Computing paths and cycles in biological interaction graphs

<p>Abstract</p> <p>Background</p> <p>Interaction graphs (signed directed graphs) provide an important qualitative modeling approach for Systems Biology. They enable the analysis of causal relationships in cellular networks and can even be useful for predicting qualitative aspects of systems dynamics. Fundamental issues in the analysis of interaction graphs are the enumeration of paths and cycles (feedback loops) and the calculation of shortest positive/negative paths. These computational problems have been discussed only to a minor extent in the context of Systems Biology and in particular the shortest signed paths problem requires algorithmic developments.</p> <p>Results</p> <p>We first review algorithms for the enumeration of paths and cycles and show that these algorithms are superior to a recently proposed enumeration approach based on elementary-modes computation. The main part of this work deals with the computation of shortest positive/negative paths, an NP-complete problem for which only very few algorithms are described in the literature. We propose extensions and several new algorithm variants for computing either exact results or approximations. Benchmarks with various concrete biological networks show that exact results can sometimes be obtained in networks with several hundred nodes. A class of even larger graphs can still be treated exactly by a new algorithm combining exhaustive and simple search strategies. For graphs, where the computation of exact solutions becomes time-consuming or infeasible, we devised an approximative algorithm with polynomial complexity. Strikingly, in realistic networks (where a comparison with exact results was possible) this algorithm delivered results that are very close or equal to the exact values. This phenomenon can probably be attributed to the particular topology of cellular signaling and regulatory networks which contain a relatively low number of negative feedback loops.</p> <p>Conclusion</p> <p>The calculation of shortest positive/negative paths and cycles in interaction graphs is an important method for network analysis in Systems Biology. This contribution draws the attention of the community to this important computational problem and provides a number of new algorithms, partially specifically tailored for biological interaction graphs. All algorithms have been implemented in the <it>CellNetAnalyzer </it>framework which can be downloaded for academic use at <url>http://www.mpi-magdeburg.mpg.de/projects/cna/cna.html</url>.</p

Clearing Contamination in Large Networks

In this work, we study the problem of clearing contamination spreading through a large network where we model the problem as a graph searching game. The problem can be summarized as constructing a search strategy that will leave the graph clear of any contamination at the end of the searching process in as few steps as possible. We show that this problem is NP-hard even on directed acyclic graphs and provide an efficient approximation algorithm. We experimentally observe the performance of our approximation algorithm in relation to the lower bound on several large online networks including Slashdot, Epinions and Twitter. The experiments reveal that in most cases our algorithm performs near optimally

Complexity of fixed point counting problems in Boolean Networks

A Boolean network (BN) with $n$ components is a discrete dynamical system described by the successive iterations of a function $f:\{0,1\}^n \to \{0,1\}^n$. This model finds applications in biology, where fixed points play a central role. For example, in genetic regulations, they correspond to cell phenotypes. In this context, experiments reveal the existence of positive or negative influences among components: component $i$ has a positive (resp. negative) influence on component $j$ meaning that $j$ tends to mimic (resp. negate) $i$. The digraph of influences is called signed interaction digraph (SID), and one SID may correspond to a large number of BNs (which is, in average, doubly exponential according to $n$). The present work opens a new perspective on the well-established study of fixed points in BNs. When biologists discover the SID of a BN they do not know, they may ask: given that SID, can it correspond to a BN having at least/at most $k$ fixed points? Depending on the input, we prove that these problems are in $\textrm{P}$ or complete for $\textrm{NP}$, $\textrm{NP}^{\textrm{NP}}$, \textrm{NP}^{\textrm{#P}} or $\textrm{NEXPTIME}$. In particular, we prove that it is $\textrm{NP}$-complete (resp. $\textrm{NEXPTIME}$-complete) to decide if a given SID can correspond to a BN having at least two fixed points (resp. no fixed point).Comment: 43 page

An extensive English language bibliography on graph theory and its applications, supplement 1

Graph theory and its applications - bibliography, supplement

An extensive English language bibliography on graph theory and its applications

Bibliography on graph theory and its application