基于蛋白质语言模型的突变效应预测研究进展

蛋白质突变效应预测是生物信息学和蛋白质工程领域的一个关键挑战。近年来,深度学习,特别是蛋白质语言模型的发展为该领域带来了新的机遇。本文综述了蛋白质语言模型在蛋白质突变效应预测中的应用,重点讨论了3类主要模型：基于序列的模型、基于结构的模型以及结合序列和结构信息的模型,详细分析了这些模型的原理、优势和局限性,并探讨了无监督学习和监督学习在模型训练中的应用。此外,还讨论了当前面临的主要挑战,包括高质量数据集的获取、数据噪声的处理等。最后,展望了未来研究方向,包括多模态融合、少样本学习等新兴技术的应用前景。本综述为研究者提供了一个全面的视角,以推动蛋白质突变效应预测领域的进一步发展。     

细胞生理代谢网络模型重构和优化的进展

细胞中自发或由酶催化的代谢反应组成了高度复杂的代谢网络,其与细胞生理代谢活动运作密切相关。细胞生理代谢网络模型的重构有助于从系统层面上解析基因型与生长表型之间的关联,为细胞生理代谢活动精准刻画与生物绿色制造等研究提供重要的计算生物学工具。本文系统介绍了全基因组尺度代谢网络模型(genome-scale metabolic models, GEMs)、动力学模型、酶约束代谢模型(enzyme-constrained genome-scale metabolic models, ecGEMs)等不同类型细胞生理代谢网络模型发展与应用的最新研究进展;同时还介绍了GEMs自动化构建研究进展以及条件特异性GEMs建模策略。人工智能技术为高精度细胞生理代谢网络模型构建提供了全新机遇,本文进一步总结了人工智能技术在动力学模型和酶约束模型构建等领域的应用。各类细胞生理代谢网络模型的高质量重构将为今后的定量合成生物学与系统生物学等研究提供强大计算支撑。     

The control of progression order in a captive herd of sable antelope (Hippotragus niger)

A small herd of captive sable antelope (Hippotragus niger) was observed repeatedly while progressing through a gate connecting a pasture to a corral. The ordinal position of each herd member was recorded during each progression. These data were analyzed quantitatively with respect to three models of progression order control and one of random ordering. An end point-control model, stating that the oldest female of a progression occupies the first position while the remainder of the animals randomly distribute themselves within the progression, accounts for the data. These results are related to both protection and resource learning theories of progression order. The terminology used in the study of leadership and ordinal progressions is discussed as well.     

Hierarchical partitioning as an interpretative tool in multivariate inference

Abstract Much of biogeography, conservation and evolutionary biology, and ecology involves very large spatial and temporal extents. Direct manipulation to test hypotheses is usually almost impossible at appropriate scales so that multivariate modelling and especially regression are used to draw causal inferences about which ‘independent’ variables influence the distribution and abundances of species. Such inferences clearly are crucial for the successful management of biological resources and for conserving threatened species. A succession of regression approaches has arisen, many of which yield inconsistent implications. The main problem has been the quest for one (the ‘best’ or the ‘optimal’) regression model from which the impacts of independent variables are inferred. This note is to draw the attention of ecologists to a relatively recent method, hierarchical partitioning, that does not aim to identify a best regression model as such but rather uses all models in a regression hierarchy to distinguish those variables that have high independent correlations with the dependent variable. Such variables are likely to be most influential in controlling variation in the dependent variable. Hierarchical partitioning is not to be regarded as a substitute for experimental manipulation when that is appropriate, but it is likely to produce better deductions than common regression approaches in the many ecological situations in which manipulation is impossible or of doubtful value.     

Analysis of the compliance and the related influence factors in the follow-up process of surveillance for Creutzfeldt-Jakob disease in China

Creutzfeldt-Jakob disease (CJD) is a kind of rare, rapidly progressive fatal central nervous system disorders. In China, the surveillance for CJD has started since 2006. As one of the major issues in CJD surveillance, the follow-up process via telephone plays important role in CJD diagnosis and surveillance. Although the follow-up process was conducted by the experiential staffs from CJD surveillance center in China CDC, it is frequently encountered that some interviewed family members do not cooperate well during follow-up. To screen the possible factors influence on the compliances of the interviewees during CJD follow-up, 11 independent variables from patient aspect and 4 variables from interviewee aspect were selected and a questionnaire was prepared. Based on 199 suspected sporadic CJD cases reported to CJD surveillance center in 2013, a telephone-inquiring was conducted and the degree of compliances of the interviewees were given as good, fair or poor. After screened with univariate analysis and evaluated ordinal logistic regression analysis, several indictors, such as the patient gender, CJD diagnosis, numbers of clinical symptoms, continual medical treatment after diagnosis, medical treatment mode, as well as the relationship with the patient and CJD knowledge of the interviewees, showed influence on the compliance in CJD follow-up process significantly. The data here provide for the first time the factors related with the compliances of the interviewed family members of the suspected CJD patients during follow-up process, which supplies useful clue for us to improve CJD follow-up process and increase the capacity of CJD surveillance.     

Phylogenetic correlates of extinction risk in mammals: species in older lineages are not at greater risk

Phylogenetic information is becoming a recognized basis for evaluating conservation priorities, but associations between extinction risk and properties of a phylogeny such as diversification rates and phylogenetic lineage ages remain unclear. Limited taxon-specific analyses suggest that species in older lineages are at greater risk. We calculate quantitative properties of the mammalian phylogeny and model extinction risk as an ordinal index based on International Union for Conservation of Nature Red List categories. We test for associations between lineage age, clade size, evolutionary distinctiveness and extinction risk for 3308 species of terrestrial mammals. We show no significant global or regional associations, and three significant relationships within taxonomic groups. Extinction risk increases for evolutionarily distinctive primates and decreases with lineage age when lemurs are excluded. Lagomorph species (rabbits, hares and pikas) that have more close relatives are less threatened. We examine the relationship between net diversification rates and extinction risk for 173 genera and find no pattern. We conclude that despite being under-represented in the frequency distribution of lineage ages, species in older, slower evolving and distinct lineages are not more threatened or extinction-prone. Their extinction, however, would represent a disproportionate loss of unique evolutionary history.     

家畜抗性等级性状的QTL定位方法

在广义线性模型的框架内模拟研究了家畜抗性等级性状的QTL定位方法,QTL参数的估计采用最大似然方法,比较了阈模型方法与一般线性方法的QTL定位效率,并对影响等级性状QTL定位效率的主要因素（QTL效应、性状的遗传力）进行了模拟研究,实验设计为多个家系的女儿设计,资源群体大小为500头。研究结果表明：在QTL位置参数估计及检验功效方面,阈模型方法具有一定的优势,对抗性等级性状QTL定位的功效也高于线性方法。另外,性状遗传力和QTL效应的大小对QTL定位的准确度也有直接的影响,随着性状遗传力QTL效应的