An alphabetic code based atomic level molecular similarity search in databases

Atomic level molecular similarity and diversity studies have gained considerable importance through their wide application in Bioinformatics and Chemo-informatics for drug design. The availability of large volumes of data on chemical compounds requires new methodologies for efficient and effective searching of its archives in less time with optimal computational power. We describe an alphabetic algorithm for similarity searching based on atom-atom bonding preference for ligands. We represented 170 cyclindependent kinase 2 inhibitors using strings of pre-defined alphabets for searching using known protein sequence alignment tools. Thus, a common pattern was extracted using this set of compounds for database searching to retrieve similar active compounds. Area under the receiver operating characteristic (ROC) curve was used for the discrimination of similar and dissimilar compounds in the databases. An average retrieval rate of about 60% is obtained in cross-validation using the home-grown dataset and the directory of useful decoys (DUD, formally known as the ZINC database) data. This will help in the effective retrieval of similar compounds using database search.     

Searching for three-dimensional secondary structural patterns in proteins with ProSMoS

MOTIVATION: Many evolutionarily distant, but functionally meaningful links between proteins come to light through comparison of spatial structures. Most programs that assess structural similarity compare two proteins to each other and find regions in common between them. Structural classification experts look for a particular structural motif instead. Programs base similarity scores on superposition or closeness of either Cartesian coordinates or inter-residue contacts. Experts pay more attention to the general orientation of the main chain and mutual spatial arrangement of secondary structural elements. There is a need for a computational tool to find proteins with the same secondary structures, topological connections and spatial architecture, regardless of subtle differences in 3D coordinates. RESULTS: We developed ProSMoS--a Protein Structure Motif Search program that emulates an expert. Starting from a spatial structure, the program uses previously delineated secondary structural elements. A meta-matrix of interactions between the elements (parallel or antiparallel) minding handedness of connections (left or right) and other features (e.g. element lengths and hydrogen bonds) is constructed prior to or during the searches. All structures are reduced to such meta-matrices that contain just enough information to define a protein fold, but this definition remains very general and deviations in 3D coordinates are tolerated. User supplies a meta-matrix for a structural motif of interest, and ProSMoS finds all proteins in the protein data bank (PDB) that match the meta-matrix. ProSMoS performance is compared to other programs and is illustrated on a beta-Grasp motif. A brief analysis of all beta-Grasp-containing proteins is presented. Program availability: ProSMoS is freely available for non-commercial use from ftp://iole.swmed.edu/pub/ProSMoS.     

Automated generation of MCSS-derived pharmacophoric DOCK site points for searching multiconformation databases

All docking methods employ some sort of heuristic to orient the ligand molecules into the binding site of the target structure. An automated method, MCSS2SPTS, for generating chemically labeled site points for docking is presented. MCSS2SPTS employs the program Multiple Copy Simultaneous Search (MCSS) to determine target-based theoretical pharmacophores. More specifically, chemically labeled site points are automatically extracted from selected low-energy functional-group minima and clustered together. These pharmacophoric site points can then be directly matched to the pharmacophoric features of database molecules with the use of either DOCK or PhDOCK to place the small molecules into the binding site. Several examples of the ability of MCSS2SPTS to reproduce the three-dimensional pharmacophoric features of ligands from known ligand-protein complex structures are discussed. In addition, a site-point set calculated for one human immunodeficiency virus 1 (HIV1) protease structure is used with PhDOCK to dock a set of HIV1 protease ligands; the docked poses are compared to the corresponding complex structures of the ligands. Finally, the use of an MCSS2SPTS-derived site-point set for acyl carrier protein synthase is compared to the use of atomic positions from a bound ligand as site points for a large-scale DOCK search. In general, MCSS2SPTS-generated site points focus the search on the more relevant areas and thereby allow for more effective sampling of the target site.     

Automated motif extraction and classification in RNA tertiary structures

We used a novel graph-based approach to extract RNA tertiary motifs. We cataloged them all and clustered them using an innovative graph similarity measure. We applied our method to three widely studied structures: Haloarcula marismortui 50S (H.m 50S), Escherichia coli 50S (E. coli 50S), and Thermus thermophilus 16S (T.th 16S) RNAs. We identified 10 known motifs without any prior knowledge of their shapes or positions. We additionally identified four putative new motifs.     

A normalized root-mean-square distance for comparing protein three-dimensional structures.

The degree of similarity of two protein three-dimensional structures is usually measured with the root-mean-square distance between equivalent atom pairs. Such a similarity measure depends on the dimension of the proteins, that is, on the number of equivalent atom pairs. The present communication presents a simple procedure to make the root-mean-square distances between pairs of three-dimensional structures independent of their dimensions. This normalization may be useful in evolutionary and fold classification studies as well as in simple comparisons between different structural models.     

Analysis and Design of an Agent Searching Algorithm for e-Marketplaces

Recently, agent techniques in electronic marketplaces (e-marketplaces) bring B-to-B trading into a new era. However, not much analysis on the behavior of agents has been reported. In this paper, based on the ant algorithm in network routing, we introduce a jumping (searching) model for agents in an e-marketplace network. However, we should be aware that if there are too many agents in the e-marketplace network, they will use up all communication bandwidth and computing resource. It is inevitable to investigate the behavior of agents, such as agent population. Based on the existing results in the ant algorithm in network routing, we present the behavior of agents in an e-marketplace network. Hence, we can control the agent population by setting the appropriate agent generation rate.     

我国植物检疫性菌物数据库平台的建设及应用

近年来，随着我国对外贸易的不断增长，口岸检测样品量巨大，外来检疫性有害生物尤其是病原菌物传入我国的风险日趋增加，正成为我国国门生物安全的重要威胁。加强外来入侵菌物的防御能力建设，有效防范其造成的生物安全威胁迫在眉睫。由于外来入侵菌物各类群的基础研究薄弱，标准参比物质缺乏、基础数据和可检索数据库缺失，大部分物种缺乏准确、高效的鉴定手段，使得现有口岸菌物检疫存在准确性较低、速度较慢、误检漏检率较高等问题。针对上述问题，以我国进境检疫对象及主要进口农林作物上的高频检出但鉴定困难、误检率高的菌物类群为对象，建立了其标准参比物质库、形态特征信息库、多基因序列数据库，并通过整合多个信息库资源实现从检疫样品中初筛到物种精准鉴定的多模块服务平台www.casbrc.org/pqfungi，并开放共享。该数据库平台的应用有望促进我国口岸检疫部门的检测便利化水平大幅提升，在“智能海关”建设、维护国门生物安全及促进农林产品安全贸易中发挥重要作用。     

Chemical morphogenesis: Turing patterns in an experimental chemical system

Patterns resulting from the sole interplay between reaction and diffusion are probably involved in certain stages of morphogenesis in biological systems, as initially proposed by Alan Turing. Self-organization phenomena of this type can only develop in nonlinear systems (i.e. involving positive and negative feedback loops) maintained far from equilibrium. We present Turing patterns experimentally observed in a chemical system. An oscillating chemical reaction, the CIMA reaction, is operated in an open spatial reactor designed in order to obtain a pure reaction-diffusion system. The two types of Turing patterns observed, hexagonal arrays of spots and parallel stripes, are characterized by an intrinsic wavelength. We identify the origin of the necessary difference of diffusivity between activator and inhibitor. We also describe a pattern growth mechanism by spot splitting that recalls cell division.     

Contrasting patterns of elevational zonation for birds and mammals in the Andes of southeastern Peru

Abstract. To determine the generality of avian diversity patterns, we investigated patterns of elevational zonation shown by birds and mammals along the eastern slope of the Andes Mountains in southeastern Peru. The strong environmental gradient sampled, entirely within Peru's Manu National Park and Biosphere Reserve, supports highly diverse faunas. Elevational distributions of 901 bird species, 129 bat species, and twenty-eight species of native mice exhibit contrasting patterns in species richness, species composition, and species turnover. Birds and bats showed smooth declines of species richness with elevation, whereas the richness of mouse assemblages was unrelated to elevation. For all three groups, the greatest differences were between lowland and highland faunas, although cutoff points for this contrast varied among groups (≈ 500 m for birds, 750 m for bats, and 1000 m for mice). Differences in composition also separated bird and bat faunas on either side of c. 1400 m (the boundary between montance forest and cloud forest); for mice, this faunal transition may take place nearer to 2000 m. Bird and bat faunas lacked the more discrete zonations suggested for mouse assemblages, as indicated by elevational range profiles and nested subset analyses. Distinct highland assemblages are apparent in two-dimensional histograms of range limits of birds and mice, but not for bats. Highland bat species occupy broader elevational ranges than lowland bat species, but for both birds and mice, species at intermediate elevations had the broadest amplitudes. Finally, clumping of range maxima and minima along the gradient identified zones of pronounced species turnover in each group, but these were generally not strongly associated with the locations of ecotones. Differences in zonation of these groups appear to reflect their different biological attributes and phylogenetic histories. Such differences obviously complicate discussions of ‘general’ diversity patterns, and limit the usefulness of birds to forecast or predict diversity patterns in other more poorly known groups—other groups may show elevated diversity and endemism in areas where avian diversity patterns appear unremarkable. The pronounced contrasts between bats and mice, and the generally intermediate character of avian patterns, suggest that future analyses might profitably partition birds into finer, more homogeneous groups of historically and/or ecologically similar species. Group differences in zonation may ultimately prove explicable with information on both species-abundance patterns and resource distributions.     

The diet transform of lattice patterns,equivalence relations,and similarity measures

The diet algorithm is introduced for the reduction of square-cell lattice patterns to simpler graphs that contain fewer C ₄ cells. By repeated applications of the algorithm, the lattice pattern is converted into a graph representing the skeletal structure of the pattern. Based on the algorithm, equivalence relations and dissimilarity measures are introduced for lattice patterns, providing tools for shape analysis of planar patterns, such as projections of molecular contour surfaces used in molecular design. This algorithm is applied to a series of examples, illustrating the features of the method.     

Comparison of methods for searching protein sequence databases.

We have compared commonly used sequence comparison algorithms, scoring matrices, and gap penalties using a method that identifies statistically significant differences in performance. Search sensitivity with either the Smith-Waterman algorithm or FASTA is significantly improved by using modern scoring matrices, such as BLOSUM45-55, and optimized gap penalties instead of the conventional PAM250 matrix. More dramatic improvement can be obtained by scaling similarity scores by the logarithm of the length of the library sequence (In()-scaling). With the best modern scoring matrix (BLOSUM55 or JO93) and optimal gap penalties (-12 for the first residue in the gap and -2 for additional residues), Smith-Waterman and FASTA performed significantly better than BLASTP. With In()-scaling and optimal scoring matrices (BLOSUM45 or Gonnet92) and gap penalties (-12, -1), the rigorous Smith-Waterman algorithm performs better than either BLASTP and FASTA, although with the Gonnet92 matrix the difference with FASTA was not significant. Ln()-scaling performed better than normalization based on other simple functions of library sequence length. Ln()-scaling also performed better than scores based on normalized variance, but the differences were not statistically significant for the BLOSUM50 and Gonnet92 matrices. Optimal scoring matrices and gap penalties are reported for Smith-Waterman and FASTA, using conventional or In()-scaled similarity scores. Searches with no penalty for gap extension, or no penalty for gap opening, or an infinite penalty for gaps performed significantly worse than the best methods. Differences in performance between FASTA and Smith-Waterman were not significant when partial query sequences were used. However, the best performance with complete query sequences was obtained with the Smith-Waterman algorithm and In()-scaling.     

Competition can lead to unexpected patterns in tropical ant communities

Ecological communities are structured by competitive, predatory, mutualistic and parasitic interactions combined with chance events. Separating deterministic from stochastic processes is possible, but finding statistical evidence for specific biological interactions is challenging. We attempt to solve this problem for ant communities nesting in epiphytic bird’s nest ferns (Asplenium nidus) in Borneo’s lowland rainforest. By recording the frequencies with which each and every single ant species occurred together, we were able to test statistically for patterns associated with interspecific competition. We found evidence for competition, but the resulting co-occurrence pattern was the opposite of what we expected. Rather than detecting species segregation—the classical hallmark of competition—we found species aggregation. Moreover, our approach of testing individual pairwise interactions mostly revealed spatially positive rather than negative associations. Significant negative interactions were only detected among large ants, and among species of the subfamily Ponerinae. Remarkably, the results from this study, and from a corroborating analysis of ant communities known to be structured by competition, suggest that competition within the ants leads to species aggregation rather than segregation. We believe this unexpected result is linked with the displacement of species following asymmetric competition. We conclude that analysing co-occurrence frequencies across complete species assemblages, separately for each species, and for each unique pairwise combination of species, represents a subtle yet powerful way of detecting structure and compartmentalisation in ecological communities.     

Relevance of chronotype for eating patterns in adolescents

During adolescence, a shift from morningness to eveningness occurs, yet school continues to start early in the morning. Hence, adolescents are at risk for social jetlag, i.e. a discrepancy between biological and social timing. It remains to be determined whether chronotype associates with daily and daytime-specific eating patterns during this potentially critical period. Therefore, the aim of the present study was to investigate whether chronotype is decisive for daily eating patterns [total energy intake (TEI, kcal), total macronutrient intake (% of TEI), eating occasion frequency (n/day), meal frequency (n/day), snack frequency (n/day), duration of nightly fasting], or daytime-specific eating patterns [morning (before 11 am) energy intake (% of TEI), morning macronutrient intake (% of morning energy intake), regular breakfast skipping (no morning energy intake at least on 2 of 3?days, yes/no), evening (after 6 pm) energy intake (% of TEI), evening macronutrient intake (% of evening energy intake), regular dinner skipping (no evening energy intake at least on 2 of 3?days, yes/no)] in German adolescents. Chronotype was assessed by use of the Munich Chronotype Questionnaire and is defined as the midpoint of sleep corrected for sleep-debt accumulated over the workweek (the later the midpoint of sleep, the later the chronotype). A total of 223 participants (10–18?years) provided 346 questionnaires and concurrent 3-day weighed dietary records. Associations between chronotype and eating patterns were analyzed cross-sectionally using multivariable linear and logistic mixed-effects regression models. Adolescents with earlier and later chronotypes did not differ in their daily eating patterns. With respect to daytime-specific eating patterns, 1?h delay in chronotype was associated with 4.0 (95% CI 2.5–6.6) greater odds of regular breakfast skipping (p < 0.0001). In addition, later chronotype was associated with higher evening energy intake (p = 0.0009). In conclusion, our data show that a later chronotype among adolescents is associated with a shift of food consumption toward later times of the day. Hence, adolescents’ eating patterns appear to follow their internal clock rather than socially determined schedules.     

The use of specimen-label databases for conservation purposes: an example using Mexican Papilionid and Pierid butterflies

In recent years, use of databases of the labels of specimens deposited in museums and herbaria is becoming increasingly common as a tool for addressing biodiversity conservation and management problems. These databases are often large in size and complex in structure, and their application to conservation deserves a wider appreciation of some of the biases, gaps and potential pitfalls common to them. In this paper, we discuss some of the problems associated with using such databases for obtaining lists of species for arbitrary sites, as well as for the estimation of the distribution area of single species. The possibility of obtaining these closely related variables using specimen databases is shown to be scale-dependent. A tool based on mark-recapture techniques is applied to the problem of: (i) detecting sites with low number of species due to lack of adequate in-site sampling and, (ii) species with small estimated areas due to poor spatial coverage of samples.     

The application of databases and PCR in the cloning of glycosidase genes from the protozoan Tritrichomonas foetus

Conserved sequence amplification (CSA) has been used to obtain sequence data for two glycosidase genes from the primitive eukaryote Tritrichomonas foetus. Few genes have been cloned from this organism, and there is little information concerning protein sequence. CSA is reliant on the use of database searches to identify short sequences of 3–9 amino acids conserved within a protein across a wide range of species. PCR primers are then constructed based on this sequence data and the DNA is amplified and sequenced. In the case of the β-galactosidase gene, N-terminal amino acid sequence data were used to construct a primer that replaced the upstream primer to ensure the amplified product was related to β-d galactosidase CSA was also applied to the gene encoding the enzyme β-N-acetyl-d-glucosaminidase from T. foetus, but in this case a segment of DNA was amplified, which, if correct, should contain a third conserved motif. The products of the CSA were sequenced, and the data obtained were compared to data in the SwissProt database. The results obtained suggest that this approach is useful for the cloning of genes to obtain novel sequence data from organisms where little genetic information is available.     

Fantastic databases and where to find them: Web applications for researchers in a rush

Public databases are essential to the development of multi-omics resources. The amount of data created by biological technologies needs a systematic and organized form of storage, that can quickly be accessed, and managed. This is the objective of a biological database. Here, we present an overview of human databases with web applications. The databases and tools allow the search of biological sequences, genes and genomes, gene expression patterns, epigenetic variation, protein-protein interactions, variant frequency, regulatory elements, and comparative analysis between human and model organisms. Our goal is to provide an opportunity for exploring large datasets and analyzing the data for users with little or no programming skills. Public user-friendly web-based databases facilitate data mining and the search for information applicable to healthcare professionals. Besides, biological databases are essential to improve biomedical search sensitivity and efficiency and merge multiple datasets needed to share data and build global initiatives for the diagnosis, prognosis, and discovery of new treatments for genetic diseases. To show the databases at work, we present a a case study using ACE2 as example of a gene to be investigated. The analysis and the complete list of databases is available in the following website <https://kur1sutaru.github.io/fantastic_databases_and_where_to_find_them/>.     

Persistent spatial patterns for semi-discrete models of excitable media

Excitable media have the property that in the spatially homogeneous configuration there is a globally asymptotically stable equilibrium, and no sustained non-decaying oscillations are possible. If diffusion effects are present, however, experiments seem to indicate the possibility of persistent oscillations. In more than one space dimension this may occur, apparently, even if the initial disturbance is restricted to a compact subset of an open domain in the medium. In this paper we discuss a mathematical model of this phenomenon. The model consists of a doubly infinite coupled system of ordinary differential equations, and therefore is intended to represent a spatially discrete network of interconnected cells.