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

Alzheimer’s disease (AD) is a progressive disease that leads to irreversible behavioral changes, erratic emotions, and loss of motor skills. These conditions make people with AD hard or almost impossible to take care of. Multiple internal and external pathological factors may affect or even trigger the initiation and progression of AD. DNA methylation is one of the most effective regulatory roles during AD pathogenesis, and pathological methylation alterations may be potentially different in the various brain structures of people with AD. Although multiple loci associated with AD initiation and progression have been identified, the spatial distribution patterns of AD-associated DNA methylation in the brain have not been clarified. According to the systematic methylation profiles on different structural brain regions, we applied multiple machine learning algorithms to investigate such profiles. First, the profile on each brain region was analyzed by the Boruta feature filtering method. Some important methylation features were extracted and further analyzed by the max-relevance and min-redundancy method, resulting in a feature list. Then, the incremental feature selection method, incorporating some classification algorithms, adopted such list to identify candidate AD-associated loci at methylation with structural specificity, establish a group of quantitative rules for revealing the effects of DNA methylation in various brain regions (i.e., four brain structures) on AD pathogenesis. Furthermore, some efficient classifiers based on essential methylation sites were proposed to identify AD samples. Results revealed that methylation alterations in different brain structures have different contributions to AD pathogenesis. This study further illustrates the complex pathological mechanisms of AD.

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Detecting Brain Structure-Specific Methylation Signatures and Rules for Alzheimer’s Disease

Aging is a fundamental biological process, where key bio-markers interact with each other and synergistically regulate the aging process. Thus aging dysfunction will induce many disorders. Finding aging markers and re-constructing networks based on multi-omics data (i.e. methylation, transcriptional and so on) are informative to study the aging process. However, optimizing the model to predict aging have not been performed systemically, although it is critical to identify potential molecular mechanism of aging related diseases. This paper aims to model the aging self-organization system using a series of supervised learning methods, and study complex molecular mechanisms of aging at system level: i.e. optimizing the aging network; summarizing interactions between aging markers; accumulating patterns of aging markers within module; finding order-parameters in the aging self-organization system. In this work, the normal aging process is modeled based on multi-omics profiles across different tissues. In addition, the computational pipeline aims to model aging self-organizing systems and study the relationship between aging and related diseases (i.e. cancers), thus provide useful indicators of aging related diseases and could help to improve prediction abilities of diagnostics. The aging process could be studied thoroughly by modelling the self-organization system, where key functions and the crosstalk between aging and cancers were identified.

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The self-organization model reveals systematic characteristics of aging

Cancer driver gene is a type of gene with abnormal alterations that initiate or promote tumorigenesis. Driver genes can be used to reveal the fundamental pathological mechanisms of tumorigenesis. These genes may have pathological changes at different omics levels. Thus, identifying cancer driver genes involving two or more omics levels is essential. In this study, a computational investigation was conducted on lung cancer driver genes. Four omics levels, namely, epigenomics, genomics, transcriptomics, and post-transcriptomics, were involved. From the driver genes at each level, the Laplacian heat diffusion algorithm was executed on a protein–protein interaction network for discovering latent driver genes at this level. A following screen procedure was performed to extract essential driver genes, which contained three tests: permutation, association, and function tests, which can exclude false-positive genes and screen essential ones. Finally, the intersection operation was performed to obtain novel driver genes involving two omic levels. The analyses on obtained genes indicated that they were associated with fundamental pathological mechanisms of lung cancer at two corresponding omics levels.

Identification of Novel Lung Cancer Driver Genes Connecting Different Omics Levels With a Heat Diffusion Algorithm

As one of the main characteristics of neoplasia, metabolic reprogramming provides nutrition and energy to enhance cell proliferation and maintain environment homeostasis. Glycolysis is one of the most important components of cancer metabolism and Warburg effect contributes to the competitive advantages of cancer cells in the threatened microenvironment. Studies show strong links between N6-methyladenosine (m6A) modification and metabolic recombination of cancer cells. As the most abundant modification in eukaryotic RNA, m6A methylation plays important roles in regulating RNA processing including splicing, stability, transportation, translation and degradation. The aberration of m6A modification can be observed in a variety of diseases such as diabetes, neurological diseases and cancers. This review describes the mechanisms of m6A on cancer glycolysis and their applications in cancer therapy and prognosis evaluation, aiming to emphasize the importance of targeting m6A on modulating cancer metabolism.

The Role of RNA m6A Modification in Cancer Glycolytic Reprogrammingc.

Pregnancy is a complicated and long procedure during one or more offspring development inside a woman. A short period of oxygen shortage after birth is quite normal for most babies and does not threaten their health. However, if babies have to suffer from a long period of oxygen shortage, then this condition is an indication of pathological fetal intolerance, which probably causes their death. The identification of the pathological fetal intolerance from the physical oxygen shortage is one of the important clinical problems in obstetrics for a long time. The clinical syndromes typically manifest five symptoms that indicate that the baby may suffer from fetal intolerance. At present, liquid biopsy combined with high-throughput sequencing or mass spectrum techniques provides a quick approach to detect real-time alteration in the peripheral blood at multiple levels with the rapid development of molecule sequencing technologies. Gene methylation is functionally correlated with gene expression; thus, the combination of gene methylation and expression information would help in screening out the key regulators for the pathogenesis of fetal intolerance. We combined gene methylation and expression features together and screened out the optimal features, including gene expression or methylation signatures, for fetal intolerance prediction for the first time. In addition, we applied various computational methods to construct a comprehensive computational pipeline to identify the potential biomarkers for fetal intolerance dependent on the liquid biopsy samples. We set up qualitative and quantitative computational models for the prediction for fetal intolerance during pregnancy. Moreover, we provided a new prospective for the detailed pathological mechanism of fetal intolerance. This work can provide a solid foundation for further experimental research and contribute to the application of liquid biopsy in antenatal care.

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Tao Huang

Papers

Detecting Brain Structure-Specific Methylation Signatures and Rules for Alzheimer’s Disease

The self-organization model reveals systematic characteristics of aging

Identification of Novel Lung Cancer Driver Genes Connecting Different Omics Levels With a Heat Diffusion Algorithm

The Role of RNA m6A Modification in Cancer Glycolytic Reprogrammingc.

Investigating gene methylation signatures for fetal intolerance prediction.