Artificial intelligence and bioinformatics analyze markers of children's transcriptional genome to predict autism spectrum disorder.

Introduction: Autism spectrum disorder (ASD), characterized by difficulties in social interaction and communication as well as restricted interests and repetitive behaviors, is extremely challenging to diagnose in toddlers. Early diagnosis and intervention are crucial however. Methods: In this study, we developed a machine learning classification model based on mRNA expression data from the peripheral blood of 128 toddlers with ASD and 126 controls. Differentially expressed genes (DEGs) between ASD and controls were identified. Results: We identified genes such as UBE4B, SPATA2 and RBM3 as DEGs, mainly involved in immune-related pathways. 21 genes were screened as key biomarkers using LASSO regression, yielding an accuracy of 86%. A neural network model based on these 21 genes achieved an AUC of 0.88. Discussion: Our findings suggest that the identified neurotransmitters and 21 immune-related biomarkers may facilitate the early diagnosis of ASD. The mRNA expression profile sheds light on the biological underpinnings of ASD in toddlers and potential biomarkers for early identification. Nevertheless, larger samples are needed to validate these biomarkers.

Application of weighted co-expression network analysis and machine learning to identify the pathological mechanism of Alzheimer's disease.

Aberrant deposits of neurofibrillary tangles (NFT), the main characteristic of Alzheimer's disease (AD), are highly related to cognitive impairment. However, the pathological mechanism of NFT formation is still unclear. This study explored differences in gene expression patterns in multiple brain regions [entorhinal, temporal, and frontal cortex (EC, TC, FC)] with distinct Braak stages (0- VI), and identified the hub genes via weighted gene co-expression network analysis (WGCNA) and machine learning. For WGCNA, consensus modules were detected and correlated with the single sample gene set enrichment analysis (ssGSEA) scores. Overlapping the differentially expressed genes (DEGs, Braak stages 0 vs. I-VI) with that in the interest module, metascape analysis, and Random Forest were conducted to explore the function of overlapping genes and obtain the most significant genes. We found that the three brain regions have high similarities in the gene expression pattern and that oxidative damage plays a vital role in NFT formation via machine learning. Through further filtering of genes from interested modules by Random Forest, we screened out key genes, such as LYN, LAPTM5, and IFI30. These key genes, including LYN, LAPTM5, and ARHGDIB, may play an important role in the development of AD through the inflammatory response pathway mediated by microglia.

The Application of Consensus Weighted Gene Co-expression Network Analysis to Comparative Transcriptome Meta-Datasets of Multiple Sclerosis in Gray and White Matter.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system characterized by demyelination, which leads to the formation of white matter lesions (WMLs) and gray matter lesions (GMLs). Recently, a large amount of transcriptomics or proteomics research works explored MS, but few studies focused on the differences and similarities between GMLs and WMLs in transcriptomics. Furthermore, there are astonishing pathological differences between WMLs and GMLs, for example, there are differences in the type and abundance of infiltrating immune cells between WMLs and GMLs. Here, we used consensus weighted gene co-expression network analysis (WGCNA), single-sample gene set enrichment analysis (ssGSEA), and machine learning methods to identify the transcriptomic differences and similarities of the MS between GMLs and WMLs, and to find the co-expression modules with significant differences or similarities between them. Through weighted co-expression network analysis and ssGSEA analysis, CD56 bright natural killer cell was identified as the key immune infiltration factor in MS, whether in GM or WM. We also found that the co-expression networks between the two groups are quite similar (density = 0.79), and 28 differentially expressed genes (DEGs) are distributed in the midnightblue module, which is most related to CD56 bright natural killer cell in GM. Simultaneously, we also found that there are huge disparities between the modules, such as divergences between darkred module and lightyellow module, and these divergences may be relevant to the functions of the genes in the modules.

Application of Machine Learning and Weighted Gene Co-expression Network Algorithm to Explore the Hub Genes in the Aging Brain.

Aging is a major risk factor contributing to neurodegeneration and dementia. However, it remains unclarified how aging promotes these diseases. Here, we use machine learning and weighted gene co-expression network (WGCNA) to explore the relationship between aging and gene expression in the human frontal cortex and reveal potential biomarkers and therapeutic targets of neurodegeneration and dementia related to aging. The transcriptional profiling data of the human frontal cortex from individuals ranging from 26 to 106 years old was obtained from the GEO database in NCBI. Self-Organizing Feature Map (SOM) was conducted to find the clusters in which gene expressions downregulate with aging. For WGCNA analysis, first, co-expressed genes were clustered into different modules, and modules of interest were identified through calculating the correlation coefficient between the module and phenotypic trait (age). Next, the overlapping genes between differentially expressed genes (DEG, between young and aged group) and genes in the module of interest were discovered. Random Forest classifier was performed to obtain the most significant genes in the overlapping genes. The disclosed significant genes were further identified through network analysis. Through WGCNA analysis, the greenyellow module is found to be highly negatively correlated with age, and functions mainly in long-term potentiation and calcium signaling pathways. Through step-by-step filtering of the module genes by overlapping with downregulated DEGs in aged group and Random Forest classifier analysis, we found that MAPT, KLHDC3, RAP2A, RAP2B, ELAVL2, and SYN1 were co-expressed and highly correlated with aging.

[Epidemiological survey and risk factor analysis of asthma in children in urban districts of Zhengzhou, China].

OBJECTIVE: To study the epidemiological features, treatment status, and risk factors for asthma in children in Zhengzhou, China. METHODS: Questionnaires for primary screening were issued using the method of multi-stage stratified sampling. Suspected asthmatic children were given a second questionnaire, physical examination, medical history review, and auxiliary examination to confirm the diagnosis. Age- and sex-matched non-asthmatic children were randomly recruited to the control group. RESULTS: The number of valid questionnaires was 10 616 (5 444 males and 5 172 females). There were 308 confirmed asthma cases and the overall prevalence was 2.90%. The prevalence in boys was higher than that in girls (3.4% vs 2.4%). The prevalence in children under 3 years of age was 10.2%, which was higher than that in other age groups. The top three triggers for asthma attack in children were respiratory infection (94.2%), weather changes (89.0%), and exercise (35.1%). The most common asthma attack was moderate (71.8%), followed by mild (22.7%). Inhaled corticosteroids, systemic corticosteroids, and antibiotics were applied to 94.8% (292 cases), 74.7% (230 cases), and 90.9% (280 cases) of all patients, respectively. Multivariate logistic regression analysis indicated the following major risk factors for asthma: history of allergic rhinitis (OR=150.285, 95% CI: 31.934-707.264), history of eczema (OR=10.600, 95% CI: 1.054-106.624), history of atopic dermatitis (OR=31.368, 95% CI: 3.339-294.683), food allergies (OR=27.373, 95% CI: 2.670-280.621), method of birth (OR=2.853, 95% CI: 1.311-6.208), age of first antibiotic use (OR=0.384, 95% CI: 0.172-0.857), frequency of antibiotic use within 1 year of age (OR=9.940, 95% CI: 6.246-15.820), use of wall decorating materials (OR=2.108, 95% CI: 1.464-3.036), and use of heat supply in winter (OR=6.046, 95% CI: 1.034-35.362). CONCLUSIONS: The prevalence of childhood asthma is associated with age and gender in Zhengzhou. Most asthma attacks are moderate, often triggered by respiratory infection. Treatment of asthma has been standardized, but still needs further improvement. History of allergic rhinitis, eczema, atopic dermatitis and food allergies, cesarean delivery, frequent use of antibiotics within 1 year of age, use of decorating materials on the wall, and use of heating in winter may increase risk for asthma, and use of antibiotics in older age is a protective factor against asthma in children.