The Process-Interaction-Model: a common representation of rule-based and logical models allows studying signal transduction on different levels of detail

BACKGROUND: Signaling systems typically involve large, structured molecules each consisting of a large number of subunits called molecule domains. In modeling such systems these domains can be considered as the main players. In order to handle the resulting combinatorial complexity, rule-based modeling has been established as the tool of choice. In contrast to the detailed quantitative rule-based modeling, qualitative modeling approaches like logical modeling rely solely on the network structure and are particularly useful for analyzing structural and functional properties of signaling systems. RESULTS: We introduce the Process-Interaction-Model (PIM) concept. It defines a common representation (or basis) of rule-based models and site-specific logical models, and, furthermore, includes methods to derive models of both types from a given PIM. A PIM is based on directed graphs with nodes representing processes like post-translational modifications or binding processes and edges representing the interactions among processes. The applicability of the concept has been demonstrated by applying it to a model describing EGF insulin crosstalk. A prototypic implementation of the PIM concept has been integrated in the modeling software ProMoT. CONCLUSIONS: The PIM concept provides a common basis for two modeling formalisms tailored to the study of signaling systems: a quantitative (rule-based) and a qualitative (logical) modeling formalism. Every PIM is a compact specification of a rule-based model and facilitates the systematic set-up of a rule-based model, while at the same time facilitating the automatic generation of a site-specific logical model. Consequently, modifications can be made on the underlying basis and then be propagated into the different model specifications – ensuring consistency of all models, regardless of the modeling formalism. This facilitates the analysis of a system on different levels of detail as it guarantees the application of established simulation and analysis methods to consistent descriptions (rule-based and logical) of a particular signaling system

Boolean Models of Bistable Biological Systems

This paper presents an algorithm for approximating certain types of dynamical systems given by a system of ordinary delay differential equations by a Boolean network model. Often Boolean models are much simpler to understand than complex differential equations models. The motivation for this work comes from mathematical systems biology. While Boolean mechanisms do not provide information about exact concentration rates or time scales, they are often sufficient to capture steady states and other key dynamics. Due to their intuitive nature, such models are very appealing to researchers in the life sciences. This paper is focused on dynamical systems that exhibit bistability and are desc ribedby delay equations. It is shown that if a certain motif including a feedback loop is present in the wiring diagram of the system, the Boolean model captures the bistability of molecular switches. The method is appl ied to two examples from biology, the lac operon and the phage lambda lysis/lysogeny switch

Subgenome Dominance in an Interspecific Hybrid, Synthetic Allopolyploid, and a 140-Year-Old Naturally Established Neo-Allopolyploid Monkeyflower

Recent studies have shown that one of the parental subgenomes in ancient polyploids is generally more dominant, having retained more genes and being more highly expressed, a phenomenon termed subgenome dominance. The genomic features that determine how quickly and which subgenome dominates within a newly formed polyploid remain poorly understood. To investigate the rate of emergence of subgenome dominance, we examined gene expression, gene methylation, and transposable element (TE) methylation in a natural, \u3c140-year-old allopolyploid (Mimulus peregrinus), a resynthesized interspecies triploid hybrid (M. robertsii), a resynthesized allopolyploid (M. peregrinus), and progenitor species (M. guttatus and M. luteus). We show that subgenome expression dominance occurs instantly following the hybridization of divergent genomes and significantly increases over generations. Additionally, CHH methylation levels are reduced in regions near genes and within TEs in the first-generation hybrid, intermediate in the resynthesized allopolyploid, and are repatterned differently between the dominant and recessive subgenomes in the natural allopolyploid. Subgenome differences in levels of TE methylation mirror the increase in expression bias observed over the generations following hybridization. These findings provide important insights into genomic and epigenomic shock that occurs following hybridization and polyploid events and may also contribute to uncovering the mechanistic basis of heterosis and subgenome dominance

A Likelihood Ratio Test for Changes in Homeolog Expression Bias

Background Gene duplications are a major source of raw material for evolution and a likely contributor to the diversity of life on earth. Duplicate genes (i.e., homeologs, in the case of a whole genome duplication) may retain their ancestral function, sub- or neofunctionalize, or be lost entirely. A primary way that duplicate genes evolve new functions is by altering their expression patterns. Comparing the expression patterns of duplicate genes gives clues as to whether any of these evolutionary processes have occurred. Results We develop a likelihood ratio test for the analysis of the expression ratios of duplicate genes across two conditions (e.g., tissues). We demonstrate an application of this test by comparing homeolog expression patterns of 1448 homeologous gene pairs using RNA-seq data generated from leaves and petals of an allotetraploid monkeyflower (Mimulus luteus). We assess the sensitivity of this test to different levels of homeolog expression bias and compare the method to several alternatives. Conclusions The likelihood ratio test derived here is a direct, transparent, and easily implemented method for detecting changes in homeolog expression bias that outperforms alternative approaches. While our method was derived with homeolog analysis in mind, this method can be used to analyze changes in the ratio of expression levels between any two genes in any two conditions

Zoowiki : un proyecto de colaboración interdepartamental

La presente comunicación presenta los resultados de un proyecto de innovación docente, desarrollado en el seno de la Facultad de Biología, con la colaboración de profesorado de la Facultad de Ciencias de la Educación, en el que han participado más de 200 alumnos y un total de 10 profesores (adscritos a los Departamentos de Fisiología y Zoología, y Didáctica y Organización Educativa, respectivamente) durante el curso académico 2010-11. Bajo la premisa: “Facilitando el aprendizaje entre iguales”, se ha llevado a cabo el estudio, planteándonos entre otros objetivos, no sólo hacer más consciente al alumnado de que es responsable de su propio aprendizaje, sino también la necesidad de motivación y mejora del rendimiento académico del alumnado. Para ello y teniendo en cuenta la metodología de aprendizaje entre iguales, se han creado grupos de expertos en distintas temáticas en la asignatura de Zoología, culminando el trabajo desarrollado en la confección de una wiki: Zoowiki http://proyectodezoologia.wikispaces.com/This paper presents the results of a teaching innovation project, developed within the Faculty of Biology, in collaboration with faculty at the Faculty of Education, which involved over 200 students and a total 10 teachers (assigned to the Departments of Physiology and Zoology, and Teaching and Educational Organization, respectively) during the academic year 2010-11. Under the premise: "Facilitating peer learning, " has carried out the study, posing among other objectives, to make the students more aware of who is responsible for their own learning ... but also the need for motivation and performance improvement academic students. For this and taking into account the methodology of peer learning groups have been established in different thematic expert in the subject of Zoology, culminating in the work developed in the preparation of a wiki: Zoowiki (http://proyectodezoologia.wikispaces.com/)

The Regulatory Network for Petal Anthocyanin Pigmentation is Shaped by the MYB5a/NEGAN Transcription Factor in Mimulus

Much of the visual diversity of angiosperms is due to the frequent evolution of novel pigmentation patterns in flowers. The gene network responsible for anthocyanin pigmentation, in particular, has become a model for investigating how genetic changes give rise to phenotypic innovation. In the monkeyflower genus Mimulus, an evolutionarily recent gain of petal lobe anthocyanin pigmentation in M. luteus var. variegatus was previously mapped to genomic region pla2. Here, we use sequence and expression analysis, followed by transgenic manipulation of gene expression, to identify MYB5a—orthologous to the NEGAN transcriptional activator from M. lewisii—as the gene responsible for the transition to anthocyanin-pigmented petals in M. l. variegatus. In other monkeyflower taxa, MYB5a/NEGAN is part of a reaction-diffusion network that produces semi-repeating spotting patterns, such as the array of spots in the nectar guides of both M. lewisii and M. guttatus. Its co-option for the evolution of an apparently non-patterned trait—the solid petal lobe pigmentation of M. l. variegatus—illustrates how reaction-diffusion can contribute to evolutionary novelty in non-obvious ways. Transcriptome sequencing of a MYB5a RNAi line of M. l. variegatus reveals that this genetically simple change, which we hypothesize to be a regulatory mutation in cis to MYB5a, has cascading effects on gene expression, not only on the enzyme-encoding genes traditionally thought of as the targets of MYB5a but also on all of its known partners in the anthocyanin regulatory network

Quantum Cosmology of Kantowski-Sachs like Models

The Wheeler-DeWitt equation for a class of Kantowski-Sachs like models is completely solved. The generalized models include the Kantowski-Sachs model with cosmological constant and pressureless dust. Likewise contained is a joined model which consists of a Kantowski-Sachs cylinder inserted between two FRW half--spheres. The (second order) WKB approximation is exact for the wave functions of the complete set and this facilitates the product structure of the wave function for the joined model. In spite of the product structure the wave function can not be interpreted as admitting no correlations between the different regions. This problem is due to the joining procedure and may therefore be present for all joined models. Finally, the {s}ymmetric {i}nitial {c}ondition (SIC) for the wave function is analyzed and compared with the ``no bouindary'' condition. The consequences of the different boundary conditions for the arrow of time are briefly mentioned.Comment: 21 pages, uses LaTeX2e, epsf.sty and float.sty, three figures (50 kb); changes: one figure added, new interpretation of quantizing procedure for the joined model and many minor change