 (5.3%) initiated ART ≤30 days after diagnosis (immediate ART group), and 19 deaths were observed with a mortality rate of 1.04 per 100 person-years (PY). Fifty-eight deaths were documented among the 5640 PLWH in the delayed ART group with a mortality rate of 2.25 per 100 PY. There were 713 deaths among the 27103 PLWH in the no ART group with a mortality rate of 2.39 per 100 PY. After controlling for potential confounding factors, ART initiation at ≤30 days (adjusted HR, 0.37 [95% confidence interval, .23-.58]) was a statistically significant protective factor.ConclusionsWe found that immediate ART is associated with a 63% reduction in overall mortality among PLWH with CD4 counts >500 cells/μL in China, supporting the recommendation to initiate ART immediately following HIV diagnosis

The Application of Membrane Separation Technology in the Dairy Industry

Dairy industry is considered as an important food industry that provides various kinds of nutritionally rich dairy products for all age groups. Beside these nutritive values, dairy industry is contemplated as a good source of raw materials for other industries. Most importantly, dairy industry employs environment-friendly and energy-saving technologies. Membrane separation technology being one of those also focused on a cost-effective and environment-friendly manner, which can be widely applied in dairy industry for many useful purposes. In this chapter, we first define and classify the membrane separation technology and then comprehensively describe its applications, for instance, component separation, filtration, removal of bacteria, and wastewater treatment in dairy industry

Changing trend of HIV, Syphilis and Hepatitis C among Men Who Have Sex with Men in China

Dearth of information regarding the trend and correlates of HIV, syphilis and Hepatitis C (HCV) in a country-wide sample of understudied though high-risk Chinese men who have sex with men (MSM) called for a comprehensive serial cross-sectional study. Using a multistage mixed-method strategy, 171,311 MSM from 107 selected cities/counties in 30 provinces of mainland China, were interviewed and tested. Descriptive, bivariate, multivariate and Cochran-Armitage trend analyses were conducted using SAS 9.2. During 2009-13, recent (71.5% to 78.6%, p < 0.001) and consistent (40.4% to 48.8%, p < 0.001) condom use as well as condom use during commercial anal sex (46.5% to 55.0%, p < 0.001) were increasing. In contrast, commercial anal sex with male (11.9% to 7.1%, p < 0.001) and drug use (1.9% to 0.8%, p < 0.001) were decreasing over time. HIV prevalence increased gradually (5.5% to 7.3%, p < 0.001), while syphilis (9.0% to 6.3%, p < 0.001) and HCV prevalence (1.5% to 0.7%, p < 0.001) decreased over time. A positive correlation was observed between HIV and syphilis prevalence (r = 0.38). HIV infection was associated with HIV-related knowledge, services and injecting drug use. An increasing trend of HIV prevalence was observed during 2009–13 among MSM in China. While gradual reduction of risk behaviors along with syphilis and HCV prevalence supported expansion of testing and prevention services, increasing HIV burden called for deeper thematic investigations

Baseline CD4 Cell Counts of Newly Diagnosed HIV Cases in China: 2006–2012

Background: Late diagnosis of HIV infection is common. We aim to assess the proportion of newly diagnosed HIV cases receiving timely baseline CD4 count testing and the associated factors in China. Methods: Data were extracted from the Chinese HIV/AIDS Comprehensive Response Information Management System. Adult patients over 15 years old who had been newly diagnosed with HIV infection in China between 2006 and 2012 were identified. The study cohort comprised individuals who had a measured baseline CD4 count. Results: Among 388,496 newly identified HIV cases, the median baseline CD4 count was 294 cells/µl (IQR: 130–454), and over half (N = 130,442, 58.8%) were less than 350 cells/µl. The median baseline CD4 count increased from 221 (IQR: 63–410) in 2006 to 314 (IQR: 159–460) in 2012. A slight majority of patients (N = 221,980, 57.1%) received baseline CD4 count testing within 6 months of diagnosis. The proportion of individuals who received timely baseline CD4 count testing increased significantly from 20.0% in 2006 to 76.9% in 2012. Factors associated with failing to receiving timely CD4 count testing were: being male (OR: 1.17, 95% CI: 1.15–1.19), age 55 years or older (OR:1.03, 95% CI: 1.00–1.06), educational attainment of primary school education or below (OR: 1.30, 95% CI: 1.28–1.32), infection with HIV through injection drug use (OR: 2.07, 95% CI: 2.02–2.12) or sexual contact and injection drug use (OR: 1.87, 95% CI: 1.76–1.99), diagnosis in a hospital (OR: 1.91, 95% CI: 1.88–1.95) or in a detention center (OR: 1.75, 95% CI: 1.70–1.80), and employment as a migrant worker (OR:1.55, 95% CI:1.53–1.58). Conclusion: The proportion of newly identified HIV patients receiving timely baseline CD4 testing has increased significantly in China from 2006–2012. Continued effort is needed for further promotion of early HIV diagnosis and timely baseline CD4 cell count testing

Spatial Analysis of the Human Immunodeficiency Virus Epidemic among Men Who Have Sex with Men in China, 2006–2015

Background: Studies have shown a recent upsurge in human immunodeficiency virus (HIV) burden among men who have sex with men (MSM) in China, especially in urban areas. For intervention planning and resource allocation, spatial analyses of HIV/AIDS case-clusters were required to identify epidemic foci and trends among MSM in China. Methods: Information regarding MSM recorded as HIV/AIDS cases during 2006-2015 were extracted from the National Case Reporting System. Demographic trends were determined through Cochran-Armitage trend tests. Distribution of case-clusters was examined using spatial autocorrelation. Spatial-temporal scan was used to detect disease clustering. Spatial correlations between cases and socioenvironmental factors were determined by spatial regression. Results: Between 2006 and 2015, in China, 120 371 HIV/AIDS cases were identified among MSM. Newly identified HIV/AIDS cases among self-reported MSM increased from 487 cases in 2006 to >30 000 cases in 2015. Among those HIV/AIDS cases recorded during 2006-2015, 47.0% were 20-29 years old and 24.9% were aged 30-39 years. Based on clusters of HIV/AIDS cases identified through spatial analysis, the epidemic was concentrated among MSM in large cities. Spatial-temporal clusters contained municipalities, provincial capitals, and main cities such as Beijing, Shanghai, Chongqing, Chengdu, and Guangzhou. Spatial regression analysis showed that sociodemographic indicators such as population density, per capita gross domestic product, and number of county-level medical institutions had statistically significant positive correlations with HIV/AIDS among MSM. Conclusions: Assorted spatial analyses revealed an increasingly concentrated HIV epidemic among young MSM in Chinese cities, calling for targeted health education and intensive interventions at an early age

Penicillium marneffei-Stimulated Dendritic Cells Enhance HIV-1 Trans-Infection and Promote Viral Infection by Activating Primary CD4+ T Cells

Penicillium marneffei (P. marneffei) is considered an indicator pathogen of AIDS, and the endemicity and clinical features of P. marneffei have been described. While, how the co-infection of P. marneffei exacerbate deterioration of the immune response remains poorly understood. Here we isolated P. marneffei from the cutaneous lesions of AIDS patients and analyzed its effects on HIV-1-dendritic cells (DCs) interaction. We demonstrated that the monocyte-derived dendritic cells (MDDCs) could be activated by both thermally dimorphic forms of P. marneffei for significantly promoting HIV-1 trans-infection of CD4+ T cells, while these activated MDDCs were refractory to HIV-1 infection. Mechanistically, P. marneffei-activated MDDCs endocytosed large amounts of HIV-1 and sequestrated the internalized viruses into tetrapasnin CD81+ compartments potentially for proteolysis escaping. The activated MDDCs increased expression of intercellular adhesion molecule 1 and facilitated the formation of DC-T-cell conjunctions, where much more viruses were recruited. Moreover, we found that P. marneffei-stimulated MDDCs efficiently activated resting CD4+ T cells and induced more susceptible targets for viral infection. Our findings demonstrate that DC function and its interaction with HIV-1 have been modulated by opportunistic pathogens such as P. marneffei for viral dissemination and infection amplification, highlighting the importance of understanding DC-HIV-1 interaction for viral immunopathogenesis elucidation