抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Data Mining Practical Machine Learning Tools and Techniques

Large-scale reference data sets of human genetic variation are critical for the medical and functional interpretation of DNA sequence changes. Here we describe the aggregation and analysis of high-quality exome (protein-coding region) DNA sequence data for 60,706 individuals of diverse ancestries generated as part of the Exome Aggregation Consortium (ExAC). This catalogue of human genetic diversity contains an average of one variant every eight bases of the exome, and provides direct evidence for the presence of widespread mutational recurrence. We have used this catalogue to calculate objective metrics of pathogenicity for sequence variants, and to identify genes subject to strong selection against various classes of mutation; identifying 3,230 genes with near-complete depletion of predicted protein-truncating variants, with 72% of these genes having no currently established human disease phenotype. Finally, we demonstrate that these data can be used for the efficient filtering of candidate disease-causing variants, and for the discovery of human 'knockout' variants in protein-coding genes.

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Analysis of protein-coding genetic variation in 60,706 humans

I have developed "tennis elbow" from lugging this book around the past four weeks, but it is worth the pain, the effort, and the aspirin. It is also worth the (relatively speaking) bargain price. Including appendixes, this book contains 894 pages of text. The entire panorama of the neural sciences is surveyed and examined, and it is comprehensive in its scope, from genomes to social behaviors. The editors explicitly state that the book is designed as "an introductory text for students of biology, behavior, and medicine," but it is hard to imagine any audience, interested in any fragment of neuroscience at any level of sophistication, that would not enjoy this book. The editors have done a masterful job of weaving together the biologic, the behavioral, and the clinical sciences into a single tapestry in which everyone from the molecular biologist to the practicing psychiatrist can find and appreciate his or

Principles of Neural Science

Enrichment analysis is a popular method for analyzing gene sets generated by genome-wide experiments. Here we present a significant update to one of the tools in this domain called Enrichr. Enrichr currently contains a large collection of diverse gene set libraries available for analysis and download. In total, Enrichr currently contains 180 184 annotated gene sets from 102 gene set libraries. New features have been added to Enrichr including the ability to submit fuzzy sets, upload BED files, improved application programming interface and visualization of the results as clustergrams. Overall, Enrichr is a comprehensive resource for curated gene sets and a search engine that accumulates biological knowledge for further biological discoveries. Enrichr is freely available at: http://amp.pharm.mssm.edu/Enrichr.

Enrichr: a comprehensive gene set enrichment analysis web server 2016 update

CircRNA E3 ubiquitin protein ligase (ITCH) (circRNA ITCH, circ-ITCH), a stable closed-loop RNA derived from the 20q11.22 region of chromosome 20, is a new circRNA discovered in the cytoplasm in recent decades. Studies have shown that it does not encode proteins, but regulates proteins expression at different levels. It is down-regulated in tumor diseases and is involved in a number of biological activities, including inhibiting cell proliferation, migration, invasion, and promoting apoptosis. It can also alter disease progression in non-tumor disease by affecting the cell cycle, inflammatory response, and critical proteins. Circ-ITCH also holds a lot of promise in terms of tumor and non-tumor clinical diagnosis, prognosis, and targeted therapy. As a result, in order to aid clinical research in the hunt for a new strategy for diagnosing and treating human diseases, this study describes the mechanism of circ-ITCH as well as its clinical implications.

https://www.frontiersin.org/articles/10.3389/fgene.2022.927541/pdf

CircRNA ITCH: Insight Into Its Role and Clinical Application Prospect in Tumor and Non-Tumor Diseases

Antifreeze protein (AFP) is a proteinaceous compound with improved antifreeze ability and binding ability to ice to prevent its growth. As a surface-active material, a small number of AFPs have a tremendous influence on the growth of ice. Therefore, identifying novel AFPs is important to understand protein–ice interactions and create novel ice-binding domains. To date, predicting AFPs is difficult due to their low sequence similarity for the ice-binding domain and the lack of common features among different AFPs. Here, a computational engine was developed to predict the features of AFPs and reveal the most important 39 features for AFP identification, such as antifreeze-like/N-acetylneuraminic acid synthase C-terminal, insect AFP motif, C-type lectin-like, and EGF-like domain. With this newly presented computational method, a group of previously confirmed functional AFP motifs was screened out. This study has identified some potential new AFP motifs and contributes to understanding biological antifreeze mechanisms.

Analysis of the Sequence Characteristics of Antifreeze Protein.

Aging is a complex process relating multi-scale omics data. Finding key age markers in normal tissues could help to provide reliable aging predictions in human. However, predicting age based on multi-omics data with both accuracy and informative biological function has not been performed systematically, thus relative cross-tissue analysis has not been investigated entirely, either. Here we have developed an improved prediction pipeline, the Integrating and Stepwise Age-Prediction (ISAP) method, to regress age and find key aging markers effectively. Furthermore, we have performed a serious of network analyses, such as the PPI network, cross-tissue networks and pathway interaction networks. Our results find important coordinated aging patterns between different tissues. Both co-profiling and cross-pathway analyses identify more thorough functions of aging, and could help to find aging markers, pathways and relative aging disease researches.

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Integrative analysis of methylation and transcriptional profiles to predict aging and construct aging specific cross-tissue networks

Background Epidemiological investigations have established unhealthy lifestyles, such as excessive leisurely sedentary behavior (especially TV/television watching) and breakfast skipping, increase the risk of type 2 diabetes (T2D), but the causal relationship is unclear. We aimed to understand how single nucleotide variants contribute to the co-occurrence of unhealthy lifestyles and T2D, thereby providing meaningful insights into disease mechanisms. Methods Combining summary statistics from genome-wide association studies (GWAS) on TV watching (N = 422218), breakfast skipping (N = 193860) and T2D (N = 159208) in European pedigrees, we conducted comprehensive pairwise genetic analysis, including high-definition likelihood (HDL-method), cross-phenotype association studies (CPASSOC), GWAS-eQTL colocalization analysis and transcriptome-wide association studies (TWAS), to understand the genetic overlap between them. We also performed bidirectional two-sample Mendelian randomization (MR) analysis for causal inference using genetic instrumental variables, and two-step MR mediation analysis was used to assess any effects explained by body mass index, lipid traits and glycemic traits. Results HDL-method showed that T2D shared a strong genetic correlation with TV watching (rg = 0.26; P = 1.63×10-29) and skipping breakfast (rg = 0.15; P =2.02×10-6). CPASSOC identifies eight independent SNPs shared between T2D and TV watching, including one novel shared locus. TWAS and CPASSOC showed that shared genes were enriched in lung, esophageal, adipose, and thyroid tissues and highlighted potential shared regulatory pathways for lipoprotein metabolism, pancreatic β-cell function, cellular senescence and multi-mediator factors. MR showed TV watching had a causal effect on T2D (βIVW = 0.629, P IVW = 1.80×10-10), but no significant results were observed between breakfast skipping and T2D. Mediation analysis provided evidence that body mass index, fasting glucose, hemoglobin A1c and high-density lipoprotein are potential factors that mediate the causal relationship between TV and T2D. Conclusions Our findings provide strong evidence of shared genetics and causation between TV watching and T2D and facilitate our identification of common genetic architectures shared between them.

https://www.frontiersin.org/articles/10.3389/fendo.2022.836023/pdf

Shared Genetic Basis and Causal Relationship Between Television Watching, Breakfast Skipping and Type 2 Diabetes: Evidence From a Comprehensive Genetic Analysis

Cervical and anal carcinoma are neoplastic diseases with various intraepithelial neoplasia stages. The underlying mechanisms for cancer initiation and progression have not been fully revealed. DNA methylation has been shown to be aberrantly regulated during tumorigenesis in anal and cervical carcinoma, revealing the important roles of DNA methylation signaling as a biomarker to distinguish cancer stages in clinics. In this research, several machine learning methods were used to analyze the methylation profiles on anal and cervical carcinoma samples, which were divided into three classes representing various stages of tumor progression. Advanced feature selection methods, including Boruta, LASSO, LightGBM, and MCFS, were used to select methylation features that are highly correlated with cancer progression. Some methylation probes including cg01550828 and its corresponding gene RNF168 have been reported to be associated with human papilloma virus-related anal cancer. As for biomarkers for cervical carcinoma, cg27012396 and its functional gene HDAC4 were confirmed to regulate the glycolysis and survival of hypoxic tumor cells in cervical carcinoma. Furthermore, we developed effective classifiers for identifying various tumor stages and derived classification rules that reflect the quantitative impact of methylation on tumorigenesis. The current study identified methylation signals associated with the development of cervical and anal carcinoma at qualitative and quantitative levels using advanced machine learning methods.

/pdf/identifying-anal-and-cervical-tumorigenesis-associated-2pci31v7.pdf

Tao Huang

Papers

CircRNA ITCH: Insight Into Its Role and Clinical Application Prospect in Tumor and Non-Tumor Diseases

Analysis of the Sequence Characteristics of Antifreeze Protein.

Integrative analysis of methylation and transcriptional profiles to predict aging and construct aging specific cross-tissue networks

Shared Genetic Basis and Causal Relationship Between Television Watching, Breakfast Skipping and Type 2 Diabetes: Evidence From a Comprehensive Genetic Analysis

Identifying anal and cervical tumorigenesis-associated methylation signaling with machine learning methods