5,176 research outputs found
Flexible RNA design under structure and sequence constraints using formal languages
The problem of RNA secondary structure design (also called inverse folding)
is the following: given a target secondary structure, one aims to create a
sequence that folds into, or is compatible with, a given structure. In several
practical applications in biology, additional constraints must be taken into
account, such as the presence/absence of regulatory motifs, either at a
specific location or anywhere in the sequence. In this study, we investigate
the design of RNA sequences from their targeted secondary structure, given
these additional sequence constraints. To this purpose, we develop a general
framework based on concepts of language theory, namely context-free grammars
and finite automata. We efficiently combine a comprehensive set of constraints
into a unifying context-free grammar of moderate size. From there, we use
generic generic algorithms to perform a (weighted) random generation, or an
exhaustive enumeration, of candidate sequences. The resulting method, whose
complexity scales linearly with the length of the RNA, was implemented as a
standalone program. The resulting software was embedded into a publicly
available dedicated web server. The applicability demonstrated of the method on
a concrete case study dedicated to Exon Splicing Enhancers, in which our
approach was successfully used in the design of \emph{in vitro} experiments.Comment: ACM BCB 2013 - ACM Conference on Bioinformatics, Computational
Biology and Biomedical Informatics (2013
COMPUTER SIMULATION AND COMPUTABILITY OF BIOLOGICAL SYSTEMS
The ability to simulate a biological organism by employing a computer is related to the
ability of the computer to calculate the behavior of such a dynamical system, or the "computability" of the system.* However, the two questions of computability and simulation are not equivalent. Since the question of computability can be given a precise answer in terms of recursive functions, automata theory and dynamical systems, it will be appropriate to consider it first. The more elusive question of adequate simulation of biological systems by a computer will be then addressed and a possible connection between the two answers given will be considered. A conjecture is formulated that suggests the possibility of employing an algebraic-topological, "quantum" computer (Baianu, 1971b)
for analogous and symbolic simulations of biological systems that may include chaotic processes that are not, in genral, either recursively or digitally computable. Depending on the biological network being modelled, such as the Human Genome/Cell Interactome or a trillion-cell Cognitive Neural Network system, the appropriate logical structure for such simulations might be either the Quantum MV-Logic (QMV) discussed in recent publications (Chiara, 2004, and references cited therein)or Lukasiewicz Logic Algebras that were shown to be isomorphic to MV-logic algebras (Georgescu et al, 2001)
Lazy Probabilistic Model Checking without Determinisation
The bottleneck in the quantitative analysis of Markov chains and Markov
decision processes against specifications given in LTL or as some form of
nondeterministic B\"uchi automata is the inclusion of a determinisation step of
the automaton under consideration. In this paper, we show that full
determinisation can be avoided: subset and breakpoint constructions suffice. We
have implemented our approach---both explicit and symbolic versions---in a
prototype tool. Our experiments show that our prototype can compete with mature
tools like PRISM.Comment: 38 pages. Updated version for introducing the following changes: -
general improvement on paper presentation; - extension of the approach to
avoid full determinisation; - added proofs for such an extension; - added
case studies; - updated old case studies to reflect the added extensio
Probabilistic Bisimulation: Naturally on Distributions
In contrast to the usual understanding of probabilistic systems as stochastic
processes, recently these systems have also been regarded as transformers of
probabilities. In this paper, we give a natural definition of strong
bisimulation for probabilistic systems corresponding to this view that treats
probability distributions as first-class citizens. Our definition applies in
the same way to discrete systems as well as to systems with uncountable state
and action spaces. Several examples demonstrate that our definition refines the
understanding of behavioural equivalences of probabilistic systems. In
particular, it solves a long-standing open problem concerning the
representation of memoryless continuous time by memory-full continuous time.
Finally, we give algorithms for computing this bisimulation not only for finite
but also for classes of uncountably infinite systems
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