ABSTRACT
BACKGROUND: For complex diseases like cancer, pooled-analysis of individual data represents a powerful tool to investigate the joint contribution of genetic, phenotypic and environmental factors to the development of a disease. Pooled-analysis of epidemiological studies has many advantages over meta-analysis, and preliminary results may be obtained faster and with lower costs than with prospective consortia. DESIGN AND METHODS: Based on our experience with the study design of the Melanocortin-1 receptor (MC1R) gene, SKin cancer and Phenotypic characteristics (M-SKIP) project, we describe the most important steps in planning and conducting a pooled-analysis of genetic epidemiological studies. We then present the statistical analysis plan that we are going to apply, giving particular attention to methods of analysis recently proposed to account for between-study heterogeneity and to explore the joint contribution of genetic, phenotypic and environmental factors in the development of a disease. Within the M-SKIP project, data on 10,959 skin cancer cases and 14,785 controls from 31 international investigators were checked for quality and recoded for standardization. We first proposed to fit the aggregated data with random-effects logistic regression models. However, for the M-SKIP project, a two-stage analysis will be preferred to overcome the problem regarding the availability of different study covariates. The joint contribution of MC1R variants and phenotypic characteristics to skin cancer development will be studied via logic regression modeling. DISCUSSION: Methodological guidelines to correctly design and conduct pooled-analyses are needed to facilitate application of such methods, thus providing a better summary of the actual findings on specific fields.
Subject(s)
Epidemiologic Research Design , Genetic Predisposition to Disease , Receptor, Melanocortin, Type 1 , Skin Neoplasms/genetics , Sunlight/adverse effects , Adult , Case-Control Studies , Data Collection/standards , Data Interpretation, Statistical , Female , Hospitalization , Humans , Logistic Models , Male , Meta-Analysis as Topic , Phenotype , Skin Neoplasms/physiopathology , Skin Neoplasms/secondary , SmokingABSTRACT
Introduction: Coronavirus disease (COVID-19) rapidly spread from Wuhan, China to other parts of China and other regions/countries around the world, resulting in a pandemic due to large populations moving through the massive transport hubs connecting all regions of China via railways and a major international airport. COVID-19 will remain a threat until safe and effective vaccines and antiviral drugs have been developed, distributed, and administered on a global scale. Thus, there is urgent need to establish effective implementation of preemptive non-pharmaceutical interventions for appropriate prevention and control strategies, and predicting future COVID-19 cases is required to monitor and control the issue. Methods: This study attempts to utilize a three-layer graph convolutional network (GCN) model to predict future COVID-19 cases in 190 regions and countries using COVID-19 case data, commercial flight route data, and digital maps of public transportation in terms of transnational human mobility. We compared the performance of the proposed GCN model to a multilayer perceptron (MLP) model on a dataset of COVID-19 cases (excluding the graph representation). The prediction performance of the models was evaluated using the mean squared error. Results: Our results demonstrate that the proposed GCN model can achieve better graph utilization and performance compared to the baseline in terms of both prediction accuracy and stability. Discussion: The proposed GCN model is a useful means to predict COVID-19 cases at regional and national levels. Such predictions can be used to facilitate public health solutions in public health responses to the COVID-19 pandemic using deep learning and data pooling. In addition, the proposed GCN model may help public health policymakers in decision making in terms of epidemic prevention and control strategies.
Subject(s)
COVID-19 , Pandemics , COVID-19/epidemiology , Forecasting , Humans , Neural Networks, Computer , Public HealthABSTRACT
Early warning systems (EWS) have been proposed as a measure for controlling and preventing dengue fever outbreaks in countries where this infection is endemic. A vaccine is not available and has yet to reach the market due to the economic burden of development, introduction and safety concerns. Understanding how dengue spreads and identifying the risk factors will facilitate the development of a dengue EWS, for which a climate-based model is still needed. An analysis was conducted to examine emerging spatiotemporal hotspots of dengue fever at the township level in Taiwan, associated with climatic factors obtained from remotely sensed data in order to identify the risk factors. Machinelearning was applied to support the search for factors with a spatiotemporal correlation with dengue fever outbreaks. Three dengue fever hotspot categories were found in southwest Taiwan and shown to be spatiotemporally associated with five kinds of sea surface temperatures. Machine-learning, based on the deep AlexNet model trained by transfer learning, yielded an accuracy of 100% on an 8-fold cross-validation test dataset of longitudetime sea surface temperature images.
Subject(s)
Climate , Dengue/epidemiology , Machine Learning , Spatio-Temporal Analysis , Disease Outbreaks , Geographic Information Systems , Humans , Reproducibility of Results , Risk Factors , Taiwan/epidemiology , TemperatureABSTRACT
The aim of the present study was to identify geographical areas and time periods of potential clusters of dengue cases based on ecological, socio-economic and demographic factors in northern Sri Lanka from January 2010 to December 2013. Remote sensing (RS) was used to develop an index comprising rainfall, humidity and temperature data. Remote sensing data gathered by the AVNIR-2 instrument onboard the ALOS satellite were used to detect urbanisation, and a digital land cover map was used to extract land cover information. Other data on relevant factors and dengue outbreaks were collected through institutions and extant databases. The analysed RS data and databases were integrated into a geographical information system (GIS) enabling space-time clustering analysis. Our results indicate that increases in the number of combinations of ecological, socio-economic and demographic factors that are present or above the average contribute to significantly high rates of space-time dengue clusters. The spatio-temporal association that consolidates the two kinds of associations into one can ensure a more stable model for forecasting. An integrated spatiotemporal prediction model at a smaller level using ecological, socioeconomic and demographic factors could lead to substantial improvements in dengue control and prevention by allocating the right resources to the appropriate places at the right time.
Subject(s)
Dengue/epidemiology , Remote Sensing Technology , Satellite Imagery , Climate , Demography , Disease Outbreaks , Humans , Retrospective Studies , Socioeconomic Factors , Space-Time Clustering , Sri Lanka/epidemiology , Topography, MedicalABSTRACT
Genetic and environmental factors are both part of an elaborate feedback mechanism whereby the human adaptive form reacts to environmental stimuli via internal adjustments. Human survival may ultimately depend on understanding two important components of future environmental adaptation. First, we must elucidate the dynamics of the human genome underpinning the complex human phenotype. Second, we must understand how the environment pressures and affects the genome, helping to determine human traits. This article reviews current approaches to detecting the natural selection of skin color variation in human populations. We include statistical methods for clarifying gene-environment interactions applicable to the interactions with UV radiation levels. We recommend spatial data mining as an efficient approach that applies environmental association rules, extending our knowledge of adaptation to the environment.
Subject(s)
Adaptation, Biological/genetics , Genetic Variation , Skin Pigmentation/genetics , Environment , Gene Expression , Humans , Phenotype , Polymorphism, Single Nucleotide , Selection, Genetic , Ultraviolet RaysABSTRACT
This study aimed to identify single nucleotide polymorphism (SNP) alleles at multiple loci associated with racial differences in skin color using SNP genotyping. A total of 122 Caucasians in Toledo, Ohio and 100 Mongoloids in Japan were genotyped for 20 SNPs in 7 candidate genes, encoding the Agouti signaling protein (ASIP), tyrosinase-related protein 1 (TYRP1), tyrosinase (TYR), melanocortin 1 receptor (MC1R), oculocutaneous albinism II (OCA2), microphthalmia-associated transcription factor (MITF), and myosin VA (MYO5A). Data were used to analyze associations between the 20 SNP alleles using linkage disequilibrium (LD). Combinations of SNP alleles were jointly tested under LD for associations with racial groups by performing a chi(2) test for independence. Results showed that SNP alleles at multiple loci can be considered the haplotype that contributes to significant differences between the two population groups and suggest a high probability of LD. Confirmation of these findings requires further study with other ethnic groups to analyze the associations between SNP alleles at multiple loci and skin color variation among races.
Subject(s)
Asian People/genetics , Monophenol Monooxygenase/genetics , Skin Pigmentation/genetics , White People/genetics , Agouti Signaling Protein/genetics , Alleles , Back , Cheek , Humans , Japan , Linkage Disequilibrium/genetics , Membrane Glycoproteins/genetics , Membrane Transport Proteins/genetics , Microphthalmia-Associated Transcription Factor/genetics , Myosin Heavy Chains/genetics , Myosin Type V/genetics , Ohio , Oxidoreductases/genetics , Polymorphism, Single Nucleotide , Receptor, Melanocortin, Type 1/geneticsABSTRACT
This study was undertaken to clarify the molecular basis for human skin color variation and the environmental adaptability to ultraviolet irradiation, with the ultimate goal of predicting the impact of changes in future environments on human health risk. One hundred twenty-two Caucasians living in Toledo, Ohio participated. Back and cheek skin were assayed for melanin as a quantitative trait marker. Buccal cell samples were collected and used for DNA extraction. DNA was used for SNP genotyping using the Masscode system, which entails two-step PCR amplification and a platform chemistry which allows cleavable mass spectrometry tags. The results show gene-gene interaction between SNP alleles at multiple loci (not necessarily on the same chromosome) contributes to inter-individual skin color variation while suggesting a high probability of linkage disequilibrium. Confirmation of these findings requires further study with other ethic groups to analyze the associations between SNP alleles at multiple loci and human skin color variation. Our overarching goal is to use remote sensing data to clarify the interaction between atmospheric environments and SNP allelic frequency and investigate human adaptability to ultraviolet irradiation. Such information should greatly assist in the prediction of the health effects of future environmental changes such as ozone depletion and increased ultraviolet exposure. If such health effects are to some extent predictable, it might be possible to prepare for such changes in advance and thus reduce the extent of their impact.
ABSTRACT
We present a conceptual framework for applying techniques of SNP genotyping as a molecular biological approach and remote sensing as an ecological approach to elucidation of the contribution of polygene and environmental factors to inter-individual variation in skin pigmentation phenotype. Additionally, we discuss the obstacles that frustrate our efforts to identify how the human genome encodes the complex phenotype and suggest the use of computational methods designed for knowledge discovery within hereditary database.