4,856 research outputs found
Computational models for inferring biochemical networks
Biochemical networks are of great practical importance. The interaction of biological compounds in cells has been enforced to a proper understanding by the numerous bioinformatics projects, which contributed to a vast amount of biological information. The construction of biochemical systems (systems of chemical reactions), which include both topology and kinetic constants of the chemical reactions, is NP-hard and is a well-studied system biology problem. In this paper, we propose a hybrid architecture, which combines genetic programming and simulated annealing in order to generate and optimize both the topology (the network) and the reaction rates of a biochemical system. Simulations and analysis of an artificial model and three real models (two models and the noisy version of one of them) show promising results for the proposed method.The Romanian National Authority for Scientific Research, CNDI–UEFISCDI,
Project No. PN-II-PT-PCCA-2011-3.2-0917
Methods for protein complex prediction and their contributions towards understanding the organization, function and dynamics of complexes
Complexes of physically interacting proteins constitute fundamental
functional units responsible for driving biological processes within cells. A
faithful reconstruction of the entire set of complexes is therefore essential
to understand the functional organization of cells. In this review, we discuss
the key contributions of computational methods developed till date
(approximately between 2003 and 2015) for identifying complexes from the
network of interacting proteins (PPI network). We evaluate in depth the
performance of these methods on PPI datasets from yeast, and highlight
challenges faced by these methods, in particular detection of sparse and small
or sub- complexes and discerning of overlapping complexes. We describe methods
for integrating diverse information including expression profiles and 3D
structures of proteins with PPI networks to understand the dynamics of complex
formation, for instance, of time-based assembly of complex subunits and
formation of fuzzy complexes from intrinsically disordered proteins. Finally,
we discuss methods for identifying dysfunctional complexes in human diseases,
an application that is proving invaluable to understand disease mechanisms and
to discover novel therapeutic targets. We hope this review aptly commemorates a
decade of research on computational prediction of complexes and constitutes a
valuable reference for further advancements in this exciting area.Comment: 1 Tabl
Structure induction by lossless graph compression
This work is motivated by the necessity to automate the discovery of
structure in vast and evergrowing collection of relational data commonly
represented as graphs, for example genomic networks. A novel algorithm, dubbed
Graphitour, for structure induction by lossless graph compression is presented
and illustrated by a clear and broadly known case of nested structure in a DNA
molecule. This work extends to graphs some well established approaches to
grammatical inference previously applied only to strings. The bottom-up graph
compression problem is related to the maximum cardinality (non-bipartite)
maximum cardinality matching problem. The algorithm accepts a variety of graph
types including directed graphs and graphs with labeled nodes and arcs. The
resulting structure could be used for representation and classification of
graphs.Comment: 10 pages, 7 figures, 2 tables published in Proceedings of the Data
Compression Conference, 200
Object-Oriented Paradigms for Modelling Vascular\ud Tumour Growth: a Case Study
Motivated by a family of related hybrid multiscale models, we have built an object-oriented framework for developing and implementing multiscale models of vascular tumour growth. The models are implemented in our framework as a case study to highlight how object-oriented programming techniques and good object-oriented design may be used effectively to develop hybrid multiscale models of vascular tumour growth. The intention is that this paper will serve as a useful reference for researchers modelling complex biological systems and that these researchers will employ some of the techniques presented herein in their own projects
Hierarchy of protein loop-lock structures: a new server for the decomposition of a protein structure into a set of closed loops
HoPLLS (Hierarchy of protein loop-lock structures)
(http://leah.haifa.ac.il/~skogan/Apache/mydata1/main.html) is a web server that
identifies closed loops - a structural basis for protein domain hierarchy. The
server is based on the loop-and-lock theory for structural organisation of
natural proteins. We describe this web server, the algorithms for the
decomposition of a 3D protein into loops and the results of scientific
investigations into a structural "alphabet" of loops and locks.Comment: 11 pages, 4 figure
Accurate prediction of gene expression by integration of DNA sequence statistics with detailed modeling of transcription regulation
Gene regulation involves a hierarchy of events that extend from specific
protein-DNA interactions to the combinatorial assembly of nucleoprotein
complexes. The effects of DNA sequence on these processes have typically been
studied based either on its quantitative connection with single-domain binding
free energies or on empirical rules that combine different DNA motifs to
predict gene expression trends on a genomic scale. The middle-point approach
that quantitatively bridges these two extremes, however, remains largely
unexplored. Here, we provide an integrated approach to accurately predict gene
expression from statistical sequence information in combination with detailed
biophysical modeling of transcription regulation by multidomain binding on
multiple DNA sites. For the regulation of the prototypical lac operon, this
approach predicts within 0.3-fold accuracy transcriptional activity over a
10,000-fold range from DNA sequence statistics for different intracellular
conditions.Comment: 15 pages, 5 figure
Erratum: Signal propagation in proteins and relation to equilibrium fluctuations (PLoS Computational Biology (2007) 3, 9, (e172) DOI: 10.1371/journal.pcbi.0030172))
Elastic network (EN) models have been widely used in recent years for describing protein dynamics, based on the premise that the motions naturally accessible to native structures are relevant to biological function. We posit that equilibrium motions also determine communication mechanisms inherent to the network architecture. To this end, we explore the stochastics of a discrete-time, discrete-state Markov process of information transfer across the network of residues. We measure the communication abilities of residue pairs in terms of hit and commute times, i.e., the number of steps it takes on an average to send and receive signals. Functionally active residues are found to possess enhanced communication propensities, evidenced by their short hit times. Furthermore, secondary structural elements emerge as efficient mediators of communication. The present findings provide us with insights on the topological basis of communication in proteins and design principles for efficient signal transduction. While hit/commute times are information-theoretic concepts, a central contribution of this work is to rigorously show that they have physical origins directly relevant to the equilibrium fluctuations of residues predicted by EN models
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