Abstract: Prediction of perturbations after genetic manipulation
(especially gene knockout) is one of the important challenges in
systems biology. In this paper, a new algorithm is introduced that
integrates microarray data into the metabolic model. The algorithm
was used to study the change in the cell phenotype after knockout of
Gss gene in Escherichia coli BW25113. Algorithm implementation
indicated that gene deletion resulted in more activation of the
metabolic network. Growth yield was more and less regulating gene
were identified for mutant in comparison with the wild-type strain.
Abstract: This paper describes a novel approach for deriving
modules from protein-protein interaction networks, which combines
functional information with topological properties of the network.
This approach is based on weighted clustering coefficient, which
uses weights representing the functional similarities between the
proteins. These weights are calculated according to the semantic
similarity between the proteins, which is based on their Gene
Ontology terms. We recently proposed an algorithm for identification
of functional modules, called SWEMODE (Semantic WEights for
MODule Elucidation), that identifies dense sub-graphs containing
functionally similar proteins. The rational underlying this approach is
that each module can be reduced to a set of triangles (protein triplets
connected to each other). Here, we propose considering semantic
similarity weights of all triangle-forming edges between proteins. We
also apply varying semantic similarity thresholds between
neighbours of each node that are not neighbours to each other (and
hereby do not form a triangle), to derive new potential triangles to
include in module-defining procedure. The results show an
improvement of pure topological approach, in terms of number of
predicted modules that match known complexes.
Abstract: Mendelian Disease Genes represent a collection of single points of failure for the various systems they constitute. Such genes have been shown, on average, to encode longer proteins than 'non-disease' proteins. Existing models suggest that this results from the increased likeli-hood of longer genes undergoing mutations. Here, we show that in saturated mutagenesis experiments performed on model organisms, where the likelihood of each gene mutating is one, a similar relationship between length and the probability of a gene being lethal was observed. We thus suggest an extended model demonstrating that the likelihood of a mutated gene to produce a severe phenotype is length-dependent. Using the occurrence of conserved domains, we bring evidence that this dependency results from a correlation between protein length and the number of functions it performs. We propose that protein length thus serves as a proxy for protein cardinality in different networks required for the organism's survival and well-being. We use this example to argue that the collection of Mendelian Disease Genes can, and should, be used to study the rules governing systems vulnerability in living organisms.
Abstract: The goal of Gene Expression Analysis is to understand the processes that underlie the regulatory networks and pathways controlling inter-cellular and intra-cellular activities. In recent times microarray datasets are extensively used for this purpose. The scope of such analysis has broadened in recent times towards reconstruction of gene networks and other holistic approaches of Systems Biology. Evolutionary methods are proving to be successful in such problems and a number of such methods have been proposed. However all these methods are based on processing of genotypic information. Towards this end, there is a need to develop evolutionary methods that address phenotypic interactions together with genotypic interactions. We present a novel evolutionary approach, called Phenomic algorithm, wherein the focus is on phenotypic interaction. We use the expression profiles of genes to model the interactions between them at the phenotypic level. We apply this algorithm to the yeast sporulation dataset and show that the algorithm can identify gene networks with relative ease.
Abstract: Stochastic models of biological networks are well established in systems biology, where the computational treatment of such models is often focused on the solution of the so-called chemical master equation via stochastic simulation algorithms. In contrast to this, the development of storage-efficient model representations that are directly suitable for computer implementation has received significantly less attention. Instead, a model is usually described in terms of a stochastic process or a "higher-level paradigm" with graphical representation such as e.g. a stochastic Petri net. A serious problem then arises due to the exponential growth of the model-s state space which is in fact a main reason for the popularity of stochastic simulation since simulation suffers less from the state space explosion than non-simulative numerical solution techniques. In this paper we present transition class models for the representation of biological network models, a compact mathematical formalism that circumvents state space explosion. Transition class models can also serve as an interface between different higher level modeling paradigms, stochastic processes and the implementation coded in a programming language. Besides, the compact model representation provides the opportunity to apply non-simulative solution techniques thereby preserving the possible use of stochastic simulation. Illustrative examples of transition class representations are given for an enzyme-catalyzed substrate conversion and a part of the bacteriophage λ lysis/lysogeny pathway.
Abstract: Bioinformatics and computational biology involve
the use of techniques including applied mathematics,
informatics, statistics, computer science, artificial intelligence,
chemistry, and biochemistry to solve biological problems
usually on the molecular level. Research in computational
biology often overlaps with systems biology. Major research
efforts in the field include sequence alignment, gene finding,
genome assembly, protein structure alignment, protein structure
prediction, prediction of gene expression and proteinprotein
interactions, and the modeling of evolution. Various
global rearrangements of permutations, such as reversals and
transpositions,have recently become of interest because of their
applications in computational molecular biology. A reversal is
an operation that reverses the order of a substring of a permutation.
A transposition is an operation that swaps two adjacent
substrings of a permutation. The problem of determining the
smallest number of reversals required to transform a given
permutation into the identity permutation is called sorting by
reversals. Similar problems can be defined for transpositions
and other global rearrangements. In this work we perform a
study about some genome rearrangement primitives. We show
how a genome is modelled by a permutation, introduce some
of the existing primitives and the lower and upper bounds
on them. We then provide a comparison of the introduced
primitives.