196,460 research outputs found
Agents in Bioinformatics
No full textThe scope of the Technical Forum Group (TFG) on Agents in Bioinformatics (BIOAGENTS) was to inspire collaboration between the agent and bioinformatics communities with the aim of creating an opportunity to propose a different (agent-based) approach to the development of computational frameworks both for data analysis in bioinformatics and for system modelling in computational biology. During the day, the participants examined the future of research on agents in bioinformatics primarily through 12 invited talks selected to cover the most relevant topics. From the discussions, it became clear that there are many perspectives to the field, ranging from bio-conceptual languages for agent-based simulation, to the definition of bio-ontology-based declarative languages for use by information agents, and to the use of Grid agents, each of which requires further exploration. The interactions between participants encouraged the development of applications that describe a way of creating agent-based simulation models of biological systems, starting from an hypothesis and inferring new knowledge (or relations) by mining and analysing the huge amount of public biological data. In this report we summarise and reflect on the presentations and discussions
Epileptic seizures can be anticipated by geometric-topological entropy analysis
No full textEpilepsy is a complex brain disorder characterized by an hypersynchronous activity of neural ensemble in the brain. Nowadays electroencephalography (EEG) is the golden stan- dard for studying, monitoring and diagnosing epilepsy. Signals (time series), recorded by EEG, represent a description of the dynamics of the brain. Epilepsy is an emergent behavior given by a phase transition between a non-epileptic state (pre-ictal state) and an epileptic one (ictal state) of the neural hypergraph [1-2]. Traditional linear techniques applied to EEG show some limitation to identify these transitions while the non-linear ones seem to be more promising. The understanding of the underlying mechanisms of ictogenesis and propagation requires a suitable formal method to compute the model that supports the anticipation of ictal states. Recently, Topological Data Analysis and topological entropy [3-4], the so-called persistent entropy, are proven to be encouraging for distinguishing healthy from unhealthy patients by showing numerical evidence of the occurrence of phase transitions. We extend the previous work by providing a theoretical justification, based on statistical indexes (skewness and kurtosis), persistent entropy and topological invariants (Betti numbers), of the preliminary numerical results which describe the occurrence of a phase transition; moreover, we also intend to investigate the role of geometric entropy in quantifying the complexity of the networks since a change of complexity is also an indicator of a phase transition [5].
References
1. Varela F.J.; Naturalizing Phenomenology: Issues in Contemporary Phenomenology and Cognitive Science Edited by Jean, Petitot, Francisco J. Varela, Bernard Pachoud abd Jean-Michel Roy Stanford University Press, Stanford Chapter 9, pp.266-329
2. Piangerelli M.; Merelli E.; RNN-based Model for Self-adaptive Systems - The Emer- gence of Epilepsy in the Human Brain. IJCCI (NCTA).2014: 356-361
3. Merelli E.; Piangerelli M.; Rucco M.; Toller D.; A topological approach for multivariate time series characterization: the epileptic brain.2015
4. Rucco M.; Castiglione F.; Merelli E.; Pettini M.; Characterization of idiotypic immune network through Persistent Entropy. In Proc. Complex2015
5. Franzosi R.; Felice D.; Mancini M.; Pettini M.; A geometric entropy detecting the Erdös-Rényi phase transition. EPL.201
A Loop Grammar to Understand the roles of miRNAs in the Tumor Cell
No full textA miRNA is a small non-coding RNA molecule that regulates gene expression. Current studies showed that miRNAs may function both as oncogenes and as tumor suppressors, but not revealed the precise conditions that cause miRNAs to alter gene expression of the cancer cells. In this study, we introduce a context-free grammar, Loop Grammar, that formalizes the primary and secondary structure as a composition of loops, corresponding to concatenation or nesting of hairpins. We also formalize the concatenation and nesting on fatgraphs, oriented surfaces with boundary, and we define a Surface Loop Grammar, whose algebraic expressions uniquely identify such surfaces associated to given RNA structures. The Loop Grammar has been used to model tumor and healthy miRNAs of the mir-515 family, and we observed that the mutations of elements of primary structure involved in loops formation changed the secondary structure of tumor miRNAs. The Surface Loop Grammar is useful to classify RNA structures in terms of loops and relations among them.
References:
1) Peng, Y., Croce, C. M. The role of MicroRNAs in human cancer. Signal transduction and targeted
therapy, 2016, 1, 15004.
2) Penner, R.C., Knudsen, M., Wiuf, C., Andersen, J.E., Fatgraph models of proteins. Communications on Pure and Applied Mathematics, 2010, 63(10), 1249–1297
3) Quadrini, M., Culmone, R., Merelli, E.: Topological Classification of RNA Structures via Intersection Graph. In: International Conference on Theory and Practice of Natural Computing, Springer, 2017, 203–215
4) Quadrini, M., Merelli, E.: Loop-loop interaction metrics on RNA secondary structures with pseudoknotsth International Conference on Bioinformatics Models, Methods and Algorithms, Proceedings; Part of 11th International Joint Conference on Biomedical Engineering Systems and Technologies, BIOSTEC 2018 3, 2018
Shape Calculus: Timed Operational Semantics and Well-Formedness
No full textExtended version, including proofs, of Bartocci, E.; Cacciagrano, D. R.; Di Berardini, M. R.; Merelli, E. & Tesei, L. Timed Operational Semantics and Well-formedness of Shape Calculus. Scientific Annals of Computer Science, 20(1):33-52, 201
Validating MAS simulation models with mutation
No full textA key reason for choosing agent-based simulation of a biological system over other kinds of simulation model is the potential for structural as well as behavioral correspondence between the simulation model and the modeled system. This correspondence both demands and makes possible new kinds of model validation. Model fidelity can be evaluated by introducing seeded faults that correspond to known or hypothesized mutations, thus tying software validation to biological mutation analysis. The approach is illustrated by application to two implementations of an agent-based model of carbohydrate oxidation in a cell. © 2007 - IOS Press and the authors
Environmental factors and Autism Spectrum Disorder
No full textMultiple observations indicate that environmental and epigenetic factors play an important role in the emergence of Autism Spectrum Disorder (ASD). Growing ASD incidence rates, the incomplete penetrance of many rare variants linked to autism, and the increased exposure to environmental contaminants, all strongly support the role of Gene x Environment interactions in a substantial fraction of autistic patients. Within this framework, genetically susceptible individuals exposed to detrimental environmental factors at critical times during neurodevelopment, might undergo disrupted brain morphogenesis, neuronal connectivity, and synaptic functioning consequently yielding ASD. Several teratogenic drugs and prenatal viral infections are able to cause autism in humans, as supported by case reports, cohort studies and animal models. Moreover recent studies are showing that some newly identified potential neurotoxicants may negatively affect developmental trajectories, leading to altered cognitive, attentive, behavioral and motor performance, as well as to systemic abnormalities frequently seen in autistic individuals. A variety of mechanisms is potentially involved, ranging from oxidative and inflammatory brain damage to altered gene expression and impaired signal transduction. More research is needed to thoroughly investigate the effects of these compounds on neurodevelopment, to validate their involvement specifically in ASD, to study Gene x Environment interactions in potentially susceptible individuals and to plan targeted prevention strategies
Environmental Factors in the Onset of Autism Spectrum Disorder
No full textAutism Spectrum Disorder (ASD) is a heterogeneous clinical condition, whose prevalence has grown considerably during the last decade. Genetic factors are thought to underpin the disorder, but common genetic variants and epigenetic mechanisms have been increasingly called into question for the majority of ASD cases. Growing prenatal exposure to new environmental toxicants has been shown to potentially affect brain development, leading to altered cognitive, social, attentive, behavioral and motor performance. Both epidemiological evidence and mechanistic studies assessing oxidative stress, neuroinflammation, epigenetic alterations and impaired signal transduction, all observed following neurotoxicant exposure, indeed lend biological plausibility to Gene x Environment interactions, whereby environmental toxicants interacting additively or synergistically with genetic liability, can push prenatal neurodevelopmental processes over the threshold for postnatal ASD expression. Research on environmental contributions to ASD and on specific Gene x Environment interaction models ultimately aims at defining targeted preventive strategies
Process-based modelling towards the simulation of long-distance electrodynamic interactions of biomolecules
No full textOur work is focussed on the computational study of the molecular interactions in biological systems. We hypothesise the use of process algebras to highlight the relation between the complexity of the functions carried out by a biological entity and the type of interactions tying the elementary units that compose its structure. This approach is intended to define predictive models able to generate new knowledge, on the system itself, complementary to the one obtained via empirical methods.
We investigated the way in which the interactions between nucleotides determine the three-dimensional conformation of RNAs and hence their functions. With the aid of formal models based on process algebras, we compared the folding process of proteins with the one performed by RNAs. We formally proved the existence of an abstraction level in which these two kinds of processes show a congruence in their behaviour. Such result allows us to identify and model the distinguishing features of the studied biological processes only on the basis of the known properties of the interactions that bind the nucleotides (in RNAs) and the amino acids (in proteins). This was possible thanks to the expressiveness of a specific process algebra, the Milner’s CCS (Calculus of Communicating Systems)1.
We are also working on an application of the proposed modelling approach to the studies carried out at the CPT (Centre de Physique Théorique, Aix-Marseille University), on the long-distance electrodynamic interactions of biomolecules2. The main idea is to develop a simulator able to solve the problem of the possible interpenetrations of the represented molecules. It would be also intended to yield information on the temporal evolution of the molecular interactions.
Applications of our approach in modelling the processes involved in the gene expression would allow the identification of mutations in human gene pathologies; on the other hand, simulations of protein interactions would be the basis of in-silico studies of the formation of protein aggregates, like amyloid plaques in neurodegenerative diseases.
References:
1) Milner, R. Communication and Concurrency; Upper Saddle River, 1989, NJ, USA: Prentice-Hall, Inc.
2) Gori, M. et al. Investigation of Brownian diffusion and long-distance electrodynamic interactions of biomolecules. Noise and Fluctuations (ICNF), 2015, International Conference on. IEEE, pp. 1 – 4
Les politiques des temps urbains: l'expérience italienne
No full textIl saggio analizza l’esperienza italiana delle “politiche temporali urbane”, cioè quegli interventi di policy - sostenuti in primis dal governo locale della città - volti a ridefinire il funzionamento temporale dei servizi per una "città-amica-di-chi-ci-vive", che risponda alle nuove e diversificate esigenze dei cittadini, a cominciare dalle donne. Queste ne hanno fatto, tra la fine degli anni '80 e l'inizio del decennio successivo, proposte progettuali e pratiche politiche tese ad ampliare la qualità della vita agendo per un miglioramento della qualità dei servizi a cominciare da quelli pubblici, o di interesse pubblico, e per la qualità (in molti casi) dei luoghi fisici, degli aspetti urbanistici e dell'ambiente.Alla prospettiva delle “politiche temporali urbane” ha rivolto il suo sguardo anche il legislatore statale. L’ultima parte della legge n. 53 del 2000 (e successive modifiche ed integrazioni) apre infatti il suo raggio d’azione ai «tempi delle città», giusta la rubrica di cui al Capo VII
Process-based Modelling of RNA and Protein Interactions: A Formal Approach
No full textOur work is focussed on the computational study of the molecular interactions in biological systems. We hypothesise the use of process algebras to highlight the relation between the complexity of the functions carried out by a biological entity and the type of interactions tying the elementary units that compose its structure. This approach is intended to define predictive models able to generate new knowledge, on the system itself, complementary to the one obtained via empirical methods.
We investigated the way in which the interactions between nucleotides determine the three-dimensional conformation of RNAs and hence their functions. With the aid of formal models based on process algebras, we compared the folding process of proteins with the one performed by RNAs. We formally proved the existence of an abstraction level in which these two kinds of processes show a congruence in their behaviour. Such result allows us to identify and model the distinguishing features of the studied biological processes only on the basis of the known properties of the interactions that bind the nucleotides (in RNAs) and the amino acids (in proteins). This was possible thanks to the expressiveness of a specific process algebra, the Milner’s CCS (Calculus of Communicating Systems)1. The formal demonstration of the existence of the above-described abstraction level has been provided in an article submitted for publication in a peer-reviewed journal2.
We are also working on an application of the proposed modelling approach to the studies carried out at the CPT (Centre de Physique Théorique, Aix-Marseille University) on the long-distance electrodynamic interactions of biomolecules3. The main idea is to develop a simulator able to solve the problem of the possible interpenetrations of the represented molecules by providing them with three-dimensional shapes that cannot cross each other. It would be also intended to yield information on the temporal evolution of the molecular interactions.
References:
1) Milner, R. Communication and Concurrency; Upper Saddle River, 1989, NJ, USA: Prentice-Hall, Inc.
2) Maestri, S.; Merelli, E. Process calculi may reveal the equivalence lying at the heart of RNA and proteins. 2018, Manuscript submitted for publication.
3) Gori, M. et al. Investigation of Brownian diffusion and long-distance electrodynamic interactions of biomolecules. Noise and Fluctuations (ICNF), 2015, International Conference on. IEEE, pp. 1 – 4
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