人重组磷脂酶D_2变构体cDNA和蛋白质序列分析

采用VectorNTI、DNATools等计算机分析软件及信息库,研究人重组磷脂酶D2(rhPLD2)变构体的生物学特征。rhPLD2具有多种基因结构和功能调控元件,其编码的蛋白质具有发挥功能所必需的活性保守基序和一定的空间结构,表明rhPLD2应是一种具有一定生物学功能的异质性蛋白质。     

The cortical column, a new processing unit for cortex-like networks

We propose in this paper a new connectionnist model which is the result of a collaboration between computer science and neurobiology researchers. This model is based upon a cortical-like network close to cortical function simulation. We present its functional and architectural characteristics together with the very encouraging results obtained for the first simulations on the visual and auditory cortical functions in speech and character recognition.     

机器学习在蛋白质功能预测领域的研究进展

蛋白质是有机生命体内不可或缺的化合物,在生命活动中发挥着多种重要作用,了解蛋白质的功能有助于医学和药物研发等领域的研究。此外,酶在绿色合成中的应用一直备受人们关注,但是由于酶的种类和功能多种多样,获取特定功能酶的成本高昂,限制了其进一步的应用。目前,蛋白质的具体功能主要通过实验表征确定,该方法实验工作繁琐且耗时耗力,同时,随着生物信息学和测序技术的高速发展,已测序得到的蛋白质序列数量远大于功能获得注释的序列数量,高效预测蛋白质功能变得至关重要。随着计算机技术的蓬勃发展,由数据驱动的机器学习方法已成为应对这些挑战的有效解决方案。本文对蛋白质功能及其注释方法以及机器学习的发展历程和操作流程进行了概述,聚焦于机器学习在酶功能预测领域的应用,对未来人工智能辅助蛋白质功能高效研究的发展方向提出了展望。     

Aqueous Hydration of Nucleic Acid Constituents: Monte Carlo Computer Simulation Studies

Abstract

Monte Carlo computer simulations were performed on dilute aqueous solutions of thymine, cytosine, uracil, adenine, guanine, the dimethyl phosphate anion in the gauche-gauche conformation and a ribose and deoxyribose derivative. The aqueous hydration of each molecule was analysed in terms of quasi-component distribution functions based on the Proximity Criterion, and partitioned into hydrophobic, hydrophilic and ionic contributions. Color stereo views of selected hydration complexes are also presented. A preliminary discussion of the transferability of functional group coordination numbers is given. The results enable to comment on two current problems related to the hydration of nucleic acids: a) the theory of Dickerson and coworkers on the role of water in the relative stability of the A and B forms of DNA and b) the idea of water bridges and filaments emerging from the computer simulation results on the hydration of DNA fragments by Clementi.     

我国四株狂犬病毒M和P基因序列分析和所编码蛋白的分析

为了解我国狂犬病毒M、P基因序列和结构特点,用RT-PCR方法获得目的基因片段,测定核苷酸序列后,计算机分析核苷酸和氨基酸序列及其功能区位点结构。结果显示四株病毒M基因核苷酸和氨基酸序列同源性分别为83.9%～99.5%和93.1%～99%,四株狂犬病毒M蛋白上调节病毒RNA转录和复制功能的第58位氨基酸残基均为谷氨酰胺残基(E),与特异性细胞蛋白WW区域作用的PPxY结构序列均为PPEY保守序列;四株病毒P基因核苷酸和氨基酸序列同源性分别为83.6%～99.8%和87.2%～99%,P蛋白与胞浆动力蛋白轻链LC8相互作用的序列位于143～148位氨基酸残基,均为DKSTQT,四株病毒P基因与L蛋白、N蛋白作用位点序列显示未发生影响其生物学功能的变异。研究结果证实了这两种蛋白结构在病毒致病性中起重要作用的推论。     

A program for least squares analysis of reassociation and hybridization data.

A computer program is described for the rapid calculation of least squares solutions for data fitted to different functions normally used in reassociation and hybridization kinetic measurements. The equations for the fraction not reacted as a function of Cot follow: First order, exp(-kCot); second order, (1+kCot)-1; variable order, (1+kCot)-n; approximate fraction of DNA sequence remaining single stranded, (1+kCot)-.44; and a function describing the pairing of tracer when the rate constant for the tracer (k) is distinct from the driver rate constant (kd): (formula: see text). Several components may be used for most of these functional forms. The standard deviations of the individual parameters at the solutions are calculated.     

Is the cerebellum involved in learning and cognition?

Current studies are examining whether the cerebellum has a functional role in non-motor tasks using both behavioral and physiological methods with animals, and computer simulations of a classical conditioning task. Cerebellar involvement in cognition has been assessed in studies with healthy and neurologically impaired humans. The results have led to new hypotheses that are providing testable predictions about the role of the cerebellum in perception, attention, and other cognitive functions.     

Local false discovery rate facilitates comparison of different microarray experiments

The local false discovery rate (LFDR) estimates the probability of falsely identifying specific genes with changes in expression. In computer simulations, LFDR <10% successfully identified genes with changes in expression, while LFDR >90% identified genes without changes. We used LFDR to compare different microarray experiments quantitatively: (i) Venn diagrams of genes with and without changes in expression, (ii) scatter plots of the genes, (iii) correlation coefficients in the scatter plots and (iv) distributions of gene function. To illustrate, we compared three methods for pre-processing microarray data. Correlations between methods were high (r = 0.84–0.92). However, responses were often different in magnitude, and sometimes discordant, even though the methods used the same raw data. LFDR complements functional assessments like gene set enrichment analysis. To illustrate, we compared responses to ultraviolet radiation (UV), ionizing radiation (IR) and tobacco smoke. Compared to unresponsive genes, genes responsive to both UV and IR were enriched for cell cycle, mitosis, and DNA repair functions. Genes responsive to UV but not IR were depleted for cell adhesion functions. Genes responsive to tobacco smoke were enriched for detoxification functions. Thus, LFDR reveals differences and similarities among experiments.     

Effect of computer work on the state of physiological functions in children aged 7 to 10 years

We studied the age- and sex-related functional characteristics of the central nervous system (CNS), cardiovascular system (CVS), lability of the visual sensory system, and mental capacity before and after a continuous computer work for 15 min in children aged 7, 8, 9, and 10 years. The results of the research showed that the resistance of the physiological systems of the body to loads associated with computer work increases in primary school children with age. We also observed sex-related differences: many parameters of functional performance during computer work at the age of 8 years were better in girls than in boys, which was due to a higher rate of development; at the age of 10 years, girls had a larger number of adverse changes in the functional state of the body compared with boys, which is possibly due to the onset of puberty.     

Analysis of hexamer and pentamer motifs within a maize database: the presence of motif ‘signatures’ in functional gene categories

Several transposable elements (TEs) have been reported in association with genes in maize and other plants. In this study we found, based on statistical analyses of 951 DNA sequences within a maize computer database, that short hexamer and pentamer DNA motifs from the Activator (Ac) and from the Tourist TEs, respectively, were also associated with maize genes. Moreover, these two short hexamer and pentamer TE motifs were nonrandomly and nearly nonrandomly distributed, respectively, with respect to particular biochemical functions of those maize genes. To determine whether this distribution may be unique to TE motifs, or may be more widespread among hexamers/pentamers in general, we similarly studied six additional hexamer or pentamer sequences not derived from TEs. These also showed nonrandom distribution with respect to functional gene categories in the maize database. However, each of the total of eight short sequence motifs we studied differed in its pattern of association with distinct sets of functional gene categories; that is, there was a unique ‘signature’ for each of the hexamers and pentameters tested. Potential biological hypotheses to explain these findings are discussed. This revised version was published online in July 2006 with corrections to the Cover Date.     

Some Formal Approaches to the Analysis of Kinetic Data in Terms of Linear Compartmental Systems

A formal approach to the routine analysis of kinetic data in terms of linear compartmental systems is presented. The methods of analysis are general in that they include much of the theory in common use, such as direct solution of differential equations, integral equations, transfer functions, fitting of data to sums of exponentials, matrix solutions, etc. The key to the formalism presented lies in the fact that a basic operational unit—called “compartment”—has been defined, in terms of which physical and mathematical models as well as input and output functions can be expressed. Additional features for calculating linear combinations of functions and for setting linear dependence relations between parameters add to the versatility of this method. The actual computations for the values of model parameters to yield a least squares fit of the data are performed on a digital computer. A general computer program was developed that permits the routine fitting of data and the evolution of models.     

Antimicrobial and other oligopeptides of grapes

Structures and functions of about 700 oligopeptides of various plants are presently known. However, only one polypeptide has been isolated from grapes and characterized. At the same time, tens of thousands of uncharacterized amino acid sequences have been revealed in this plant, among which there can also be precursors of oligopeptide regulators. Due to the scientific and practical importance of innate immunity of agricultural plants, we have undertaken structural and functional investigation of these sequences to identify new regulatory oligopeptides including antimicrobial agents. For this purpose, we elaborated a special method of computer analysis enabling comparison of primary structures of putative precursors of grape oligopeptides with amino acid sequences of known oligopeptides of other plants. Structural similarity served as the basis for prediction of potential functional properties. As a result, over 20 new structures of antimicrobial and other grape oligopeptides have been found.     

Non-Invasive Brain-to-Brain Interface (BBI): Establishing Functional Links between Two Brains

Transcranial focused ultrasound (FUS) is capable of modulating the neural activity of specific brain regions, with a potential role as a non-invasive computer-to-brain interface (CBI). In conjunction with the use of brain-to-computer interface (BCI) techniques that translate brain function to generate computer commands, we investigated the feasibility of using the FUS-based CBI to non-invasively establish a functional link between the brains of different species (i.e. human and Sprague-Dawley rat), thus creating a brain-to-brain interface (BBI). The implementation was aimed to non-invasively translate the human volunteer’s intention to stimulate a rat’s brain motor area that is responsible for the tail movement. The volunteer initiated the intention by looking at a strobe light flicker on a computer display, and the degree of synchronization in the electroencephalographic steady-state-visual-evoked-potentials (SSVEP) with respect to the strobe frequency was analyzed using a computer. Increased signal amplitude in the SSVEP, indicating the volunteer’s intention, triggered the delivery of a burst-mode FUS (350 kHz ultrasound frequency, tone burst duration of 0.5 ms, pulse repetition frequency of 1 kHz, given for 300 msec duration) to excite the motor area of an anesthetized rat transcranially. The successful excitation subsequently elicited the tail movement, which was detected by a motion sensor. The interface was achieved at 94.0±3.0% accuracy, with a time delay of 1.59±1.07 sec from the thought-initiation to the creation of the tail movement. Our results demonstrate the feasibility of a computer-mediated BBI that links central neural functions between two biological entities, which may confer unexplored opportunities in the study of neuroscience with potential implications for therapeutic applications.     

Hierarchical neuronal modeling of cognitive functions: from synaptic transmission to the Tower of London

Recent progress in the molecular biology of synaptic transmission, in particular of neurotransmitter receptors, offers novel information relevant to ‘realistic’ modeling of neural processes at the single cell and network level. Sophisticated computer analyses of 2D crystals by high resolution electron microscopy yield images of single neurotransmitter receptor molecules with tentative identifications of ligand binding sites and of conformational transitions. The dynamics of conformational changes can be accounted for by a ‘multistate allosteric network’ model. Allosteric receptors also possess the structural and functional properties required to serve as coincidence detectors between pre- and post-synaptic signals and, therefore, can be used as building blocks for a chemical Hebb synapse. These properties were introduced into networks of formal neurons capable of producing and detecting temporal sequences. In more elaborate models of pre-frontal cortex functions, allosteric receptors control the selection of transient ‘pre-representations’ and their stabilization by external or internal reward signals. We apply this scheme to Shallice's Tower of London test, and we show how a hierarchical neuronal architecture can implement executive or planning functions associated with frontal areas.     

Marine biodiversity and ecosystem services: an elusive link

Efforts to test the hypothesised positive link between ecosystem services and functions and biodiversity are increasing in order to forecast the consequences of the present erosion of biodiversity on ecosystem functions and to provide an additional basis for the conservation of biodiversity. These efforts have been, however, modest in marine ecosystems. An examination of seagrass communities, which are simple assemblages with a limited membership of about 50 species worldwide and <12 species in any one community, provides, however, strong evidence for the existence of such positive link between species richness and ecosystem functions. Ecosystem functions are, however, dependent on the particular membership of the community, rather that its number, for the functions are species-specific properties. Yet evidence, is provided, that an increasing species richness should be, on average, linked to an increase in the functional repertoire present in the community, will lead to a more efficient use of resources and a greater capacity to ensure the sustainability of ecosystem functions under disturbance or ecosystem change. Closer examination indicates that the functional variability of mixed-species seagrass assemblages is correlated to the variability in species size, whereas species of similar size tend to show similar functional capacities and, therefore, a greater degree of functional redundancy. In addition, the demonstration of positive interactions in seagrass communities, which are also dependent on the presence of engineering species in the community that facilitate the growth of other species, provides increasing grounds to expect an enhanced functional performance of mixed communities over that expected from a simple additive contribution of the community members. Multispecific communities also hold, within the functional repertoire they contain, many unrealised functional potentials that may prove instrumental to ensure the sustainability of ecosystem functions in the presence of disturbance or a changing environment. The arguments offered, illustrated for the comparatively simple seagrass communities, provide strong reasons to expect a strong — if difficult to test experimentally — positive relationship between species diversity and the functions of marine ecosystems and, thereby, the services they yield to humanity.     

EXCAVATOR: a computer program for efficiently mining gene expression data

Massive amounts of gene expression data are generated using microarrays for functional studies of genes and gene expression data clustering is a useful tool for studying the functional relationship among genes in a biological process. We have developed a computer package EXCAVATOR for clustering gene expression profiles based on our new framework for representing gene expression data as a minimum spanning tree. EXCAVATOR uses a number of rigorous and efficient clustering algorithms. This program has a number of unique features, including capabilities for: (i) data- constrained clustering; (ii) identification of genes with similar expression profiles to pre-specified seed genes; (iii) cluster identification from a noisy background; (iv) computational comparison between different clustering results of the same data set. EXCAVATOR can be run from a Unix/Linux/DOS shell, from a Java interface or from a Web server. The clustering results can be visualized as colored figures and 2-dimensional plots. Moreover, EXCAVATOR provides a wide range of options for data formats, distance measures, objective functions, clustering algorithms, methods to choose number of clusters, etc. The effectiveness of EXCAVATOR has been demonstrated on several experimental data sets. Its performance compares favorably against the popular K-means clustering method in terms of clustering quality and computing time.     

Aqueous hydration of nucleic acid constituents: Monte Carlo computer simulation studies

Monte Carlo computer simulations were performed on dilute aqueous solutions of thymine, cytosine, uracil, adenine, guanine, the dimethyl phosphate anion in the gauche-gauche conformation and a ribose and deoxyribose derivative. The aqueous hydration of each molecule was analysed in terms of quasi-component distribution functions based on the Proximity Criterion, and partitioned into hydrophobic, hydrophilic and ionic contributions. Color stereo views of selected hydration complexes are also presented. A preliminary discussion of the transferability of functional group coordination numbers is given. The results enable to comment on two current problems related to the hydration of nucleic acids: a) the theory of Dickerson and coworkers on the role of water in the relative stability of the A and B form of DNA and b) the idea of water bridges and filaments emerging from the computer simulation results on the hydration of DNA fragments by Clementi.