Graphs in molecular biology

Graph theoretical concepts are useful for the description and analysis of interactions and relationships in biological systems. We give a brief introduction into some of the concepts and their areas of application in molecular biology. We discuss software that is available through the Bioconductor project and present a simple example application to the integration of a protein-protein interaction and a co-expression network

Principal manifolds and graphs in practice: from molecular biology to dynamical systems

We present several applications of non-linear data modeling, using principal manifolds and principal graphs constructed using the metaphor of elasticity (elastic principal graph approach). These approaches are generalizations of the Kohonen's self-organizing maps, a class of artificial neural networks. On several examples we show advantages of using non-linear objects for data approximation in comparison to the linear ones. We propose four numerical criteria for comparing linear and non-linear mappings of datasets into the spaces of lower dimension. The examples are taken from comparative political science, from analysis of high-throughput data in molecular biology, from analysis of dynamical systems.Comment: 12 pages, 9 figure

Error Graphs and the Reconstruction of Elements in Groups

Packing and covering problems for metric spaces, and graphs in particular, are of essential interest in combinatorics and coding theory. They are formulated in terms of metric balls of vertices. We consider a new problem in graph theory which is also based on the consideration of metric balls of vertices, but which is distinct from the traditional packing and covering problems. This problem is motivated by applications in information transmission when redundancy of messages is not sufficient for their exact reconstruction, and applications in computational biology when one wishes to restore an evolutionary process. It can be defined as the reconstruction, or identification, of an unknown vertex in a given graph from a minimal number of vertices (erroneous or distorted patterns) in a metric ball of a given radius r around the unknown vertex. For this problem it is required to find minimum restrictions for such a reconstruction to be possible and also to find efficient reconstruction algorithms under such minimal restrictions. In this paper we define error graphs and investigate their basic properties. A particular class of error graphs occurs when the vertices of the graph are the elements of a group, and when the path metric is determined by a suitable set of group elements. These are the undirected Cayley graphs. Of particular interest is the transposition Cayley graph on the symmetric group which occurs in connection with the analysis of transpositional mutations in molecular biology. We obtain a complete solution of the above problems for the transposition Cayley graph on the symmetric group.Comment: Journal of Combinatorial Theory A 200

Toll Based Measures for Dynamical Graphs

Biological networks are one of the most studied object in computational biology. Several methods have been developed for studying qualitative properties of biological networks. Last decade had seen the improvement of molecular techniques that make quantitative analyses reachable. One of the major biological modelling goals is therefore to deal with the quantitative aspect of biological graphs. We propose a probabilistic model that suits with this quantitative aspects. Our model combines graph with several dynamical sources. It emphazises various asymptotic statistical properties that might be useful for giving biological insightsComment: 11 page

Analysis of Three-Dimensional Protein Images

A fundamental goal of research in molecular biology is to understand protein structure. Protein crystallography is currently the most successful method for determining the three-dimensional (3D) conformation of a protein, yet it remains labor intensive and relies on an expert's ability to derive and evaluate a protein scene model. In this paper, the problem of protein structure determination is formulated as an exercise in scene analysis. A computational methodology is presented in which a 3D image of a protein is segmented into a graph of critical points. Bayesian and certainty factor approaches are described and used to analyze critical point graphs and identify meaningful substructures, such as alpha-helices and beta-sheets. Results of applying the methodologies to protein images at low and medium resolution are reported. The research is related to approaches to representation, segmentation and classification in vision, as well as to top-down approaches to protein structure prediction.Comment: See http://www.jair.org/ for any accompanying file

Solving Hard Computational Problems Efficiently: Asymptotic Parametric Complexity 3-Coloring Algorithm

Many practical problems in almost all scientific and technological disciplines have been classified as computationally hard (NP-hard or even NP-complete). In life sciences, combinatorial optimization problems frequently arise in molecular biology, e.g., genome sequencing; global alignment of multiple genomes; identifying siblings or discovery of dysregulated pathways.In almost all of these problems, there is the need for proving a hypothesis about certain property of an object that can be present only when it adopts some particular admissible structure (an NP-certificate) or be absent (no admissible structure), however, none of the standard approaches can discard the hypothesis when no solution can be found, since none can provide a proof that there is no admissible structure. This article presents an algorithm that introduces a novel type of solution method to "efficiently" solve the graph 3-coloring problem; an NP-complete problem. The proposed method provides certificates (proofs) in both cases: present or absent, so it is possible to accept or reject the hypothesis on the basis of a rigorous proof. It provides exact solutions and is polynomial-time (i.e., efficient) however parametric. The only requirement is sufficient computational power, which is controlled by the parameter $\alpha\in\mathbb{N}$. Nevertheless, here it is proved that the probability of requiring a value of $\alpha>k$ to obtain a solution for a random graph decreases exponentially: $P(\alpha>k) \leq 2^{-(k+1)}$, making tractable almost all problem instances. Thorough experimental analyses were performed. The algorithm was tested on random graphs, planar graphs and 4-regular planar graphs. The obtained experimental results are in accordance with the theoretical expected results.Comment: Working pape

Dynamic load balancing for the distributed mining of molecular structures

In molecular biology, it is often desirable to find common properties in large numbers of drug candidates. One family of methods stems from the data mining community, where algorithms to find frequent graphs have received increasing attention over the past years. However, the computational complexity of the underlying problem and the large amount of data to be explored essentially render sequential algorithms useless. In this paper, we present a distributed approach to the frequent subgraph mining problem to discover interesting patterns in molecular compounds. This problem is characterized by a highly irregular search tree, whereby no reliable workload prediction is available. We describe the three main aspects of the proposed distributed algorithm, namely, a dynamic partitioning of the search space, a distribution process based on a peer-to-peer communication framework, and a novel receiverinitiated load balancing algorithm. The effectiveness of the distributed method has been evaluated on the well-known National Cancer Institute’s HIV-screening data set, where we were able to show close-to linear speedup in a network of workstations. The proposed approach also allows for dynamic resource aggregation in a non dedicated computational environment. These features make it suitable for large-scale, multi-domain, heterogeneous environments, such as computational grids