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

Correlation networks are increasingly being used in bioinformatics applications For example, weighted gene co-expression network analysis is a systems biology method for describing the correlation patterns among genes across microarray samples Weighted correlation network analysis (WGCNA) can be used for finding clusters (modules) of highly correlated genes, for summarizing such clusters using the module eigengene or an intramodular hub gene, for relating modules to one another and to external sample traits (using eigengene network methodology), and for calculating module membership measures Correlation networks facilitate network based gene screening methods that can be used to identify candidate biomarkers or therapeutic targets These methods have been successfully applied in various biological contexts, eg cancer, mouse genetics, yeast genetics, and analysis of brain imaging data While parts of the correlation network methodology have been described in separate publications, there is a need to provide a user-friendly, comprehensive, and consistent software implementation and an accompanying tutorial The WGCNA R software package is a comprehensive collection of R functions for performing various aspects of weighted correlation network analysis The package includes functions for network construction, module detection, gene selection, calculations of topological properties, data simulation, visualization, and interfacing with external software Along with the R package we also present R software tutorials While the methods development was motivated by gene expression data, the underlying data mining approach can be applied to a variety of different settings The WGCNA package provides R functions for weighted correlation network analysis, eg co-expression network analysis of gene expression data The R package along with its source code and additional material are freely available at http://wwwgeneticsuclaedu/labs/horvath/CoexpressionNetwork/Rpackages/WGCNA
 

/pdf/wgcna-an-r-package-for-weighted-correlation-network-analysis-4vjh9rn783.pdf

WGCNA: an R package for weighted correlation network analysis.

The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations. Here we report completion of the project, having reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-genome sequencing, deep exome sequencing, and dense microarray genotyping. We characterized a broad spectrum of genetic variation, in total over 88 million variants (84.7 million single nucleotide polymorphisms (SNPs), 3.6 million short insertions/deletions (indels), and 60,000 structural variants), all phased onto high-quality haplotypes. This resource includes >99% of SNP variants with a frequency of >1% for a variety of ancestries. We describe the distribution of genetic variation across the global sample, and discuss the implications for common disease studies.

https://cdr.lib.unc.edu/downloads/v692t8920

A global reference for human genetic variation.

We describe an object detection system based on mixtures of multiscale deformable part models. Our system is able to represent highly variable object classes and achieves state-of-the-art results in the PASCAL object detection challenges. While deformable part models have become quite popular, their value had not been demonstrated on difficult benchmarks such as the PASCAL data sets. Our system relies on new methods for discriminative training with partially labeled data. We combine a margin-sensitive approach for data-mining hard negative examples with a formalism we call latent SVM. A latent SVM is a reformulation of MI--SVM in terms of latent variables. A latent SVM is semiconvex, and the training problem becomes convex once latent information is specified for the positive examples. This leads to an iterative training algorithm that alternates between fixing latent values for positive examples and optimizing the latent SVM objective function.

/pdf/object-detection-with-discriminatively-trained-part-based-4cnosvuqcp.pdf

Object Detection with Discriminatively Trained Part-Based Models

Probability Distributions.- Linear Models for Regression.- Linear Models for Classification.- Neural Networks.- Kernel Methods.- Sparse Kernel Machines.- Graphical Models.- Mixture Models and EM.- Approximate Inference.- Sampling Methods.- Continuous Latent Variables.- Sequential Data.- Combining Models.

Pattern Recognition and Machine Learning

Whole genome sequencing finds rare high-risk genotypes for hip osteoarthritis in the COMP and CHADL genes

Many practical studies rely on hypothesis testing procedures applied to data sets with missing information. An important part of the analysis is to determine the impact of the missing data on the performance of the test, and this can be done by properly quantifying the relative (to complete data) amount of available information. The problem is directly motivated by applications to studies, such as linkage analyses and haplotype-based association projects, designed to identify genetic contributions to complex diseases. In the genetic studies the relative information measures are needed for the experimental design, technology comparison, interpretation of the data, and for understanding the behavior of some of the inference tools. The central difficulties in constructing such information measures arise from the multiple, and sometimes conflicting, aims in practice. For large samples, we show that a satisfactory, likelihood-based general solution exists by using appropriate forms of the relative Kullback--Leibler information, and that the proposed measures are computationally inexpensive given the maximized likelihoods with the observed data. Two measures are introduced, under the null and alternative hypothesis respectively. We exemplify the measures on data coming from mapping studies on the inflammatory bowel disease and diabetes. For small-sample problems, which appear rather frequently in practice and sometimes in disguised forms (e.g., measuring individual contributions to a large study), the robust Bayesian approach holds great promise, though the choice of a general-purpose "default prior" is a very challenging problem.

Quantifying the Fraction of Missing Information for Hypothesis Testing in Statistical and Genetic Studies

La presente invention concerne des variantes qui predisposent au risque de diabete non insulinodependant, au carcinome basocellulaire, et au cancer du sein. Il est apparu que, quand certaines variantes genetiques sont transmises par un parent, mais pas par l'autre, elles conferent un risque de developper ces maladies. L'invention propose ainsi des procedes de gestion therapeutique, y compris des procedes de diagnostic, faisant reference aux effets de telles origines parentales.

Augustine Kong

Papers

Whole genome sequencing finds rare high-risk genotypes for hip osteoarthritis in the COMP and CHADL genes

Quantifying the Fraction of Missing Information for Hypothesis Testing in Statistical and Genetic Studies

Marqueurs génétiques associés au risque de diabète sucré