Equational Axiomization of Bicoercibility for Polymorphic Types

Two polymorphic types σ and τ are said to be bicoercible if there is a coercion from σ to τ and conversely. We give a complete equational axiomatization of bicoercible types and prove that the relation of bicoercibility is decidable.National Science Foundation (CCR-9113196); KBN (2 P301 031 06); ESPRIT BRA7232 GENTZE

Unique fixed points vs. least fixed points

AbstractThe aim of this paper is to compare two approaches to the semantics of programming languages: the least fixed point approach, and the unique fixed point approach. Briefly speaking, we investigate here the problem of existence of extensions of algebras with the unique fixed point property to ordered algebras with the least fixed point property, that preserve the fixed point solutions. We prove that such extensions always exist, the construction of a free extension is given. It is also shown that in some cases there is no ‘faithful’ extension, i.e. some elements of a carrier are always collapsed

MEMOFinder: combining _de_ _novo_ motif prediction methods with a database of known motifs

*Background:* Methods for finding overrepresented sequence motifs are useful in several key areas of computational biology. They aim at detecting very weak signals responsible for biological processes requiring robust sequence identification like transcription-factor binding to DNA or docking sites in proteins. Currently, general performance of the model-based motif-finding methods is unsatisfactory; however, different methods are successful in different cases. This leads to the practical problem of combining results of different motif-finding tools, taking into account current knowledge collected in motif databases.
*Results:* We propose a new complete service allowing researchers to submit their sequences for analysis by four different motif-finding methods for clustering and comparison with a reference motif database. It is tailored for regulatory motif detection, however it allows for substantial amount of configuration regarding sequence background, motif database and parameters for motif-finding methods.
*Availability:* The method is available online as a webserver at: http://bioputer.mimuw.edu.pl/software/mmf/. In addition, the source code is released on a GNU General Public License

CAMBer: an approach to support comparative analysis of multiple bacterial strains

10.1109/BIBM.2010.5706549Proceedings - 2010 IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2010121-12

Another incompleteness result for Hoare's logic

It is known (Bergstra and Tucker (1982) J. Comput. System Sci. 25, 217) that if the Hoare rules are complete for a first-order structure %plane1D;49C;, then the set of partial correctness assertions true over %plane1D;49C; is recursive in the first-order theory of %plane1D;49C;. We show that the converse is not true. Namely, there is a first-order structure %plane1D;49E; such that the set of partial correctness assertions true over %plane1D;49E; is recursive in the theory of %plane1D;49E;, but the Hoare rules are not complete for %plane1D;49E;

Finding evolutionarily conserved cis-regulatory modules with a universal set of motifs

<p>Abstract</p> <p>Background</p> <p>Finding functional regulatory elements in DNA sequences is a very important problem in computational biology and providing a reliable algorithm for this task would be a major step towards understanding regulatory mechanisms on genome-wide scale. Major obstacles in this respect are that the fact that the amount of non-coding DNA is vast, and that the methods for predicting functional transcription factor binding sites tend to produce results with a high percentage of false positives. This makes the problem of finding regions significantly enriched in binding sites difficult.</p> <p>Results</p> <p>We develop a novel method for predicting regulatory regions in DNA sequences, which is designed to exploit the evolutionary conservation of regulatory elements between species without assuming that the order of motifs is preserved across species. We have implemented our method and tested its predictive abilities on various datasets from different organisms.</p> <p>Conclusion</p> <p>We show that our approach enables us to find a majority of the known CRMs using only sequence information from different species together with currently publicly available motif data. Also, our method is robust enough to perform well in predicting CRMs, despite differences in tissue specificity and even across species, provided that the evolutionary distances between compared species do not change substantially. The complexity of the proposed algorithm is polynomial, and the observed running times show that it may be readily applied.</p

The R Package bgmm : Mixture Modeling with Uncertain Knowledge

Classical supervised learning enjoys the luxury of accessing the true known labels for the observations in a modeled dataset. Real life, however, poses an abundance of problems, where the labels are only partially defined, i.e., are uncertain and given only for a subsetof observations. Such partial labels can occur regardless of the knowledge source. For example, an experimental assessment of labels may have limited capacity and is prone to measurement errors. Also expert knowledge is often restricted to a specialized area and is thus unlikely to provide trustworthy labels for all observations in the dataset. Partially supervised mixture modeling is able to process such sparse and imprecise input. Here, we present an R package calledbgmm, which implements two partially supervised mixture modeling methods: soft-label and belief-based modeling. For completeness, we equipped the package also with the functionality of unsupervised, semi- and fully supervised mixture modeling. On real data we present the usage of bgmm for basic model-fitting in all modeling variants. The package can be applied also to selection of the best-fitting from a set of models with different component numbers or constraints on their structures. This functionality is presented on an artificial dataset, which can be simulated in bgmm from a distribution defined by a given model

Comprehensive prediction in 78 human cell lines reveals rigidity and compactness of transcription factor dimers

The binding of transcription factors (TFs) to their specific motifs in genomic regulatory regions is commonly studied in isolation. However, in order to elucidate the mechanisms of transcriptional regulation, it is essential to determine which TFs bind DNA cooperatively as dimers and to infer the precise nature of these interactions. So far, only a small number of such dimeric complexes are known. Here, we present an algorithm for predicting cell-type-specific TF-TF dimerization on DNA on a large scale, using DNase I hypersensitivity data from 78 human cell lines. We represented the universe of possible TF complexes by their corresponding motif complexes, and analyzed their occurrence at cell-type-specific DNase I hypersensitive sites. Based on ~1.4 billion tests for motif complex enrichment, we predicted 603 highly significant celltype- specific TF dimers, the vast majority of which are novel. Our predictions included 76% (19/25) of the known dimeric complexes and showed significant overlap with an e xperimental database of protein-protein interactions. They were also independently supported by evolutionary conservation, as well as quantitative variation in DNase I digestion patterns. Notably, the known and predicted TF dimers were almost always highly compact and rigidly spaced, suggesting that TFs dimerize in close proximity to their partners, which results in strict constraints on the structure of the DNA-bound complex. Overall, our results indicate that chromatin openness profiles are highly predictive of cell-type-specific TF-TF interactions. Moreover, cooperative TF dimerization seems to be a widespread phenomenon, with multiple TF complexes predicted in most cell types. © 2013, Published by Cold Spring Harbor Laboratory Press.Link_to_subscribed_fulltex

Applying dynamic Bayesian networks to perturbed gene expression data

BACKGROUND: A central goal of molecular biology is to understand the regulatory mechanisms of gene transcription and protein synthesis. Because of their solid basis in statistics, allowing to deal with the stochastic aspects of gene expressions and noisy measurements in a natural way, Bayesian networks appear attractive in the field of inferring gene interactions structure from microarray experiments data. However, the basic formalism has some disadvantages, e.g. it is sometimes hard to distinguish between the origin and the target of an interaction. Two kinds of microarray experiments yield data particularly rich in information regarding the direction of interactions: time series and perturbation experiments. In order to correctly handle them, the basic formalism must be modified. For example, dynamic Bayesian networks (DBN) apply to time series microarray data. To our knowledge the DBN technique has not been applied in the context of perturbation experiments. RESULTS: We extend the framework of dynamic Bayesian networks in order to incorporate perturbations. Moreover, an exact algorithm for inferring an optimal network is proposed and a discretization method specialized for time series data from perturbation experiments is introduced. We apply our procedure to realistic simulations data. The results are compared with those obtained by standard DBN learning techniques. Moreover, the advantages of using exact learning algorithm instead of heuristic methods are analyzed. CONCLUSION: We show that the quality of inferred networks dramatically improves when using data from perturbation experiments. We also conclude that the exact algorithm should be used when it is possible, i.e. when considered set of genes is small enough