A probabilistic approach to microRNA-target binding

Elucidation of microRNA activity is a crucial step in understanding gene regulation. One key problem in this effort is how to model the pairwise interactions of microRNAs with their targets. As this interaction is strongly mediated by their sequences, it is desired to set-up a probabilistic model to explain the binding preferences between a microRNA sequence and the sequence of a putative target. To this end, we introduce a new model of microRNA-target binding, which transforms an aligned duplex to a new sequence and defines the likelihood of this sequence using a Variable Length Markov Chain. It offers a complementary representation of microRNA–mRNA pairs for microRNA target prediction tools or other probabilistic frameworks of integrative gene regulation analysis. The performance of present model is evaluated by its ability to predict microRNA–target mRNA interaction given a mature microRNA sequence and a putative mRNA binding site. In regard to classification accuracy, it outperforms two recent methods based on thermodynamic stability and sequence complementarity. The experiments can also unveil the effects of base pairing types and non-seed region in duplex formation.     

A probabilistic approach to the assessment of some life history pattern parameters in a Middle Pleistocene human population

Parameters of a Middle Pleistocene human population such as the expected length of the female reproductive period (E(Y)), the expected interbirth interval (E(X)), the survival rate (tau) for females after the expected reproductive period, the rate (phi(2)) of women who, given that they reach first birth, do not survive to the end of the expected reproductive period, and the female infant plus juvenile mortality rate (phi(1)) have been assessed from a probabilistic standpoint provided that such a population were stationary. The hominid sample studied, the Sima de los Huesos (SH) cave site, Sierra de Atapuerca (Spain), is the most exhaustive human fossil sample currently available. Results suggest that the Atapuerca (SH) sample can derive from a stationary population. Further, in the case that the expected reproductive period ends between 37 and 40 yr of age, then 24 less, similarE(Y) less, similar27 yr, E(X)=3 yr, 0.224相似文献   

A probabilistic approach to protein backbone tracing in electron density maps

One particularly time-consuming step in protein crystallography is interpreting the electron density map; that is, fitting a complete molecular model of the protein into a 3D image of the protein produced by the crystallographic process. In poor-quality electron density maps, the interpretation may require a significant amount of a crystallographer's time. Our work investigates automating the time-consuming initial backbone trace in poor-quality density maps. We describe ACMI (Automatic Crystallographic Map Interpreter), which uses a probabilistic model known as a Markov field to represent the protein. Residues of the protein are modeled as nodes in a graph, while edges model pairwise structural interactions. Modeling the protein in this manner allows the model to be flexible, considering an almost infinite number of possible conformations, while rejecting any that are physically impossible. Using an efficient algorithm for approximate inference--belief propagation--allows the most probable trace of the protein's backbone through the density map to be determined. We test ACMI on a set of ten protein density maps (at 2.5 to 4.0 A resolution), and compare our results to alternative approaches. At these resolutions, ACMI offers a more accurate backbone trace than current approaches.     

A note on the probabilistic approach to the cancer problem

Assuming that the initiation of cancer growth is due to a purely accidental fluctuation of some physicochemical condition, it is possible to derive the equation for the cancer incidence as a function of age. The final result depends on whether it is assumed that a single accidental fluctuation in a cell is sufficient to produce cancer, or that a finite number,k, of repetitions of the accidental fluctuation must occur in the same cell. In principle it is possible to determine from observed incidence curves the numberk. Actually, however, this cannot be done at present, because the difference of the theoretical curves for differentk's is rather small, and the available cancer statistics are not accurate enough to show such differences.     

A quantum-theoretic approach to genetic problems

A quantum-theoretic picture of the transfer of genetic information is described. The advantage of such an approach is that a number of genetic effects appear to be explicable on the basis of general microphysical laws, independent of any specific model (such as DNA-protein coding) for the transmission of genetic information. It is assumed that the genetic information is carried by a family of numerical observables belonging to a specific microphysical system; it is shown that a single observable is theoretically sufficient to carry this information. The various types of structure that this observable can possess are then described in detail, and the possible genetic effects which can airse from each such structure are discussed. For example, it is shown how the assumption that the genetic observable possesses degenerate eigenvalues may lead to a theory of allelism. To keep the treatment self-contained, the basic quantum-theoretical principles to be used are discussed in some detail. Finally, the relation of the present approach to current biochemical ideas and to earlier quantum-theoretic treatments of genetic systems is discussed.     

A probabilistic approach to compact steady-state kinetic equations for enzymic reactions

We describe a method for deriving kinetic equations based on the simplification of a complex graphical scheme of steady-state enzymic reactions to one that is comprised of an unbranched pathway. It entails compressing unbranched multi-step sequences into one step, and fusing some graph nodes into a single node. The final form of the equations is compact and well structured, and it simplifies the choice of independent kinetic parameters. The approach is illustrated by an analysis of representative two- and three-substrate reactions.     

A probabilistic approach to estimating species pools from large compositional matrices

Abstract. Species pools are increasingly recognized as important controls of local plant community structure and diversity. While existing approaches to estimate their content and size either rely on phytosociological expert knowledge or on simple response models across environmental gradients, the proposed application of phytosociological smoothing according to Beals exploits the full information of plant co‐occurrence patterns statistically. Where numerous representative compositional data are available, the new method yields robust estimates of the potential of sites to harbour plant species. To test the new method, a large phytosociological databank covering the forested regions of Oregon (US) was subsampled randomly and evenly across strata defined by geographic regions and elevation belts. The resulting matrix of species presence/absence in 874 plots was smoothed by calculating Beals' index of sociological favourability, which estimates the probability of encountering each species at each site from the actual plot composition and the pattern of species co‐occurrence in the matrix. In a second step, the resulting lists of sociologically probable species were intersected with complete species lists for each of 14 geographical subregions. Species pools were compared to observed species composition and richness. Species pool size exhibited much clearer spatial trends than plot richness and could be modelled much better as a function of climatic factors. In this framework the goal of modelling species pools is not to test a hypothesis, but to bridge the gap between manageable scales of empirical observation and the spatio‐temporal hierarchy of diversity patterns.     

A frequency matrix for probabilistic identification of some bacilli

A matrix comprising frequencies for positive results for 44 Bacillus taxa for 30 characters has been constructed. The 44 taxa include most of the common species and several clusters of environmental isolates including those described as B. firmus-B. lentus intermediates. The tests, which were chosen for their high diagnostic value, included some of the traditional tests used for identification of bacilli supplemented with a range of sugar fermentations and other characterization tests. The matrix was evaluated by identifying hypothetical median organisms, cluster representatives and a panel of 23 reference strains. All reference strains achieved Willcox probabilities above 0.995. Fifty-eight environmental isolates were also subjected to the 30 tests and identification was attempted. Forty-one strains (70%) achieved a Willcox probability greater than 0.95, which was considered an acceptable identification, and were assigned to 12 taxa. If the SE of taxonomic distance was also considered in the identification score (an acceptable value being less than 7.0), the number of acceptable identifications was reduced to 34 (59%). It was encouraging that bacteria from garden soils identified to the common species such as B. subtilis, B. cereus and B. licheniformis whereas some of the bacteria from an estuarine habitat were identified as species such as B. firmus which are normally identified with that habitat.     

A probabilistic approach for estimating water permeability in pressure-driven membranes

A probabilistic approach is proposed to estimate water permeability in a cellulose triacetate (CTA) membrane. Water transport across the membrane is simulated in reverse osmosis mode by means of non-equilibrium molecular dynamics (MD) simulations. Different membrane configurations obtained by an annealing MD simulation are considered and simulation results are analyzed by using a hierarchical Bayesian model to obtain the permeability of the different membranes. The estimated membrane permeability is used to predict full-scale water flux by means of a process-level Monte Carlo simulation. Based on the results, the parameters of the model are observed to converge within 5-ns total simulation time. The results also indicate that the use of unique structural configurations in MD simulations is essential to capture realistic membrane properties at the molecular scale. Furthermore, the predicted full-scale water flux based on the estimated permeability is within the same order of magnitude of bench-scale experimental measurement of 1.72×10^?5 m/s.     

A biomimetic approach to some specifically functionalized cyclic terpenoids

The paper relates on the current advancements in the synthesis of complex cyclic terpenoids by superacidic induced cyclization of open chain precursors. It is shown that functional groups disposal in the initial substrate strongly influences the reaction outcome. Possible variations of the investigated compound structures include particularly alpha-functionalization and alpha,omega-bifunctionalization. This approach allowed a selective initiation of cyclization sequence from an internal double bond or suspending the ring closure cascade to partially cyclized compounds. The reported synthetic schemes are attempts to mimic the biogenetical processes postulated in the living systems.     

A probabilistic approach for validating protein NMR chemical shift assignments

It has been estimated that more than 20% of the proteins in the BMRB are improperly referenced and that about 1% of all chemical shift assignments are mis-assigned. These statistics also reflect the likelihood that any newly assigned protein will have shift assignment or shift referencing errors. The relatively high frequency of these errors continues to be a concern for the biomolecular NMR community. While several programs do exist to detect and/or correct chemical shift mis-referencing or chemical shift mis-assignments, most can only do one, or the other. The one program (SHIFTCOR) that is capable of handling both chemical shift mis-referencing and mis-assignments, requires the 3D structure coordinates of the target protein. Given that chemical shift mis-assignments and chemical shift re-referencing issues should ideally be addressed prior to 3D structure determination, there is a clear need to develop a structure-independent approach. Here, we present a new structure-independent protocol, which is based on using residue-specific and secondary structure-specific chemical shift distributions calculated over small (3–6 residue) fragments to identify mis-assigned resonances. The method is also able to identify and re-reference mis-referenced chemical shift assignments. Comparisons against existing re-referencing or mis-assignment detection programs show that the method is as good or superior to existing approaches. The protocol described here has been implemented into a freely available Java program called “Probabilistic Approach for protein Nmr Assignment Validation (PANAV)” and as a web server () which can be used to validate and/or correct as well as re-reference assigned protein chemical shifts.     

Outline of a probabilistic approach to animal sociology: III

The probabilities of the emergence of the two kinds of social structure in a 3-bird flock (chain and cycle) are deduced under the assumption of certain biases acting on the social dynamics of the flock. In particular a bias against the reversal of peck order and a bias against encounters of individuals of disparate social rank are considered. Like-wise a distribution of an “inherent” fighting ability is considered which influences the outcomes of encounters. A functional relation is derived between the importance of this ability and the initial probability of a chain structure.     

Outline of a probabilistic approach to animal sociology: I

The non-transitive character of he peck right relation gives rise to different “social structures” in an aggregate of individuals. A method is developed for computing the respective probabilities of occurrence for each type of structure in small aggregates on the basis of random determination of peck right between each pair of individuals.     

Outline of a probabilistic approach to animal sociology: II

Under certain assumptions concerning the probabilities of “mutations,” i.e. changes of structure of bird societies, it is shown that the probability distribution for all possible structures of a society ofN individuals approaches a limit independent of the initial probability distribution. A formula for the limiting distribution is derived.     

Computation of biopolymers: A general approach to different problems

A comparative analysis of some effective algorithms widely used in analysis, computation and comparison of chain molecules is presented. A notion of a stream in an oriented hypergraph is introduced, which generalizes a notion of a path in a graph. All considered algorithms looking over exponential sets of structures in polynomial time can be described as variants of a general algorithm of analysis of paths in graphs and of streams in oriented hypergraphs.     

Evaluating risks of biological control introductions: A probabilistic risk-assessment approach

We address the need to develop improved quantitative procedures for estimating potential non-target impacts of biological control agents in this paper, and propose a probabilistic risk-assessment approach. This approach employs risk-assessment procedures commonly used in many disciplines. The procedure described here uses precision trees to estimate risk based on probabilities that biological control agents will demonstrate predictable behavior under specific conditions, based on their ecological characteristics. We use Trichogramma ostriniae, an egg parasitoid deployed augmentatively against Ostrina nubilalis in the US as case study to conceptually demonstrate the proposed procedure. We propose that this new approach has potential for widespread use in quantifying non-target risk of biological control introductions prior to introductions being made.