Self-renewal made simple

Embryonic stem cells (ESCs) are prone to differentiation in culture, suggesting that maintenance of the pluripotent state must be actively induced. In a recent issue of Nature, Ying et al. (2008) use soluble small molecules to inhibit pro-differentiation signals and reveal ESC self-renewal as a default cell fate.     

T-cell development made simple

The thymus is the primary site of T-cell lymphopoiesis. However, the precise molecular interactions that enable the thymus to carry out this function are only recently being elucidated. Although several important molecular players have been identified, including soluble factors, extracellular matrix components, and integral membrane receptors and their ligands, the precise role of these molecules in thymocyte differentiation has yet to be fully characterized. In this regard, the advent of a simple and efficient culture system for the generation of T cells from stem cells, as discussed here, should greatly facilitate the study of T-cell development.     

Quasispecies and recombination

Recombination is introduced into Eigen's theory of quasispecies evolution. Comparing numerical simulations of the rate equations in the non-recombining and recombining cases show that recombination has a strong effect on the error threshold and, for a wide range of mutation rates, gives rise to two stable fixed points in the dynamics. This bi-stability results in the existence of two error thresholds. However, we prove that, for low mutation rates the bi-stability breaks down and the unique equilibrium distribution is concentrated around the sequence with highest fitness.     

PAQ: Partition Analysis of Quasispecies

MOTIVATION: The complexities of genetic data may not be accurately described by any single analytical tool. Phylogenetic analysis is often used to study the genetic relationship among different sequences. Evolutionary models and assumptions are invoked to reconstruct trees that describe the phylogenetic relationship among sequences. Genetic databases are rapidly accumulating large amounts of sequences. Newly acquired sequences, which have not yet been characterized, may require preliminary genetic exploration in order to build models describing the evolutionary relationship among sequences. There are clustering techniques that rely less on models of evolution, and thus may provide nice exploratory tools for identifying genetic similarities. Some of the more commonly used clustering methods perform better when data can be grouped into mutually exclusive groups. Genetic data from viral quasispecies, which consist of closely related variants that differ by small changes, however, may best be partitioned by overlapping groups. RESULTS: We have developed an intuitive exploratory program, Partition Analysis of Quasispecies (PAQ), which utilizes a non-hierarchical technique to partition sequences that are genetically similar. PAQ was used to analyze a data set of human immunodeficiency virus type 1 (HIV-1) envelope sequences isolated from different regions of the brain and another data set consisting of the equine infectious anemia virus (EIAV) regulatory gene rev. Analysis of the HIV-1 data set by PAQ was consistent with phylogenetic analysis of the same data, and the EIAV rev variants were partitioned into two overlapping groups. PAQ provides an additional tool which can be used to glean information from genetic data and can be used in conjunction with other tools to study genetic similarities and genetic evolution of viral quasispecies.     

Viral Quasispecies Assembly via Maximal Clique Enumeration

Virus populations can display high genetic diversity within individual hosts. The intra-host collection of viral haplotypes, called viral quasispecies, is an important determinant of virulence, pathogenesis, and treatment outcome. We present HaploClique, a computational approach to reconstruct the structure of a viral quasispecies from next-generation sequencing data as obtained from bulk sequencing of mixed virus samples. We develop a statistical model for paired-end reads accounting for mutations, insertions, and deletions. Using an iterative maximal clique enumeration approach, read pairs are assembled into haplotypes of increasing length, eventually enabling global haplotype assembly. The performance of our quasispecies assembly method is assessed on simulated data for varying population characteristics and sequencing technology parameters. Owing to its paired-end handling, HaploClique compares favorably to state-of-the-art haplotype inference methods. It can reconstruct error-free full-length haplotypes from low coverage samples and detect large insertions and deletions at low frequencies. We applied HaploClique to sequencing data derived from a clinical hepatitis C virus population of an infected patient and discovered a novel deletion of length 357±167 bp that was validated by two independent long-read sequencing experiments. HaploClique is available at https://github.com/armintoepfer/haploclique. A summary of this paper appears in the proceedings of the RECOMB 2014 conference, April 2-5.     

猪戊肝病毒存在准种现象

为研究猪戊肝病毒准种存在情况,采用逆转录-巢式聚合酶链反应法(RT-nested-PCR)对四株猪戊肝病毒(Hepatitis E virus)第2可读框(ORF2)部分序列进行PCR扩增,将产物克隆后,每个毒株分别随机挑取20个阳性克隆测序,进行DNA序列分析。结果显示4株HEV不同克隆间的ORF2核苷酸序列同源性分别为96.8%~99.7%、98.8%~99.7%、98.8%~99.7%和100%,有变异的克隆核苷酸序列与上海株(SAAS-JDY5)同源性为96.8%~100%。由此证实感染戊肝病毒的猪个体内存在HEV准种。     

慢性丙型肝炎患者中丙型肝炎病毒准种变异研究进展

丙型肝炎病毒（HCV）具有较高的变异性,通常以准种的形式分布在感染者的体内,病毒容易逃离机体的免疫监控,因而无法被有效地清除,导致机体很难控制其感染的发展,故易转变成慢性肝炎。HCV准种变异在宿主体内的持续存在对病毒感染的控制、抗病毒药物和疫苗的发展都是一个巨大的挑战。,我们重点阐述近年来关于HCV准种变异及其与慢性丙型肝炎患者的机体免疫、疾病进展、治疗效果之间关系的研究进展。     

Simulating genetic networks made easy: network construction with simple building blocks

SUMMARY: We present SIM-plex, a genetic network simulator with a very intuitive interface in which a user can easily specify interactions as simple 'if-then' statements. The simulator is based on the mathematical model of Piecewise Linear Differential Equations (PLDEs). With PLDEs, genetic interactions are approximated as acting in a switch-like manner. AVAILABILITY: The Java program, examples and a tutorial are available at http://www.psb.ugent.be/cbd/ CONTACT: {stcru,makui}@psb.ugent.be