FIND:从下一代单端测序数据中快速查找Indel的方法

目的:针对下一代测序数据,尤其是单端测序数据,研究快速、准确查找Indel的方法。方法:先与全基因组参考序列进行快速比对,筛选出包含Indel的序列;再对这些序列进行双向的二次比对,确定Indel长度;最后借助长度信息在锁定范围内查找Indel的确切位置和相关信息。结果:本文成功构建FIND(Fast INDel detection system)系统,用于从单端测序数据中查找Indel信息。以模拟测序数据作为测试数据,在12X测试数据情况下,FIND的灵敏度和特异性分别为87.71%和99.66%,而且该性能还随着测序倍数的增加而提升。结论:充分利用比对过程获取的信息,在确定Indle长度的同时也确定出其大致位置,最终在局部范围内实现对单端测序数据中Indle的快速而准确的查找。     

The new HNO donor, 1-nitrosocyclohexyl acetate, increases contractile force in normal and β-adrenergically desensitized ventricular myocytes

Haplotype, which is the sequence of SNPs in a specific chromosome, plays an important role in disease association studies. However, current sequencing techniques can detect the presence of SNP sites, but they cannot tell which copy of a pair of chromosomes the alleles belong to. Moreover, sequencing errors that occurred in sequencing SNP fragments make it difficult to determine a pair of haplotypes from SNP fragments. To help overcome this difficulty, the haplotype assembly problem is defined from the viewpoint of computation, and several models are suggested to tackle this problem. However, there are no freely available web-based tools to overcome this problem as far as we are aware. In this paper, we present a web-based application based on the genetic algorithm, named HapAssembler, for assembling a pair of haplotypes from SNP fragments. Numerical results on real biological data show that the correct rate of the proposed application in this paper is greater than 95% in most cases. HapAssembler is freely available at http://alex.chonnam.ac.kr/~drminor/hapHome.htm. Users can choose any model among four models for their purpose and determine haplotypes from their input data.     

Pairwise Variable Selection for High‐Dimensional Model‐Based Clustering

Summary Variable selection for clustering is an important and challenging problem in high‐dimensional data analysis. Existing variable selection methods for model‐based clustering select informative variables in a “one‐in‐all‐out” manner; that is, a variable is selected if at least one pair of clusters is separable by this variable and removed if it cannot separate any of the clusters. In many applications, however, it is of interest to further establish exactly which clusters are separable by each informative variable. To address this question, we propose a pairwise variable selection method for high‐dimensional model‐based clustering. The method is based on a new pairwise penalty. Results on simulated and real data show that the new method performs better than alternative approaches that use ?₁ and ?_∞ penalties and offers better interpretation.     

Haplorchis taichui as a Possible Etiologic Agent of Irritable Bowel Syndrome-Like Symptoms

The aim of this study is to clarify the clinical features of Haplorchis taichui infection in humans in Nan Province, Thailand, and to correlate the clinical features with irritable bowel syndrome (IBS)-like symptoms. In this study area, only H. taichui, but neither other minute intestinal flukes nor small liver flukes were endemic. The degree of infection was determined by fecal egg counts and also by collecting adult worms after deworming. The signs and symptoms of individual patients together with their hematological and biochemical laboratory data were gathered to evaluate the relationship between the clinical features and the severity of infection. Special emphasis was made to elucidate the possible similarities of the clinical features of H. taichui infection and IBS-like symptoms. The results showed useful clinical information and the significant (> 50%) proportion of haplorchiasis patients complained of abdominal pain, lassitude, and flatulence, which were the important diagnostic symptoms of IBS. This study has reported a possible link between H. taichui and IBS, and H. taichui might probably play a role in the etiology of these IBS-like symptoms.     

Carbonylated proteins are eliminated during reproduction in C. elegans

Oxidatively damaged proteins accumulate with age in many species (Stadtman (1992) Science 257 , 1220–1224). This means that damage must be reset at the time of reproduction. To visualize this resetting in the roundworm Caenorhabditis elegans, a novel immunofluorescence technique that allows the detection of carbonylated proteins in situ was developed. The application of this technique revealed that carbonylated proteins are eliminated during C. elegans reproduction. This purging occurs abruptly within the germline at the time of oocyte maturation. Surprisingly, the germline was markedly more oxidized than the surrounding somatic tissues. Because distinct mechanisms have been proposed to explain damage elimination in yeast and mice (Aguilaniu et al. (2003) Science 299 , 1751–1753; Hernebring et al. (2006) Proc Natl Acad Sci USA 103 , 7700–7705), possible common mechanisms between worms and one of these systems were tested. The results show that, unlike in yeast (Aguilaniu et al. (2003) Science 299 , 1751–1753; Erjavec et al. (2008) Proc Natl Acad Sci USA 105 , 18764–18769), the elimination of carbonylated proteins in worms does not require the presence of the longevity‐ensuring gene, SIR‐2.1. However, similar to findings in mice (Hernebring et al. (2006) Proc Natl Acad Sci USA 103 , 7700–7705), proteasome activity in the germline is required for the resetting of carbonylated proteins during reproduction in C. elegans. Thus, oxidatively damaged proteins are eliminated during reproduction in worms through the proteasome. This finding suggests that the resetting of damaged proteins during reproduction is conserved, therefore validating the use of C. elegans as a model to study the molecular basis of damage elimination.     

串联质谱图谱从头测序算法研究进展

近年来,基于质谱技术的高通量蛋白质组学研究发展迅速,利用串联质谱图谱鉴定蛋白质是其数据处理中一个基础而又重要的环节．由于不需要利用蛋白质序列数据库,从头测序方法能够分析新物种或者基因组未测序物种的串联质谱数据,具有数据库搜索方法不可替代的优势．简要介绍高通量串联质谱图谱从头测序问题及其研究现状．归纳出几种典型的计算策略并分析了各种策略的优缺点．总结常用的从头测序算法和软件,介绍算法评估的各种指标和常用评估数据集,概括各种算法的特点,展望未来研究可能的发展方向．     

基于多尺度遥感影像分割方法的湿地生态廊道设计

从生物多样性保护的角度,采用多尺度遥感影像分割方法中的人为干扰度模型,计算分割阈值确定湿地生态廊道的宽度,并结合聚类分析法分类的8种人为干扰类型,对建三江地区廊道结构设计进行了研究。结果表明,廊道分割阈值设为20%,非湿地背景噪声为9.43%,湿地生态廊道最佳宽度为1298m。8种人为干扰度中聚类c1、c2、c3和c4类型是受人为干扰较弱的区域,主要分布在浓江、乌苏里江、三江和洪河保护区原始生态环境区域,将其分别设定为核心区、实验区、边缘区、缓冲区4种类型。廊道核心区中的沼泽类型占75%,总体精度高达93.7%,实验区沼泽占72.2%,精度达到75.8%,边缘与缓冲区起到边缘护栏的作用,缓冲区宽度为945m,本研究为湿地生态廊道的建设与修复提供了可靠、科学的参考依据。     

Interaction among Non-toxic Phytoplankton,Toxic Phytoplankton and Zooplankton: Inferences from Field Observations

We explore the mutual dependencies and interactions among different groups of species of the plankton population, based on an analysis of the long-term field observations carried out by our group in the North–West coast of the Bay of Bengal. The plankton community is structured into three groups of species, namely, non-toxic phytoplankton (NTP), toxic phytoplankton (TPP) and zooplankton. To find the pair-wise dependencies among the three groups of plankton, Pearson and partial correlation coefficients are calculated. To explore the simultaneous interaction among all the three groups, a time series analysis is performed. Following an Expectation Maximization (E-M) algorithm, those data points which are missing due to irregularities in sampling are estimated, and with the completed data set a Vector Auto-Regressive (VAR) model is analyzed. The overall analysis demonstrates that toxin-producing phytoplankton play two distinct roles: the inhibition on consumption of toxic substances reduces the abundance of zooplankton, and the toxic materials released by TPP significantly compensate for the competitive disadvantages among phytoplankton species. Our study suggests that the presence of TPP might be a possible cause for the generation of a complex interaction among the large number of phytoplankton and zooplankton species that might be responsible for the prolonged coexistence of the plankton species in a fluctuating biomass.     

A simple genetic algorithm for the optimization of multidomain protein homology models driven by NMR residual dipolar coupling and small angle <Emphasis Type="Italic">X</Emphasis>-ray scattering data

Most proteins comprise several domains and/or participate in functional complexes. Owing to ongoing structural genomic projects, it is likely that it will soon be possible to predict, with reasonable accuracy, the conserved regions of most structural domains. Under these circumstances, it will be important to have methods, based on simple-to-acquire experimental data, that allow to build and refine structures of multi-domain proteins or of protein complexes from homology models of the individual domains/proteins. It has been recently shown that small angle X-ray scattering (SAXS) and NMR residual dipolar coupling (RDC) data can be combined to determine the architecture of such objects when the X-ray structures of the domains are known and can be considered as rigid objects. We developed a simple genetic algorithm to achieve the same goal, but by using homology models of the domains considered as deformable objects. We applied it to two model systems, an S1KH bi-domain of the NusA protein and the γS-crystallin protein. Despite its simplicity our algorithm is able to generate good solutions when driven by SAXS and RDC data.     

A stochastic analysis of actin polymerization in the presence of twinfilin and gelsolin

We develop an efficient stochastic simulation algorithm for analyzing actin filament growth and decay in the presence of various actin-binding proteins. The evolution of nucleotide profiles of filaments can be tracked and the resulting feedback to actin-binding proteins is incorporated. The computational efficiency of the new method enables us to focus on experimentally realistic problems, and as one example we use it to analyze the experimental data of Helfer et al. [(2006). Mammalian twinfilin sequesters ADP-G-actin and caps filament barbed ends: implications in motility. EMBO J. 25, 1184-1195] on the capping and G-actin sequestering activity of twinfilin. We show that the binding specificity of twinfilin for ADP-G-actin is crucial for the observed biphasic evolution of the filament length distribution in the presence of twinfilin, and we demonstrate that twinfilin can be an essential part of the molecular machinery for regulating filament lengths after a short burst of polymerization. Significantly, our simulations indicate that the pyrenyl-actin fluorescence experiments would fail to report the emergence of large filaments under certain experimental conditions.