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.

/pdf/analysis-of-protein-coding-genetic-variation-in-60-706-43wjw7d23z.pdf

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

Cardiorespiratory fitness (CRF) and endurance performance are characterized by a complex genetic trait with high heritability. Although research has identified many physiological and environmental correlates with CRF, the genetic architecture contributing to CRF remains unclear, especially in non-athlete population. A total of 762 Chinese young female participants were recruited and an endurance run test was used to determine CRF. We used a fixed model of genome-wide association studies (GWAS) for CRF. Genotyping was performed using the Affymetrix Axiom and illumina 1 M arrays. After quality control and imputation, a linear regression-based association analysis was conducted using a total of 5,149,327 variants. Four loci associated with CRF were identified to reach genome-wide significance (P < 5.0 × 10-8), which located in 15q21.3 (rs17240160, P = 1.73 × 10-9, GCOM1), 3q25.31 (rs819865, P = 8.56 × 10-9, GMPS), 21q22.3 (rs117828698, P = 9.59 × 10-9, COL18A1), and 17q24.2 (rs79806428, P = 3.85 × 10-8, PRKCA). These loci (GCOM1, GMPS, COL18A1 and PRKCA) associated with cardiorespiratory fitness and endurance performance in Chinese non-athlete young females. Our results suggest that these gene polymorphisms provide further genetic evidence for the polygenetic nature of cardiorespiratory endurance and be used as genetic biomarkers for future research.

/pdf/four-loci-are-associated-with-cardiorespiratory-fitness-and-4mhgnwhzgx.pdf

Four Loci Are Associated with Cardiorespiratory Fitness and Endurance Performance in Young Chinese Females.

Non-coding RNAs have been shown to play important regulatory roles, notably in cancer development. In this study, we investigated the role of microRNAs and circular RNAs in Nasopharyngeal Carcinoma (NPC) by constructing a circRNA-miRNA-mRNA co-expression network and performing differential expression analysis on mRNAs, miRNAs, and circRNAs. Specifically, the Epstein-Barr virus (EBV) infection has been found to be an important risk factor for NPC, and potential pathological differences may exist for EBV+ and EBV- subtypes of NPC. By comparing the expression profile of non-cancerous immortalized nasopharyngeal epithelial cell line and NPC cell lines, we identified differentially expressed coding and non-coding RNAs across three groups of comparison: cancer vs. non-cancer, EBV+ vs. EBV- NPC, and metastatic vs. non-metastatic NPC. We constructed a ceRNA network composed of mRNAs, miRNAs, and circRNAs, leveraging co-expression and miRNA target prediction tools. Within the network, we identified the regulatory ceRNAs of CDKN1B, ZNF302, ZNF268, and RPGR. These differentially expressed axis, along with other miRNA-circRNA pairs we identified through our analysis, helps elucidate the genetic and epigenetic changes central to NPC progression, and the differences between EBV+ and EBV- NPC.

Competitive Endogenous RNA Landscape in Epstein-Barr Virus Associated Nasopharyngeal Carcinoma.

Prediction of Enzyme’s Family Based on Protein-Protein Interaction Network

Lung cancer, the most common of malignant tumors, are typically of the non-small cell (NSCLC) type. T-cell based immunotherapies are a promising and powerful approach to treating NSCLCs. To characterize the CD8+ T cells of non-small cell lung cancer, we re-analyzed the published RNA-Seq gene expression profiles of 36 CD8+ T cell isolated from tumor (TIL) samples and 32 adjacent uninvolved lung (NTIL) samples. With an advanced Monte-Carlo method of feature selection, we identified the CD8+ TIL specific expression patterns. These patterns revealed the key dysfunctional genes and pathways in CD8+ TIL and shed light on the molecular mechanisms of immunity and use of immunotherapy.

/pdf/identification-and-analysis-of-dysfunctional-genes-and-rtr2flvl1p.pdf

Identification and Analysis of Dysfunctional Genes and Pathways in CD8+ T Cells of Non-Small Cell Lung Cancer Based on RNA Sequencing.

Osteoarthritis is one of the most prevalent chronic joint diseases for middle-aged and elderly people. But in recent years, the number of young people suffering from the disease increases quickly. It is known that osteoarthritis is a common degenerative disease caused by the combination and interaction of many factors such as natural and environmental factors. DNA methylations reflect the effects of environmental factors. Several researches on DNA methylation at specific genes in OA cartilage indicated the great potential roles of DNA methylation in OA. To systematically investigate the methylation pattern in knee and hip osteoarthritis, we analyzed the methylation profiles in cartilage of 16 OA hip samples, 19 control hip samples and 62 OA knee samples. 12 discriminative methylation sites were identified using advanced minimal Redundancy Maximal Relevance (mRMR) and Incremental Feature Selection (IFS) methods. The SVM classifier of these 12 methylation sites from genes like MEIS1, GABRG3, RXRA, and EN1, can perfectly classify the OA hip samples, control hip samples and OA knee samples evaluated with LOOCV (Leave-One Out-Cross Validation). These 12 methylation sites can not only serve as biomarker, but also provide underlying mechanism of OA.

/pdf/the-methylation-pattern-for-knee-and-hip-osteoarthritis-rzrmv8umop.pdf

Tao Huang

Papers

Four Loci Are Associated with Cardiorespiratory Fitness and Endurance Performance in Young Chinese Females.

Competitive Endogenous RNA Landscape in Epstein-Barr Virus Associated Nasopharyngeal Carcinoma.

Prediction of Enzyme’s Family Based on Protein-Protein Interaction Network

Identification and Analysis of Dysfunctional Genes and Pathways in CD8+ T Cells of Non-Small Cell Lung Cancer Based on RNA Sequencing.

The Methylation Pattern for Knee and Hip Osteoarthritis.