基因组学相关概念及其研究进展

２０世纪以来,生命科学得到了空前的发展,大量新的概念不断涌现并相应产生了许多新兴学科,本文试图对当今研究的热点领域－基因组学,包括结构基因组学,比较基因组学,功能基因组学和较新兴的蛋白质组学、功能蛋白质组学及其相关概念、营养基因组学、生物信息学及其相关概念和近期进展做一介绍。     

从结构基因组学到功能基因组学

基因组学研究随着模式生物基因组全序列测定的完成由结构基因组学阶段发展到功能基因组学阶段,基因组学成为当今最为活跃、最有影响的前沿学科.以结构基因组学的研究成果为基础,功能基因组学中各学科因其原理不同及其关键技术的特点和优势,具有各自的应用范畴和发展趋势.功能基因组学不断渗透入现代科学的各领域,促成了适用于不同研究目的新兴学科的诞生.     

功能基因组学研究概述

21世纪是生物时代和信息时代,基因组学的研究已从结构基因组学转向功能基因组学,功能基因组学时代对于基因功能的研究也由单一基因转向大规模、批量分析。对功能基因组学及相关学科的概念作了概述,综述了功能基因组学的研究内容与方法,主要包括应用差异显示反转录PCR、基因表达序列分析（SAGE）、微点阵、蛋白质组学和生物信息学等方法来研究基因组表达概况、基因组多样性和模式生物学等。     

小麦的比较基因组学和功能基因组学

小麦是异源多倍体植物,具有大的染色体组,并且基因组中重复序列所占比例较高,这些特征限制了小麦基因组研究的进展。比较基因组学方法为运用模式植物进行小麦基因组学研究提供了一个操作平台。功能基因组学的研究集中于基因组中转录表达的部分,基因功能的确定是功能基因组学研究的主要内容。对比较基因组学在小麦基因组研究中的应用和小麦功能基因组学的研究内容和方法进行了综述。     

林木基因组学研究进展

林木基因组学研究进展迅速。结构基因组学方面,已构建了近40个主要造林树种的遗传连锁图谱,在不同树种中定位了30余个重要的数量性状位点,在部分树种中开展了基因组比较和综合图谱构建研究,杨树的全基因组测序已经完成,桉树的全基因组测序正在进行。功能基因组学方面,已分析了主要造林树种多种组织的转录组EST序列,对林木次生生长与木材形成、开花和抗寒性的形成等过程开展了功能基因组学研究。另外,探讨了林木基因组学研究的发展趋势,以期为我国林木基因组学研究提供有益的参考。     

人类基因组计划的机遇和挑战：Ⅰ.从结构基因组学到功能基因组学

人类基因组计划的机遇和挑战：Ⅰ．从结构基因组学到功能基因组学陈竺＊李伟俞曼熊慧陈赛娟（上海第二医科大学附属瑞金医院、血液学研究所、卫生部暨上海市人类基因组研究重点实验室＊上海人类基因组研究中心、上海生命科学研究中心）关键词人类基因组计划结构基因组学功...     

嗜酸氧化亚铁硫杆菌基因组学研究进展

嗜酸氧化亚铁硫杆菌(Acidithiobacillus ferrooxidan,A.ferrooxidans)广泛存在于酸性矿物废水中,与生物冶金和环境净化紧密相关。不同来源嗜酸氧化亚铁硫杆菌全基因组的测序,为我们利用比较基因组学和功能基因组学的方法去洞察嗜酸氧化亚铁硫杆菌功能基因,提供了坚实的研究基础和丰富的科研信息。简述了嗜酸氧化亚铁硫杆菌基因组学的基本特征;从比较基因组学和功能基因组学发现了嗜酸氧化亚铁硫杆菌菌株基因组水平的差异;通过生物信息学概述了该菌的铁和硫代谢机制,并从细菌的功能基因组学对其在生物冶金与环境治理等应用进行了展望。     

科学出版社精品图书

基因IX（原版书）,比较基因组学,Brock微生物生物学（原书第十版,影印）,功能基因组学,英汉生物化学及分子生物学词典（第二版）.[编者按]     

植物功能基因组学研究进展

植物功能基因组学是从整体水平研究基因的功能及表达规律的科学。对植物功能基因组学的研究将助于我们对基因功能的理解和对植物性状的定性改造和利用。本文简要介绍了植物功能基因组学的概念、研究方法和最新研究进展。     

影像基因组学分析方法研究进展

在生物医学大数据背景下,精准医学的研究重点之一是基因型数据和表型数据的融合及关联分析,通过数据融合及关联分析,认识疾病表型特征与基因多态性及基因活动之间的关系。影像基因组学作为一个新兴研究领域,它将疾病影像数据和基因组数据整合,并挖掘两者之间的联系,从而发现能够反映基因多态或表达的影像特征,在此基础上建立基于影像特征的非侵入式疾病诊断方法,是目前生物医学最有前景的研究领域之一。综述了影像基因组学领域的研究方法,包括基因组数据分析、影像数据分析以及基因组数据-影像数据融合分析方法。在此基础上,介绍了影像基因组学目前在临床上的典型应用,包括疾病的辅助诊断、预后预测和疗效评估。最后,对影像基因组学的未来发展进行了展望。     

Simple sequential boundaries for treatment selection in multi-armed randomized clinical trials with a control

Summary .   In situations when many regimens are possible candidates for a large phase III study, but too few resources are available to evaluate each relative to the standard, conducting a multi-armed randomized selection trial is a useful strategy to remove inferior treatments from further consideration. When the study has a relatively quick endpoint such as an imaging-based lesion volume change in acute stroke patients, frequent interim monitoring of the trial is ethically and practically appealing to clinicians. In this article, I propose a class of sequential selection boundaries for multi-armed clinical trials, in which the objective is to select a treatment with a clinically significant improvement upon the control group, or to declare futility if no such treatment exists. The proposed boundaries are easy to implement in a blinded fashion, and can be applied on a flexible monitoring schedule in terms of calendar time. Design calibration with respect to prespecified levels of confidence is simple, and can be accomplished when the response rate of the control group is known only up to an interval. One of the proposed methods is applied to redesign a selection trial with an imaging endpoint in acute stroke patients, and is compared to an optimal two-stage design via simulations: The proposed method imposes smaller sample size on average than the two-stage design; this advantage is substantial when there is in fact a superior treatment to the control group.     

最优化设计连续的自然保护区

生境破碎是导致生物多样性损失的重要原因之一,避免生境破碎的一个有效方式是建立连续的自然保护区使物种可在保护区内自由移动。不加选择地把大片土地都转为保护区是实现连续的一个途径,但资源是有限的,应当以最优的方式分配。如何最优化设计生态上和经济上都有效的保护区成为生物保护领域一个重要议题。从一组备选地块中选择一部分组成自然保护区,这样的问题主要有两种解法:启发式方法和最优化方法。启发式方法虽然灵活且运算速度快但不能保证最优解因而可能导致稀缺资源的浪费,最优化方法保证得到的解是最优的但建模和运算存在困难。建立一个线性整数规划模型用于设计一个最小的连续保护区,用Dantzig剪切法消除循环确保形成一个连续的树,对应一个连续的保护区,检验了模型的计算效率。结果显示,模型可在合理时间内解决一个包含100个备选地块和30个物种的连续保护区设计问题,计算效率显著优于同类目的的其它方法。以美国伊利诺伊州Cache河流域11种濒危鸟类的保护区设计为例说明了该方法的应用,设计了两种情况下连续的保护区。讨论了模型的局限和数据问题。     

江苏泗洪下草湾中中新世脊椎动物群——6.鸟纲

本文记述了近年来在江苏泗洪下草湾组中补采到的6种鸟类,其中包括天岗琵鹭 Platalea tiangangensis sp. nov.和松林庄古石鸡 Palaeoalectoris songlinensis gen. et sp. nov.,前者系琵鹭属迄今最早的记录,后者为雉科鹑族目前已知最早的成员.     

The effect of gene flow on the coalescent time in the human-chimpanzee ancestral population

The coalescent process in the human-chimpanzee ancestral population is investigated using a model, which incorporates a certain time period of gene flow during the speciation process. a is a parameter to represent the degree and time of gene flow, and the model is identical to the null model with an instantaneous species split when a=infinity. A maximum likelihood (ML) method is developed to estimate a, and its power and reliability is investigated by coalescent simulations. The ML method is applied to nucleotide divergence data between human and chimpanzee. It is found that the null model with an instantaneous species split explains the data best, and no strong evidence for gene flow is detected. The result is discussed in the view of the mode of speciation. Another ML method is developed to estimate the male-female ratio (alpha) of mutation rate, in which the coalescent process in the ancestral population is taken into account.     

Tumor suppressive maspin and epithelial homeostasis

Maspin is a 42-kDa novel serine protease inhibitor (serpin) with multifaceted tumor suppressive activities. To date, the consensus that maspin expression predicts a better prognosis still largely holds for breast, prostate, colon, and oral squamous cancers. Interestingly, however, more detailed analyses revealed a biphasic expression pattern of maspin in early steps of tumorigenicity and re-expression of maspin in dormant cancer metastatic revertants. These data suggest a sensitivity of maspin expression to changes of epithelial microenvironments, and a role of maspin in epithelial homeostasis. Experimental evidence consistently showed that maspin suppresses tumor growth, invasion and metastasis, induces tumor redifferentiation, and enhances tumor cell sensitivity to apoptosis. Maspin protein isolated from biological sources is a monomer, which is present as a secreted, a cytoplasmic, a nuclear, as well as a cell surface-associated protein. Nuclear maspin is associated with better prognoses of cancer. It is further noted that extracellular maspin is sufficient to block tumor induced extracellular matrix degradation, tumor cell motility and invasion, whereas intracellular maspin is responsible for the increased cellular sensitivity to apoptosis. Despite these exciting developments, the mechanistic studies of maspin have proven challenging primarily due to the lack of a prototype molecular model. Although the maspin sequence has overall homologies with other members in the serpin superfamily, it does not behave like a typical serpin, that is, non-inhibitory toward active serine proteases in solution. This novel feature is in line with the X-ray crystallographic evidence. Several recent studies dedicated to finding the maspin partners support a paradigm shift. The current review is intended to summarize these recent findings and discuss a new perspective of maspin in epithelial homeostasis.     

Logical Probability and Risk Assessment

A risk assessment is intended to provide a statement of current knowledge which is intended to inform a decision-maker of the current state of knowledge in response to a particular concern. Because answering the concerns of decision-makers often requires inferences to be drawn, doubt often arises over how the inference is to be drawn. In quantitative risk assessment, where a mathematical equation or model is used to draw the inference, this uncertainty is referred to as model uncertainty. A two-step process, which is referred to as logical probability, is proposed as a technique for representing model uncertainty in a risk assessment. The first step involves assigning model weights in which the degree of evidential support for each of the alternative models is considered. The second step involves assigning a unique interval in the range of 0 to 1 for each model which reflects the models' weight, to form a probability distribution. While the second step is straightforward, the first step is not. Assigning model weights requires consideration of any line of evidence that may reasonably impact the validity of the assertion of a model. While the development of a procedure for doing so may be expected to be a process which reflects the subjective preferences of whomever is involved in creating it, there are some historical precedents on which to build. Foremost among these are (1) the use of a correlation coefficient or other goodness-of-fit criteria to measure the degree of correspondence between a given model and a set of observations which are used as evidence to support it, and (2) preference given to models which are simpler, which may be ascertained as the number of adjustable parameters the model contains. Additional principles, which have little or no tradition to stand on, must be used to reflect the impact of other empirically supported beliefs on model preference. The procedure proposed is comparable to the procedure known as decision analysis, in which probabilities are assigned to alternative models based on expert or subjective input. The principal difference in the present case is that it is suggested that principles which transcend the decision at hand should be sought and articulated in order to generate a consistent measure of uncertainty arising from interpretation.     

Physical factors that affect the number and size of Golgi cisternae

Despite continual membrane reorganization in the Golgi complex, the number of cisternae in a Golgi stack is a stable parameter. The cisternal number is conserved within any given cell line and also after Golgi reassembly, e.g. following brefeldin-A-induced disruption. However, the factors that determine the cisternal number in a single Golgi stack remain to be fully determined. We propose a simple mechanical model of the Golgi stack and present a theoretical analysis of different physical factors that may affect the number of cisternae in a Golgi stack. The model takes into account the Golgi membrane bending elasticity, which is related to the membrane curvature, and the adhesion, which holds the cisternae together. The analysis shows that the equilibrium configuration of the Golgi stack can be regarded as a balance between these two effects - the adhesion, which tends to increase the number of cisternae, is opposed by the membrane resistance to bending, which does not favor highly curved cisternal rims. The adhesion strength that is needed to hold together a typical stack is calculated. In addition, the model is used to analyze changes in the cisternal numbers as a controlled traffic wave enters a Golgi stack and increases the amount of the membrane in that stack.     

Measurement of leaf biomechanical properties in studies of herbivory: Opportunities,problems and procedures

Leaf biomechanical properties have the potential to act as antiherbivore defences. However, compared with studies on chemical defences, there are few studies that have demonstrated that the physical or biomechanical structure of plants can prevent or influence herbivory. This difference in focus by ecologists may relate to the dominant paradigm of plant chemical defences in ecological research and the perceived difficulties that ecologists have with the engineering principles embedded in biomechanics. The advantage of using materials engineering concepts is that each property is precisely defined and quantifiable, although the latter may be difficult in leaves because of their composite and anisotropic nature. Most herbivory studies have used simple penetrometers to measure leaf properties, often termed ‘toughness’. As defined in materials engineering, the measured properties are ‘force to fracture’ and ‘strength’, not toughness. Measurement of strength, the resistance to crack initiation, is relevant to understanding herbivory. Measurement of ‘toughness’ as defined by materials engineering is also relevant. Toughness is the resistance to crack propagation and is a measure of the energy required to fracture the leaf. This requires more sophisticated equipment than simple penetrometers because it requires a simultaneous measure of the punch displacement. In addition, purists would argue that a punch cannot be used to measure true toughness because the crack is not controlled and plastic deformation is also involved. However, it may be the only method that allows detection of fine‐scale pattern in mechanical properties across a leaf surface at a scale that is relevant to herbivory. There is very little work on the scale at which these properties vary, particularly with regard to different sized herbivores. In addition, few studies have investigated a broad range of relevant biomechanical properties in relation to herbivory. Therefore, it is not possible yet to be definitive about the relative merits of the various types of tests. A single test might show a pattern in relation to herbivore damage at a gross level. However, to really understand the functional and ecological significance of leaf texture in relation to herbivory, a more reductionist approach is needed. Only then can we move on to the larger scales of pattern that many ecologists are seeking.     

A Bayesian approach to joint modeling of matrix-valued imaging data and treatment outcome with applications to depression studies

In this paper, we propose a unified Bayesian joint modeling framework for studying association between a binary treatment outcome and a baseline matrix-valued predictor. Specifically, a joint modeling approach relating an outcome to a matrix-valued predictor through a probabilistic formulation of multilinear principal component analysis is developed. This framework establishes a theoretical relationship between the outcome and the matrix-valued predictor, although the predictor is not explicitly expressed in the model. Simulation studies are provided showing that the proposed method is superior or competitive to other methods, such as a two-stage approach and a classical principal component regression in terms of both prediction accuracy and estimation of association; its advantage is most notable when the sample size is small and the dimensionality in the imaging covariate is large. Finally, our proposed joint modeling approach is shown to be a very promising tool in an application exploring the association between baseline electroencephalography data and a favorable response to treatment in a depression treatment study by achieving a substantial improvement in prediction accuracy in comparison to competing methods.     

Predicting adaptation of phenology in response to climate change, an insect herbivore example

Climate change has led to an advance in phenology in many species. Synchrony in phenology between different species within a food chain may be disrupted if an increase in temperature affects the phenology of the different species differently, as is the case in the winter moth egg hatch–oak bud burst system. Operophtera brumata (winter moth) egg hatch date has advanced more than Quercus robur (pedunculate oak) bud burst date over the past two decades. Disrupted synchrony will lead to selection, and a response in phenology to this selection may lead to species genetically adapting to their changing environment. However, a prerequisite for such genetic change is that there is sufficient genetic variation and severe enough fitness consequences. So far, examples of observed genetic change have been few. Using a half-sib design, we demonstrate here that O. brumata egg-hatching reaction norm is heritable, and that genetic variation exists. Fitness consequences of even a few days difference between egg hatch and tree bud opening are severe, as we experimentally determined. Estimates of genetic variation and of fitness were then combined with a climate scenario to predict the rate and the amount of change in the eggs' response to temperature. We predict a rapid response to selection, leading to a restoration of synchrony of egg hatch with Q. robur bud opening. This study shows that in this case there is a clear potential to adapt – rapidly – to environmental change. The current observed asynchrony is therefore not due to a lack of genetic variation and at present it is unclear what is constraining O. brumata to adapt. This kind of model may be particularly useful in gaining insight in the predicted amount and rate of change due to environmental changes, given a certain genetic variation and selection pressure.