Computation and Synchronisation in Complex Dynamical Networks

Eihab Bashier Mohammed

Supervisor:

Dr. Gareth Witten. (University of Cape Town)

An essay submitted in partial fulllment of the requirements for AIMS Postgraduate Diploma in Mathematical Sciences.

May, 2004

Acknowledgement

I am very grateful to Dr. Gareth, who has been helpful to me; Prof. Wesley Kotze, who gave me a part of his valuable time; Dr. Mike Pickles, who stood behind me until I completed this work; and to all AIMS sta.

Dedication

To my parents, my family and all my colleagues; I dedicate this work.

Abstract In this short essay, we aim to explain how do the researchers use the concepts from graph theory to study the networks of complex systems, where the structure of these networks and the dynamics of its nodes are the factors which determine the behaviour of the system at all. We explained that, a structure of some network, can be characterized by three important measures, and play the main role in determininning the topological properties of that network. Another important task, is how coupling of the nodes of the network which themselves are complex systems can aect the global behaviour of the network, like achieving synchronisation. The researchers aim to know how do the topology of the network and the dynamics of its nodes together, aect the long-term behaviour of the network. Hence, mathematical models were written to describe the dynamics of these networks. These models can not be solved analytically, hence the computational methods are used to nd numerical solutions for these models. The problem with the computaions in large complex networks, and in particular the biological networks is that, their behaviour is unpredictable. We took as example the genetic regulatory networks as an application to the dynamical complex networks, and discussed briey some of the methods to model them, and some of the results obtained by these methods.

Contents
Abstract 1 Introduction 1.1 What is a Network? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.2 What is a Complex Network? . . . . . . . . . . . . . . . . . . . . . . . . . 1.3 Dynamics on Complex Systems . . . . . . . . . . . . . . . . . . . . . . . . 1 4 4 6 8

1.4 Synchronisation in Networks of Complex Systems . . . . . . . . . . . . . . 10 2 Structures of Complex Networks 12

2.1 Denitions and Preliminaries . . . . . . . . . . . . . . . . . . . . . . . . . . 12 2.2 Random Networks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14 2.3 Regular Networks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 2.4 Small-World Networks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 2.5 Scale-Free Networks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 2.6 Similarities and Contrasts . . . . . . . . . . . . . . . . . . . . . . . . . . . 24 3 Dynamics and Synchrony 26

3.1 Denitions and Basic Concepts . . . . . . . . . . . . . . . . . . . . . . . . 26 3.2 Synchronisation in Regular Networks . . . . . . . . . . . . . . . . . . . . . 28 3.3 Synchronisation in Small-World Networks . . . . . . . . . . . . . . . . . . 30

3.4 Synchronisation in Scale-Free Networks . . . . . . . . . . . . . . . . . . . . 31 3.4.1 Stability Analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31 2

3.4.2

Robustness and Fragility of Synchronisation: . . . . . . . . . . . . . 32 35

4 Application: Genetic Regulatory Networks 4.1 4.2 Background: Regulatory Networks

. . . . . . . . . . . . . . . . . . . . . . 35

Modelling Genetic Regulatory Networks . . . . . . . . . . . . . . . . . . . 39 4.2.1 4.2.2 4.2.3 Boolean Network Model . . . . . . . . . . . . . . . . . . . . . . . . 39 Dierential Equations Models . . . . . . . . . . . . . . . . . . . . . 41 The Articial Genomic Model . . . . . . . . . . . . . . . . . . . . . 44 46 48

5 Discussions Bibliography

Chapter 1 Introduction
1.1 What is a Network?

A network can be represented as a graph consisting of a nite set of vertices (nodes) V , and a nite set of edges (links) E. A graph is often denoted as a pair G(V, E), where V is the set of vertices, V = {v1 , v2 , . . . , vN }, and E the set of edges, is a subset of the Cartisean product V V . The graph can be connected or disconnected, directed or undirected and weighted or unweighted. We will assume always that the graph is connected, and hence, if k denotes the number of edges, then k must satisfy the inequality 1 < log(N) < k < N .

Networks observed in reality are called real-world networks. They include: World Wide Web (WWW): the nodes are web pages, and the edges are the hyper-links. WWW is a directed network (Albert and Barabsi[1]). a Internet: The nodes are routers and the edges are the physical connections between them. The Internet is an undirected network (Albert and Barabsi[1]). a Cellular networks: the substrates (ATP, ADP, G20) are the nodes, and the edges represent the predominaly directed chemical reactions in which these substrates can participate. 4

 Ecological networks or food webs: the nodes are species, and the edges represent the predator-pray relationships among them. Ecological networks are directed networks [3]. Protein folding: dierent states of single protein are represented by nodes. Conformations are linked if they can be obtained from each other by an elementary move. This is undirected network. Movie actor collaboration network: The nodes are the actors and two nodes are connected if two actors have acted in a movie together. This is undirected network[33]. Power networks: the nodes are generators, transformers and substations, and the edges are high-voltage transmission lines[33]. Neural networks: The nodes are the neurons, and two neurons are joined together, if connected by either synapse or gap-junction[33]. The adjacency matrix R(G) is dened to be: R(G) = [rij ] where, 1 (v , v ) E i j rij = 0 otherwise For an undirected graph G, the adjacency matrix R(G) is symmetric (rij = rji, i, j {1, 2, . . . , N}), and the diagonal elements of R(G) are zeros. Hence the lower or upper triangular matrix of R(G) is sucient for a complete description of the graph. The number of edges connected to some node is called its degree.

A complex system is any system which featuring a large number of interacting components, whose aggregate activity is nonlinear, and typically exhibits hierarchical selforganisation under selective pressures[19]. The network topology means the conguration of the connections between its nodes.

1.2

What is a Complex Network?

A complex network is a network with complex topology, whose nodes may be the elements of a complex system, and whose edges represent the interactions between them, and many complex systems can be described in terms of networks of interacting units. Why network anatomy is so important to characterise?[25]. The basic properties of very large networks, are mainly determined by the way the nodes are connected, i.e. the topology of a networks, aects its function, like the spread of information and disease in social networks. Therefore, much recent research work on complex networks has focused on the structural topology of these networks. Networks grow and evolve by local events, such as the addition of new nodes and links, or rewiring of links from one node to another. The complexity of a network, comes from two dierent sources: 1. the topology of the network (complexity due to the topology). 2. the dynamics of its complex nodes (complexity due to the dynamics). For over a century, modelling of physical as well as non-physical systems and processes has been performed under an implicit assumption that, the interaction patterns among the individuals of the underlying system or process can be embedded onto a regular and perhaps universal structure such as a Euclidean lattice.[30] The two mathematicians Erds and Rnyi, described a network with complex topology o e by random graph. For their network, they assumed that, the connections between the nodes occur in random, and the degree P (k) that gives the probability for some given node to be linked to k other nodes is a Poissonian. However, the Erds-Rnyi networks o e are homogeneous in nature. In the 1960s, the social psychologist Stanley Milgram wanted to know, for a given two persons A and B, were they linked to each other by a short chains of acquaintances. He determined the personal information about the target persons, and gave it to some individuals. Each starter individual had to choose a single acquaintance to send the letter 6

to, such that, the target can receive the letter in the shortest way, and the subsequent recipients had to follow the same procedure, until the letter arrived its target. From the completed chains, he found that the median number from the source to the target was six. Then he conducted what is known six degrees of seperation, it formulated as Any one of us is only about six acquaintances away from anyone else[2]. As many complex real-life networks are neither completely regular nor completely random, Watts and Strogatz (1998) introduced the concept of small-world networks[33]. They described the transition from the regular lattice, to the random graph, by rewiring the edges of a regular graph with probability p. The small-world networks as the random networks, have the property that, the connectivity distribution of a network peaks at an average value and decays exponentially[31]. Some complex networks display the so-called small-world (SW) eect: they are highly clustered, but the average length between any two randomly chosen nodes in the graph is short, a characteristic feature of random graphs. In 1998, the physicist Albert-Lzl Barabsi[3], with some of his colleagues at the a o a university of Notre Dame, mapped the connections of the Web, and the surprising result for them was that, the structure of the Web does not obey the the Erds-Rnyi random o e model of connectivity. A small number of the nodes have a high connectivity with the other nodes, while most of the nodes have a small number of connections. They named their network, the scale-free network. Recent studies have revealed that, the interaction networks displayed by most complex systems are heterogeneous. Most nodes are connected to a few ones, and a small number are linked to many other nodes. These distributions are thus very dierent from the Poissonian shape expected from a simple (Erds-Rnyi) random graph. Dierent types o e of networks are observed: from exponential to scale-free (SF), indicating dierent basic types of organisation[13]. The consequences of the small-world and scale-free patterns can be of great importance in recognise evolutionary paths, the origins of homeostatic stability and the sensibility to perturbations in biological networks. 7

The topology of a network can be characterised by three important properties, that are the characteristic path length, the clustering coecient and the degree distribution. An important property that is related to the degree distribution, the network resilience to the removal of its nodes.[23] What can happen to the topology of a network when a randomly fraction p of its nodes and their connections are removed? In the scale-free networks, the removal of a fraction p of its nodes, will break it down into a smaller disconnected parts, when p exceeds a critical value pc called the threshold. Bellow the threshold the network remains connected, but the lengths between the paths between the nodes will increase.[6] Networks vary in their level of resilience against the removal of nodes.[23] In [23], Newman explained the importance of the network resilience in epidemiology, where the removal of vertices in a contact network might correspond for example to vaccination of individuals against a disease. Because vaccination of individuals prevents them from catching the disease, and in addition to that, it may also destroy paths between other individuals by which the disease may spread.

1.3

Dynamics on Complex Systems

Complex networks are sets of many interacting components whose elaborate collective behaviour cannot be directly predicted and characterised in terms of the behaviour of their individual components. When the interactions between single components are suitably modelled, components can describe many dierent real-world units such as 2 providers. The unifying feature of the complex networks , is that, their global structure and dynamic evolution are the result of locally interacting agents distributed in the network[5]. Dynamical systems can often be modelled by dierential equations
dx dt

= v(x), where

x(t) = (x1 (t), x2 (t), . . . , xn (t)) is a vector of state variables, t is time, and v(x) = 8

(v1 (x), v2 (x), . . . , vn (x)) is a vector of functions that encode the dynamics. These dierential equations are oftenly nonlinear. Such nonlinear equations are typically impossible to solve analytically, but one can gain qualitative insight by imagining an abstract n-dimensional state space with axes x1 , x2 , . . . , xn . As the system evolves, x(t) ows through state space, guided by the velocity eld
dx dt

= v(x) like a speck carried along in a steady, viscous uid.

Suppose x(t) eventually comes to rest at some point x . Then the velocity must be zero there, so we call x a xed point. If we are modelling a physical system, then x is corresponds to an equilibrium state of the physical system being modelled. If all disturbances away from x damp out, x is called a stable xed point, it acts as an attractor for states in its vicinity. Another long-term possibility is that, x(t) ows towards a closed loop and eventually circulates around it forever. Such a loop is called a limit cycle. It represents a selfsustained oscillation of the physical system. A third possibility is that x(t) might settle onto a strange attractor, a set of states on which it wanders forever, never stopping or repeating.Such erratic, aperiodic motion is considered chaotic if two nearby states ow away from each other exponentially fast. Long-term prediction is impossible in a real chaotic system because of this exponential amplication of small uncertainties or measurement errors.[25]

Networks have a number of possible complications: 1. Structural complexity: the wiring diagram could be an intricate tangle. 2. Network evolution: the wiring diagram could change over time. On the WorldWide Web, pages and links are created and lost every minute. 3. Connection diversity: the links between nodes could have dierent weights, directions and signs. Synapses in the nervous system can be strong or weak, inhibitory or excitatory. 9

4. Dynamical complexity: the nodes could be nonlinear dynamical systems. In a gene network or a Josephson junction array, the state of each node can vary in time in complicated ways. 5. Node diversity: there could be many dierent kinds of nodes. The biochemical network that controls cell division in mammals consists of a bewildering variety of substrates and enzymes. 6. Meta-levels: the various levels can inuence each other. For example, network evolution, aects its topology.

1.4

Synchronisation in Networks of Complex Systems

A particularly interesting form of dynamical behaviour occurs in networks of coupled systems or oscillators when all the subsystems behave in the same fashion, that is, they all do the same thing at the same time. Such behaviour of a network simulates a continuous system that has a uniform movement, models neurons that synchronise, and coupled synchronised lasers and electronic circuit systems. Networks synchronisation has many applications in various elds, such as the synchronous information exchange in the Internet and the WWW, and the synchronous transfer of digital or analog signals in the communication networks. Many real-world problems have closed relationship with network synchronization, such as the spread of epidemic or computer virus. Each complex systems can be described as one of three important types: Synchronous complex systems: synchronous systems consist of more or less identical members which evolve synchronously with identical time evolution algorithms. A synchronous complex systems: contain disparate members which evolve dynamically in time with changing interconnect and usually dierent evolution algorithms for each member. 10

 Loosely complex systems are intermediate case between asynchronous and synchronous complex systems. They are synchronise every now and then; typically at the end of an iteration or time step in a solution. To predict the behaviour of a network of coupled dynamical systems, Strogatz assumed that[25], for the network of dynamical systems, each node would exhibit if it were isolated, then he asked the question what can be said about the collective behaviour if many such systems are coupled together?. He proposed to answer this question, that: If each node in the dynamical system has stable xed point and no other attractors, then the network tends to lock in static pattern. If each node has a chaotic attractor, then it can synchronise. But in a wide range of network topologies, synchronised chaos requires that the coupling be neither too week nor too strong. Otherwise spatial instabilities are triggered.

If each node has a stable limit cycle, and the oscillators are identical and coupled by smooth interactions akin to diusion, then these oscillators will oftenly synchronise, or form patterns depending on the symmetry of the underlying network. For the fully connected networks the completely synchronise state become likely.

11

Chapter 2 Structures of Complex Networks

2.1

Denitions and Preliminaries

As mentioned before, the three key measures of a network are the characteristic path length, the clustering coecient and the degree distribution. The characteristic path length L is simply dened as the average distance between any two nodes, or more precisely, the average length of the shortest path connecting each pair of nodes. If all edges are unweighted and undirected, then the distance between two nodes is simply the minimal number of edges, that must be traversed to get from one node to the other. The distance between the two nodes vi and vj is denoted by Dij . Mathematically, the characteristic path length denoted by L is dened to be:
N

L=
i=1

Di N

where Di is the distance between any pair of vertices. L generally measures the global properties of a graph and is independent of local structure. 12

The diameter of the graph G denoted by Diam(G) is dened to be: Diam(G) = maxi,j Dij The neighbourhood v of a vertex v is dened to be the set: v = {x : D(v, x) = 1, v = x} The set v is termed as the nearest neighbour of the vertex v. And generally, the k th nearest neighbour of a vertex v, denoted by v is dened to be the set: (k) = {x : D(v, x) k, v = x} v The second characteristic feature of real-world networks has been highlighted by Watts and Strogatz[33], who pointed out that most networks are highly clustered. One can dene a clustering coecient for a single node vi , denoted by Ci as Ci = 2Ei ki (ki 1)
(k)

where Ei is the number of all edges that actually exist among all rst neighbour of selected the node. If all the nodes are connected, then there would be ki (ki 1) edges among them. The clustering coecient overall the network is the average of all individual Ci s, i.e 1 N
N

C=

Ci
i=1

The clustering coecient C is a measure of how clustered, or locally structured, a graph is. In some networks, the most important characteristic of a single node, is its degree distribution[30]. The larger the degree of a node, the more important of it. If ki denotes the degree of the node i then, ki denotes the average degree of the

13

node in the network. The spread of node degrees over a network is characterised by a distribution function P(k), which gives the probability that, a randomly selected node has exactly k nearest neighbours. Generally the networks are divided into two general types: regular networks and random networks. If p is the probability that vi and vj are connected randomly, then in regular networks, p = 0, while in random networks 0 < p 1, and if p = 1, then the network is said to be completely random.

2.2

Random Networks
N (N 1) 2

Random networks were rst studied by P. Erds and E. Ryni. They dened random o e graphs as N nodes, connected with n edges, which are chosen randomly from possible edges[5]. In total there are precisely Cn n edges. An alternative denition is the binomial model[24]: we start with N nodes, and connect each pair of the nodes with probability p. Consequently, the total number of edges is a random variable with expectation value E(n) = p N (N 1) .If G is a graph with N nodes 2 and n edges, the probability of obtaining it by this graph construction process is binomial: P (G) = pn (1 p)
N(N1) n 2 N(N1) 2

dierent graphs with N nodes and

The construction of a graph is often called the evolution process. Starting with a set of N isolated vertices, the graph develops by the successive addition of random edges. The graphs obtained at dierent stages of this process correspond to larger and larger connection probabilities p, eventually obtaining a fully connected graph p 1 n =
N (N 1) .[12] 2

14

Erds-Rnyi Model(ER): o e Input: (N, p) where N is the number of vertices, and p (0 p 1)is the edge probability. Algorithm: Start with N isolated nodes. connect each pair of nodes with the same probability p.
11 00 11 00 11 00 11 00 11 00 1 0 1 0

11 00 11 00 11 00 11 00 11 00 1 0 1 0 1 0 11 00 11 00 11 00 11 00 11 00

11 00 11 00 11 00 11 00 1 0 1 0 1 0 11 00 11 00 11 00 1 0 1 0

1 0 1 0

11 00 11 00 11 00

11 00 11 00

Figure 2.1: Random Network.

Random networks are poorly clustered but have short path lengths. This is because the randomness makes it less likely that nearby nodes will have lots of connections, but introduces more links that connect one part of the network to another. Watts and Strogatz [18] showed that, the random graph, has a clustering coecient C
k N ln(N ) , ln(k)

<< 1, and a path length L

where k is the number of edges per vertex.

Hence, the random graph with p = 1, is poorly clustered, small-world, where L grows only logarithmically with N.

The degree distribution of a random network is Poissonian, P (k) = e<k> k k!

15

with a peak at P (< k >).

4 Poisson distribution 3.5

2.5

p(x)

1.5

0.5

0 0 1 2 3 4 x 5 6 7 8 9

Figure 2.2: Poisson distribution, with mean = 2

2.3

Regular Networks

A regular network is dened as a graph, where each node has exactly the same number of links to its neighbouring nodes. In regular networks the nearby nodes have large numbers of interconnections, but distant nodes have few. Examples of regular networks are a regular grids where all nodes have exactly four links, and hexagonal lattices, where each node is connected to three other nodes.

Regular networks have long path lengths, i.e., to go from one distant node to another one must pass through many intermediate nodes, but are highly clustered, i.e., there is a high density of connections between nearby nodes. A famous example of a highly clustered regular graph is the fully-connected graph (gure 2.3) in which every vertex is connected directly to all others. It is used in physics as the basis for mean-eld theory, as well as for some simplied models of physical systems such as the Sherrington-Kirkpatrick spin-glass model[22].

Watts and Strogatz [33] showed that, the regular graph, has a clustering coecients 16

11 00 11 00 11 00 11 00 11 00 1 0 1 0 11 00 11 00 11 00 11 00 11 00

11 00 11 00 11 00

11 00 11 00

1 0 1 0 1 11 0 00 11 00 11 00 11 00 11 00 11 00 1 0 1 0 11 00 11 00 11 00 11 00 11 00 1 0 1 0 1 0

1 0 1 0 1 0

11 00 11 00

Figure 2.3: example of a regular network

11 00 11 00 11 00 11 00 11 00 1 0 1 0 1 0 11 00 11 00 1 0 1 0 1 0

11 00 11 00

11 00 11 00

11 00 11 00 11 00

11 00 11 00 11 00 11 00 11 00 1 0 1 0 1 0 11 00 11 00

11 00 11 00 11 00

1 0 1 0 1 0 1 0 1 0 1 0 1 0

Figure 2.4: fully connected graph.

C 3 , and a path length L 4 with N.

N 2k

>> 1, where k is the number of edges per vertex. Then

the regular lattice is a highly clustered, large world where the length L grows linearly

For fully-connected graphs, the clustering coecient C is equal to 1, its maximum value. The degree distribution for the regular lattices, is obviously the uniform distribution.

17

2.4

Small-World Networks

Watts and Strogatz [33] studied what happens between the two extremes, p = 0 and p = 1, for the ER random graphs. They started with regular networks and rewired the nodes. That is, they decided whether to leave each edge connecting a pair of nodes in place, or to change it to connect the starting node to a dierent ending one, chosen at random. This decision was made at random, with probability p for each edge. Thus, if p = 0, the original regular network is unchanged, but if p = 1, the resulting network is completely random. Their computer experiments indicated that introducing a relatively small number of random connections, dramatically changed the character of the graph. That is, for small values of p, the graphs retained their properties of being highly clustered, but the average path lengths dropped dramatically. For example, for p = .01, the clustering coecient is over 95% of what it would be for a regular graph, but the characteristic path length is less than 20% of what it would be for a regular graph. They called these new graphs small-world networks.
1 0 1 0 1 0 1 0 1 0 1 0 1 0 11 00 11 00 1 0 1 0 11 00 11 00 11 00 11 00 11 00 11 00 11 00 11 00 11 00 1 0 1 0 1 0 1 0 1 0 1 0 1 0 1 0 1 0 1 0 11 00 11 00 11 00 11 00 11 00 11 00 11 00 11 00

Figure 2.5: Small-World Network.

The interesting part in their result is that small-world networks seem to be good models for a wide variety of physical situations. They showed that the power grid for the western U.S., the neural network of a nematode worm, and the Internet Movie Database all have the characteristics -high clustering coecient but short path length- of small18

world networks.

Watts-Strogatz Model: Input: (N, k, p) where N is the number of vertices, k is the distance in which each vertex can be connected to its neighbours by undirected edges, and p (0 < p 1) is the probability of rewiring each edge. Algorithm: Start with a ring lattice, with N nodes, each connected to the k th nearest neighbours. Replace original edges by random ones by probability p. Intuitively, one can see why small-world networks might provide a good model for a number of situations. For example, people tend to form tight clusters of friends and colleagues (a regular network), but then one person might move from his city to another city, introducing a random edge. The results of Watts and Strogatz then provide an explanation for the empirically observed phenomenon that, there often seem to be surprisingly short connections between unrelated people. The empirical results for most large networks show distribution that signicantly deviates from Poisson distribution. This degree distribution has a power law tail P (k) = k , and such networks are called scale-free, whereas (2 3), is called the scaling exponent. is important in dening the topology of a given network. Real-world networks are likely to be small-world networks. Some real-world networks display an exponential tail, but, despite of that, the functional form of P (k) still deviates from the Poisson distribution expected for a random 19

graph[24]. The degree distribution for the small-world network, in the original Strogatz-WattsNewman model [2], with k = 1 is given by: Dq = (1 p)Pq (p) + pPq1 (p) where Pq () = is the Poisson distribution. There is a more interesting phenomena which occurs if the graph is sparse (if the number of links in a graph is small compared to the total number of possible links). Look at the following graph: e q q!

Figure 2.6: Caveman graph with 33 nodes and 105 edges

It is called the Caveman graph. In the Caveman graph each set of nodes is in a small interconnected cave or cluster, and some nodes in each cluster are connected to few nodes of other clusters. This type of graph has a large clustering coecient and a short path length, while it is still being sparse.[28] If k represent the average number of connections a node has. As before, N represents the total number of nodes. Thus, the total number of connections in the graph is The caveman graph is sparse in the sense that k is much smaller than N. The graph consists of
N k+1 kN . 2

clusters. Within each cluster, each node knows every other

node. Thus, the clustering coecient is within a small fraction of the maximum possible clustering coecient of a connected sparse graph, and very close to 1. 20

The characteristic path length of a connected caveman graph is of the order of Hence, as N gets large and the graph remains sparse, L grows steadily.

N . k

The caveman graph thus represents one type of extreme graph large clustering coecient and large characteristic path length. It is small-world graph. Properties of Small-World Networks:[12] Sparseness: In a small-world network, the graph with N nodes has edges closer to O(N) than O(N 2 ). Compared with a complete fully-connected graph with the same number of nodes, the small-world graph is sparse. Small diameter: The diameters in small-world graphs increase logarithmically with the number of nodes. D log(N). Clustering: The small-world graph has a much higher clustering coecient than in a random graph. Threshold of the giant cluster appearance. |E| > Scale-free power-law degree distribution.
N . 2

2.5

Scale-Free Networks

Scale-free networks, are characterised by an uneven distribution of connectedness. Instead of the nodes of these networks having a homogeneous distribution, some few nodes act as very connected hubs.

Albert-Barabasi Model: Input: (n0 , m, t) where n0 is the initial number of vertices, m (m n0 ) is the no. of added edges, every time one new vertex is added to the graph, and t is the no. of repetitions. Algorithm: 21

Figure 2.7: Scale-Free Network, the red nodes (hubs) are highly connected with the other nodes in the network.

Start with n0 nodes. Every time we add one new node v, m edges will be linked to the existing nodes from v. Each existing node has a dierent probability p(ki ), p(ki ) = receive the connection from v. Scale-free networks have been used to explain behaviours as diverse as those of power grids, stock market, cancerous cells and the dispersal of sexually transmitted diseases. Put simply, the nodes of a scale-free network arent randomly or evenly connected. Scale-free networks include many very connected nodes, hubs of connectivity that shape the way the network operates. The ratio of very connected nodes to the number of nodes in the rest of the network remains constant as the network changes in size. In contrast, random connectivity distributions (the kinds of models used to study networks like the Internet before Barabsi and his team made their observation), predicted a that there would be no well-connected nodes, or that there would be so few, that, they would be statistically insignicant. Although not all nodes in that kind of network would be connected to the same degree, most would have a number of connections hovering around a small, average value. Also, as a randomly distributed network grows, the relative number of very connected nodes decreases[18]. 22
Pki , j kj

to

There are two dierent kinds of scale-free networks, i.e. networks with power law P(k), are considered: scale-free networks with no local clustering produced by the Barabasi-Albert model and scale-free networks with high clustering properties as in the model by Klemm and Eguiluz(2002), and their properties are compared to the properties of random graphs (exponential graphs).

As we stated before, the scale-free networks are heterogeneous in nature; that is, most nodes have few connections, and only a small number of nodes have many connections. The heterogeneity feature makes a scale-free network error tolerant, but vulnerable to attacks. i.e. the connectivity of such networks is highly robust against random failures, but it is also extremely fragile to attacks. The Internet chugs right along despite frequent router failures. On the other hand: the average performance of the Internet would be cut in half, if 1% of the most highly connected routers were incapacitated. The Internet will even lose its integrity with 4% of its most important routers being destroyed. This is known as the Achilles heel of the Internet. A power-law distribution shows that, most vertices have the same low degree, but a small number of vertices have a much higher degree. We have two limit cases for the Barabasi-Albert model[21]: No preferential attachment: Start with n0 nodes, at each time step add a new node, with m( n0 ) edges. (ki ) = No growth: 23
1 n0 +t1

P (k) =

k e m e m

1 Power-law distribution 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 1 1.5 2 2.5 3 x 3.5 4 4.5 5

Figure 2.8: The power-law distribution

Start with N nodes, and no edges, at each time step, a node is selected randomly, and connected with probability (ki ) =
Pki j kj

P (k) is not stationary, after T N 2 time steps, all nodes are connected. The shape of the degree distribution changes from an initial power-law to a Gaussian one.

2.6

Similarities and Contrasts

1. Average path length: Regular networks: L(0)

N 2k

>> 1. (long paths).

Small-world networks: L(p) is closed to L(1). (short paths). Random networks: L(1) Scale-free networks: L 2. Clustering coecient: Regular networks: C(0) 3 . (highly clustered). 4 Small-world: C(p) >> C(1). (highly clustered for small values of p, the clustering drops with increasing p). 24
lnN . lnk

(short paths). (short paths).

lnN . lnlnN

 Random: C(1)

k . N

(poorly clustered).

Scale-free: C N 0.75 , (highly clustered, 5 times larger than that, of a random graph), C decreases with the network size. 3. Degree distribution: Regular networks: Uniform distribution. Small-world networks: Dq = (1 p)Pq (p) + pPq1 (p) with Pq () = Random networks: Poisson distribution P (k) =
e<k> k . k! e q . q!

Scale-free networks: Power-low distribution P (k) Ck , 2 < 3.

25

Chapter 3 Dynamics and Synchrony

3.1 Denitions and Basic Concepts

Next, we will answer the following two important questions: When can the complex network achieve the synchronous behaviour? When is such synchronous behaviour stable, especially in regard to coupling strengths in the network? The general complex dynamical model, consists of N identical linearly and diusively coupled nodes, with each node being an n-dimensional dynamical system. This dynamical network is described by:
N

xi = f (xi ) +
j=1 j=i

A(t)cij (xj xi ); i = 1, 2, . . . , N

(3.1)

where xi = (xi1 , xi2 , . . . , xin ) Rn is a state vector representing the state variables of the node i, C(t) = (cij )nn , is the coupling link matrix between node i and node j (i = j), for all 1 i, j N at time t, A(t) = (aij (t)) RN N , is the coupling conguration matrix, representing the coupling strength and topological structure at time t, in which 26

aij is dened as follows: if there is a connection between node i and node j, then aij = 0, otherwise aij = 0, and the diagonal elements aii are dened by: aii =
j=1 j=i

aij = ki ;

i = 1, 2, . . . , N

(3.2)

Now the equation 3.1 can be written as:

N

xi = f (xi ) +
j=1

A(t)cij xj ; i = 1, 2, . . . , N

(3.3)

As a special case, the coupling link matrix C(t) can be a constant 0 1 matrix in the form = diag{r1 , r2 , . . . , rn } and the coupling conguration matrix A(t) = c(aij )N N for all time t, where c is a constant, and aij satises the condition that: if there is a connection between the node i and the node j (j = i), then aij = aji = 1 otherwise aij = aji = 0. Now the model (3.3) reduces to:
N

xi = f (xi ) + c
j=1 j=i

aij xj ; i = 1, 2, . . . , N

(3.4)

c is called the coupling strength of the network, and we obtain a Wang-Chen model[8]. In the Wang-Chen model, the state equations of the entire network is dened by:
N

xi1 = f1 (xi ) + c
j=1

aij xj1

xi2 = f2 (xi ) . . . xin = fn (xi ) 27

(3.5)

where the functions fi satisfy fi (0) = 0. The coupled network (3.4) is said to achieve asymptotically synchronisation, if: x1 (t) = x2 (t) = . . . = xN (t) = s(t), t (3.6)

where s(t) can be an equilibrium point, a periodic orbit, and even a chaotic orbit. Our assumptions about the coupling matrix A imply that, one eigenvalue of A is zero, with multiplicity one, and all the other eigenvalues of A are strictly negative. if 1 is the largest nonzero eigenvalue of the coupling matrix A of the network, the synchronisation state of network (3.4) is asymptotically stable[17], if: 1 T c (3.7)

where c > 0 is the network coupling strength, and T > 0 is a positive constant such that, zero is exponentially stable point of the n-dimensional system: z1 = f1 (z) T z1 z2 = f2 (z) . . . zn = fn (z) The stability of the synchronisation of the network can be characterised by the nonzero eigenvalues of the coupling matrix A; the network will synchronise if the eigenvalue 1 is negative enough.i.e. 1 is less than T . c

(3.8)

3.2

Synchronisation in Regular Networks

Two coupling congurations were studied in [17]: the easiest-to-implement nearest neighbour coupling: consists of cells arranged in a 28

ring and coupled to the nearest neighbours. The corresponding coupling matrix is: 2 1 2 1 1 (3.9)

1 1

1 2

the most dicult-to-implement global coupling: any two dierent cells are connected directly. The corresponding coupling matrix is: N + 1 1 1 . . . 1 1 N + 1 1 . . . 1 1 1 N + 1 . . . 1 ... ... .. 1 1 1 . . . (3.10)

. . . N + 1

for any given coupling strength, if the number of cells is large enough, the globally coupled network will eventually synchronise, while the nearest neighbour coupled network can not achieve such synchronisation under the same condition. We have the following question: for a nearest-neighbour coupled network, with a suciently large number of cells and with an arbitrary coupling strength, is it possible to achieve synchronisation of the network, by a small modication of the nearest-neighbour coupling conguration? The condition 3.7 means that, the entire network will synchronise provided that 1 is negative enough. In the case of nearest-neighbour coupling, the eigenvalues of the coupling matrix A are {4sin2 k N , k = 0, 1, . . . , N 1} 29 (3.11)

Therefore the nearest neighbour coupled network will asymptotically synchronise if 4sin2 k N T c

In the case of global coupled conguration, the coupling matrix A has zero as a single eigenvalue, and all the other eigenvalues are N, and therefore the network will asymptotically synchronise if n T c

3.3

Synchronisation in Small-World Networks

Wang and Chen [17], considered a one dimensional lattice of N vertices arranged in a ring with connections between only nearest neighbours. Each connection must be rewired with some probability p, where 0 < p < 1, hence restructuring the coupling matrix A. If aij = 0, aij is set to be equal to aji = 1 with probability p, then the diagonal elements aii must be re-computed. Now the coupling matrix A is a function in p and N, and so are its eigenvalues. Let pN to be the largest nonzero eigenvalue for the coupling matrix A, then, if pN T c

the corresponding network with small-world connections will synchronise. Wang and Chen found that: 1. For any given value of N, pN decreases to N as p increases from 0 to 1. 2. For any given value of p (0, 1), pN decreases to as N increases to +. and then, for any given coupling strength c > 0: 1. For any given N >
T , c

there exists a critical value p so that, if p p 1,

then the small-world will synchronise.

30

 2. For any given p (0, 1), there exists a critical value N so that, if N N, then the small-world connected network will synchronise.

3.4
3.4.1

Synchronisation in Scale-Free Networks

Stability Analysis

Wang and Chen[16] assumed that, the network is connected in the sense that, there are no isolate clusters. Then the coupling conguration matrix A = (aij ) RN N is symmetric, irreducible matrix. The ith row a(i, :) and the ith column a(:, i) of matrix A will be called ith the row-column pair of A. Equation (3.2) implies:
N

a(i, :)

= a(:, i)

=
j=1

aji = 2ki

(3.12)

The power law connectivity distribution makes a scale-free network extremely nonhomogeneous: the majority of nodes are small nodes with very small degrees, while a few nodes are big with very high degrees (rich get richer phenomena). That implies, most row-column pairs of the coupling matrix have a small 1 norm, and a few row-column pairs have a large 1 norm. Let 0 = 1 > 2 3 . . . N be the eigenvalues of A. If the N 1 of n-dimensional linear time-varying systems w = (Df (s(t)) + ck )w; k = 2, 3, . . . , N (3.13)

where Df (s(t)) is the Jacobian matrix, of the function f , evaluated at s(t), are exponentially stable, then the synchronised states (3.6) are exponentially stable. If s(t) is an equilibrium point, then a necessary and sucient condition for the synchronisation stability, is that, the real parts of the eigenvalues of the matrix Df (s(t)) + ck are all negative. 31

Given the dynamics of an isolate node and the inner linking structure , the synchronizability of network (3.4) with respect to a specic coupling conguration A; is said to be strong, if the network can synchronise with small coupling strength c.

In their construction of scale-free network, Wang and Chen [16 ]set n0 = m = m, and denoted by A(m, N) the coupling matrix of the scale-free dynamical network (3.4), which has N nodes and m(N m) connections. If (m, N) is the average value of the

second eigenvalue of A(m, N); then for a xed value of m, (m, N) is a decreasing and bounded function of N, satisfying: lim (m, N) = (m) < 0 (3.14)

which means that, (m, N) decreases to a negative constant (m) as N increases to in nity.

Wang and Chen [16] found that, for m = 3, 5, 7, 9, and 11, (m) 0.944, 0.973, 0.981, 0.9 and 0.985 respectively. And they concluded that, adding of new nodes in a scale-free network cannot decrease the synchronizability of the network. That is due to the selforganisation process of scale-free networks with a large size, which makes the synchronizability remain almost unchanged, despite constantly adding of new nodes.

3.4.2

Robustness and Fragility of Synchronisation:

To check the robustness of synchronisation in a scale-free dynamical network, Wang and Chen[16], considered the robustness against either the randomly or specical removal of a small fraction f , (0 < f << 1) of nodes in the network, which will change the coupling matrix. They argued that, if the second largest eigenvalue of the coupling matrix remains unchanged, then the synchronisation stability of the network will also remain unchanged after the removal of some of its nodes. 32

 Let A RN N and A = RN [f N ]N [f N ] be the coupling matrices of the original with N nodes and and the new network after removal [f N] nodes respectively; and 2 and 2 be the average values of the second largest eigenvalues of A and A respectively. If the nodes i1 , i2 , . . . , i[f N ] are the nodes removed from the network, then against each node ik both of the ith row and column must be removed from the original coupling k matrix A, and at the end, a matrix B can be obtained. The matrix A can be obtained by recomputing the diagonal elements of the matrix B; i.e. aij = bij
N

aii =
j=1 j=i

aij

Robustness of Syncronizability Against Failure: Wang and Chen [16], showed that, in the simulation, described by N = 3000, and m0 = m = 3, it was found that, even when as many as 5% of randomly chosen nodes are removed, the second largest eigenvalue of the coupling matrix remains almost unchanged. i. e. 2 = 2 which implies that, the syncronizability of the network is almost unaected. They mentioned that, the error tolerance of the syncronizability in scale-free networks may be due to their extremely inhomogeneous connectivity distributions. That is because of most of nodes are small nodes with very low degrees, then [f N] nodes will be selected with much higher probability if N >> 1 and f << 1. The removal of small nodes does not alter the path structure of the remaining nodes and thus does not destroy the connec tivity of the network. Hence, the matrix A remains to be an irreducible and symmetric matrix.Furthermore, a small node with a low degree corresponds to a row-column pair with a small 1-norm. So the second largest eigenvalue of the coupling matrix A remains 33 (3.15)

almost unchanged with the removal of such raw-column pairs with a small 1-norm.

Fragility of Synchronisation Against Attack: Wang and Chen [16], mentioned that, to simulate the inuence of an attack on the syncronizability of the network, one may rst remove the node with the highest degree, and then continue to remove the node with the next highest degree, then so nodes are removed in decreasing order of degrees. They found that, the magnitude of the second largest eigenvalue of the coupling matrix decreases rapidly almost decreases to half of its original value in magnitude, when only 1% of the most connected nodes was removed. At a low critical threshold, f 1.6%, 0, implying that, the whole network was broken into isolate clusters. The vulnerability of connectivity and synchronizability to attack in scale-free networks, is rooted in their heterogeneity distributions. That is, a small number of big nodes with high degrees, dominates the network dynamics, and the removal of a small percentage of them, implies that, the minor matrix B of A, is formed by removing a small percentage of row-column pairs of A, with big 1 norm.

34

Chapter 4 Application: Genetic Regulatory Networks

4.1 Background: Regulatory Networks
Each strand has a backbone formed of sugar molecules called 2-deoxyribose attached to a phosphate residue. The two strands are twisted together into a double helix, and linked together through molecules called bases. There are four bases for the DNA, adenene (A), thymine (T), cytosine (C) and guanene (G). The basic unit of the DNA consists of the sugar, the phosphate and its base and is called a nucleotide. In the DNA, the bases are paired such that, A is always paired to T and C is always paired to G. These two pairs are called pairs of complementary basis[10][16]. 2. RNA: RNA molecules are similar to the DNA molecules. The dierences between them are that: the sugar is ribose in RNA, instead of 2-deoxyribose, the base thymice (T) is replaced by the base Uracil (U), which also binds to the adenene, 35

1. DNA: The simplest structure of a DNA molecule has two chains called strands.

 the RNA is single stranded, and the DNA performs only one function that of encoding information, in the cell, while there are dierent types of RNA performing dierent functions, such as mRNA and tRNA[10]. 3. Proteins: a protein is a long chain of molecules called amino acids. There are twenty dierent amino acids can be observed in the nature. Proteins are produced in a structure of the cell called a ribosome. In the ribosome the amino acids are assembled one-by-one according to information encoded in the messenger RNA (mRNA). The long chains of amine acids then folding the appropriate proteins. Proteins are divided into two main groups; structural proteins which are the main building blocks of tissues; and enzymes, which catylize chemical reactions.

4. Genes: each protein or RNA found in an organism is encoded in the DNA. Each cell of an organism has a few very long DNA molecules called chromosomes, and certain contiguous stretches of a chromosome encode information for building proteins. Such a stretch of DNA that contains information for building a protein or RNA molecule is called a gene. The sequence of amino acids for a given protein is encoded by using triplets of nucleotides called codons to specify each amino acid contained in the protein. For example, the codon CCG encodes the amino acid glycine, AUG encodes methionine but also it encodes the beginning of a gene, while the codons TGA, TAA and TAG encode a stop signal. 5. The Central Dogma of Molecular Biology: In Eucaryotic cells, the DNA is found in the nucleus, while proteins are made in the cytoplasm. A messenger molecule is used to carry the information from the nucleus to the ribosomes in the cytoplasm. The beginning of a gene is recognised due to a promoter (DNA region serves 36

as an indication of a gene). The codon AUG signals the start of a gene. Having recognised the beginning of the gene by the mRNA polymerase, it is copied to the mRNA. This process is called the transcription. The mRNA travels out of the nucleus, into the cytoplasm, where it joins up with it. In the cytoplasm, are amino acids and transfer RNA (tRNA) molecules. Each tRNA molecules has three bases at one end, which represent only one amino acid. The corresponding amino acid, attaches to the other end of the tRNA. The tRNA which has three bases called anti-codons to t the rst three on the mRNA brings its amino acid to the ribosome. The next tRNA brings its amino acid, and the two amino acids are chemically joined together. The mRNA moves along by three bases and the rst tRNA is released, while a third tRNA arrives with its amino acid. The process continue until a whole chain of amino acids (protein) is made according to the code on the mRNA, which was originally copied from the DNA in the nucleolus. This process is called the translation[16].

Figure 4.1: Source of this gure [29]

37

6. Regulation of Gene: The DNA molecules found in chromosomes are millions to hundreds of millions of base pairs in length. To access a specic piece of information stored within a DNA molecule, it is rst necessary to nd the specic sequence that contains it. This process uses two components. First information stored in DNA must have a molecular address. This address both identies the informational sequence and contains instructions for determining when and where the information should be used or expressed. Generally this molecular address is itself a set of DNA sequences that are located near the target gene.These regulatory sequences are also known as cis-acting factors. Proteins are used to recognise these regulatory sequences. These proteins are known as transcription factors because they regulate transcription. They are sometimes called trans-acting factors, because they are products of other genes, while cis-acting factors are an essential part of the gene being regulated. Transcription factors fall into two broad groups: Positively-acting transcription factors, known as activators, stimulate transcription. Negatively-acting transcription factors, known as repressors, suppress transcription. Whether a transcription factor acts as a repressor or an activator may depend on the context in which it nds itself, and the other polypeptides with which it interacts.

7. Genetic Regulatory Networks: Indirectly we saw the three components of the cellular network; the genome in which genes can aect each others level of expression; the proteome, dened the set of proteins and their interactions by physical contact; and the metabolic network, integrated by all metabolites and the pathways which link each other. These sub-networks of the cellular network are very intertwined since for in38

stance, genes can only aect other genes through special proteins. Some metabolic pathways regulated by proteins themselves, may be the very ones to catalyse the formation of nucleotides, in turn aecting the process of translation[8]. A cell type depends on the particular subset of active genes, where the gene expression pattern needs to be stable but also adaptable. Genes regulate each others activity by coding for transcription factors, which may enhance or repress the expression of other genes by binding, at particular sites. A given gene may directly regulate just a small set of other genes, those genes regulate other genes in turn, so a gene may indirectly inuenced by many genes upstream. A gene may directly or indirectly contribute to regulating itself. The result is a genetic regulatory network (GRN), a complex feedback web of genes turning each other on and o.

4.2

Modelling Genetic Regulatory Networks

Mathematical models of GRN have been developed to allow predictions of the models to be tested. Regulatory networks may be irreducible, and the computer modelling of them, is the only way to deal with their complexity. Kauman adopted the complementary perspective of studying Boolean Networks wired in random. He aimed to nd properties which would apply to the system in its entirety.

4.2.1

Boolean Network Model

In Kauman model genes are connected by directed links(transcription factors), updating their on-o state in parallel, according to the combinatorial logic of their inputs. The systems dynamic can be described by[8]:
t+1 t t t gi = fi (gj1 , gj2, . . . , gjK )

(4.1)

39

The K inputs of each node are chosen at random, among the N units of the system and the functions are chosen such that, the output have 1 with probability p, and 0 with probability 1 p. The parameter K denes the average connectivity between nodes; and p actually tunes the susceptibiliy of the function to changes in the input value. K and p are the only two interesting parameters in this model. The model has been criticized for being too simple, that parallel synchronously updated with the evolution of the time using equation (4.1) from the values of their inputs. The global state S of the system, is given by the composite state of all the genes, that is, S = (g1 , g2 , . . . , gN ) S represents a point in the space of all possible states, and at each time step it jumps to a dierent point, following a trajectory given by the network conguration, starting at the chosen initial state. As time goes on, a state will be reached that has already been visited before, closing the trajectory into either a loop of a single state, if this state maps onto itself. The dierent subsets of the starting states that end in the same loop are called basins of attraction. In a cell types gene expression pattern over a span of time, a particular gene may, be either on, o, or changing. If a large proprtion of the genes are changing, chaotic dynamics, the cell will be unstable. Dynamics that settles to a pattern where a large proportion of the genes are permanently on or o (frozen) may be too inexible for adaptive behaviour. Cells constantly need to adapt their gene expression pattern in response to a variety of hormone and growth/dierentiation factors from nearby cells. A cell type may be a set of closely related gene expression patterns, on the attractors, or shifting around within the basin of attraction, allwoing an essential measure of exibility in behaviour. Too much exibility might allow a perturbation to ip the dynamics too readily into a dierent basin of attraction, to a dierent cell type.

40

The basins of attraction in random Boolean networks are idealized models for the stability of cell types against mutations, and also for their response to perturbation, the dynamics may jump to a dierent subtree in the same basin, which would temporarily adapt the pattern, or it may be ipped to another basin, a dierent cell type. In this case the basin of attraction eld remains unchanged. Alternatively, the network itself may undergo a mutation, resulting in an altered basin of atracion eld. This model provides a mechanism for both the stability and adaptability of gene expression[34].

4.2.2

Dierential Equations Models

This method models reaction kinetics of the production, diusion/transport and binding of proteins to genes, in order to make discoveries. This method assumes that, protein production is a continuous process. The cellular concentrations of proteins, mRNA, and other molecules at the time t, represented by continuous variable xi (t) R+ . Then, the regulatory interactions are modelled by the kinetic equations: xi = fi (x), 1in (4.2)

The rate of change of variable xi is a function of other concentration variables x = [x1 , x2 , . . . , xn ] . Now we can describe two types of feedback systems(they are not the only types of systems): Negative feedback systems. Positive feedback systems. 1. Negative Feedback Systems: In this system, gene encodes the protein inhibits its own expression. Then if x1 denotes the concentration of the mRNA, and x2 denotes the concentration of the protein, the model for the negative feedback systems is 41

given by the two equations: x1 = 1 x1 + 1 f (x2 ) x2 = 2 x1 + 2 (x2 ) where 1 , 2 > 0 are the production rate constants, and 1 , 2 > 0 are the degenerProtein Gene

(4.3)

__

mRNA

Protein

Figure 4.2: Negative feedback system ation rate constants. The function f (x) is given by: f (x) = the threshold value. This system has a single steady state at x = 0. The values of x1 and x2 are given by: x1 = 0 : x2 = 0 : 1 f (x2 ) 1 2 x1 = x2 2 x1 =
n , n +xn

where > 0 is

This steady state is stable, that is, after perturbation system will return to steady state (homeostasis).

2. Positive Feedback Systems: In this system, the gene encodes the protein activating its own expression. 42

1.2

0.8

x1

0.6

0.4

0.2

0 0 0.2 0.4 0.6 0.8 x2 1 1.2 1.4 1.6

Figure 4.3: The steady states are represented by the intersections between the two curves n 1 x1 = 1 f (x) = n n and the straight line x1 = 2 x2 +x 2 As before, x1 denotes the concentration of the mRNA, and x2 denotes the conProtein Gene

mRNA

Protein

Figure 4.4: Positive feedback system centration of the protein, and the model for the positive feedback systems is given by the two equations: x1 = 1 x1 + 1 f (x2 ) x2 = 2 x1 + 2 (x2 ) where 1 , 2 > 0 are the production rate constants, and 1 , 2 > 0 are the degeneration rate constants. But, the function f (x) this time is given by: f (x) = 43
xn , n +xn

(4.4)

where > 0 is the threshold value.

1.2

0.8

x1

0.6

0.4

0.2

0 0 0.2 0.4 0.6 0.8 x2 1 1.2 1.4 1.6

Figure 4.5: The steady states are represented by the intersections between the two curves n 1 x1 = 1 f (x) = nx n and the straight line x1 = 2 x2 +x 2

There are also other deterministic models as the time delay feedback system model.

4.2.3

The Articial Genomic Model

Using articial genomes to model genetic networks is a new method rst used by Torsten Reil[26]. The method uses a randomly generated string of digits to represent the genome. A TATA box type promoter is dened which in Reils model is 0101. The 6 digits preceding this sequence are considered to be a gene. When a gene is being transcribed the digits all increase by one so a gene sequence like this 012130 becomes 123241. The pattern produced is then matched to the rest of the genome. If a pattern matches a position in the genome the next 0101 sequence following from that pattern is found and is then switched on or o depending on the patterns sequence. Whether a pattern represents a repressor or derepressor depends on the patterns sequence. Four parameters can be modied in Reils implementation, that are; the genome size, gene length, base, and the degree of inhibition. Reil used this model and found that, it produced cycles, which were like that of cell 44

cycles. This system was able to show both stability and multi-periodicity, when the programme was started with just one gene switched on. Once the pattern is produced every gene, which has this as a promoter is switched on. More patterns are produced, and more genes are turned on and o, producing cycles which mimic cellular cycles. This system also shows a level of robustness as transient disturbances in the expression prole usually don not alter the expression pattern; but knocking out specic genes, does aect the expression prole. Manually switching on or o specic genes, could also cause movement of the cell into a dierent attractor cycle, like dierentiation. Many models based on Reils model, with some modications in it, were constructed to determine the dynamics in the regulatory networks, such as the model by Hallinan and Wiles[11], 2004. Their model was dierent from Reils model in two major ways, the rst was the manner in which inhibitory links are implemented, and the second, is their update scheme (They used synchrony parameter). Hallinan and Wiles obtained as results; transient graphs with low synchrony, and high synchrony.

45

Chapter 5 Discussions
The complexity of a network can occur from either its structure or the dynamics of its complex nodes, or probably both of them. The complex networks with dierent topologies (regular, small-world, completely random or scale-free structures), can be always characterised by the three characteristic properties; the characteristic path length, the clustering coecient and the node degree distribution. Random removing of a fraction of nodes with their connections from some network with a probability p, may cause in breaking down that network into disconnected smaller networks, if p exceeded a threshold value pc . So, networks vary in their resilience to the removal of some of their nodes. The scale-free networks are more robust than random networks against random node failures, but fragile to removing the highly connected nodes. The dynamics of the nodes in networks, may end by synchronous, asynchronous or a transient synchronisation behaviour, and most of large-scale scientic and engineering computations are synchronous or loosely synchronous. The system can achieve the synchronisation, if the second-largest eigenvalue of the coupled-conguration matrix is small enough. And the regular lattices can achieve the synchronisation faster than the random networks. To reveal results about the synchronisation in small-world networks, Wang and Chen 46

[32] started with a nearest-neighbour coupled dynamical network, then used the StrogatzWatt algorithm to construct a small-world network. They found that, for any given coupling strength and a suciently large number of cells, the small-world coupled continuous system can achieve the synchronisation, for small values of p. The synchronisation is chaotic. Wang and Chen [31] also showed that, the scale-free dynamical network is much easier to achieve synchronisation than the locally regularly coupled dynamical network, which explains why many real large networks exhibit atendancy towards synchronisation, and the root of this synchronisation is the scale-free nature of the network. They showed that, the synchronizability of a scale-free network is robust to the random removal of nodes, but fragile to the removal of nodes with high connections. For the genetic regulatory networks, many methods of modelling were created to describe the dynamics of these network. These methods, included the boolean networks, the dierential equations, the Bayesian methods and the articial genome models, where the choice of approach depend on the aim of the analysis, and the given information. All the above methods used to model the genetic regulatory networks depend on the computer in understanding the genetic regulatory processes. In the boolean networks model, the values of the variables are updated synchronously, and so in the dierential equations models. It is not the case in the real life, the genes are activated asynchronously. On the otherhand, many researches adopted the technique of the asynchronous updade for the variables of the given models, and revealed the exsistance of pseudo-periodic loose attractors[11]. Generally, the results obtained for the behaviour of the GRNs, ranging from stability to limit cycles to chaotic behaviour, depending on the connectivity and degree of inhibition of the network.

47

Bibliography
[1] Albert Rca, Albert-Lszl Barabsi, Topology of Evolving Networks: Local Events e a o a and Universality, Physical Review Letters, Vol. 85, No. 24, Dec. 2000. [2] Almaas E., Kulkarni R.V., Stroud D., Characterizing the Structure of Small-World Network, Physical Review Letters, March 2002. [3] Barabsi A., Bonabeau E., Scale-Free Networks, Scientic American, 288, P. 60-69, a 2003. [4] Cancho R. F. i , Sol R. V. , Optimization in Complex Networks, Santa Fi e Institute, http://www.santafe.edu/s/publications/, Nov. 2001. [5] Caldarelli G., Introduction to Complex Networks,

http://www.cosin.org/publications/caldagranada.pdf, 2002. [6] Cohen R., Eraz K., ben-Avraham D. and Havlin S., Resislience of the Internet to Random Breakdown, Physical Review Letters, 85, P. 4626-4628, 2000. [7] Crucitti P., Latora V., Marchiori M. and Rapisarda A., Eciency of Scale-Free Networks: Error and Attack Tolerence, http://arxiv.org/pdf/cond-mat/0205601, 2002. [8] Fernndez P. and Sole R. V., The Rule of Computation in Complex Regulatory a Networks, www.santafe.edu/s/publications/ Working-Papers/03-10-055.pdf, 2001. [9] Fox G. C., Roy D. Williams, Paul C. Messina, Parallel Computing Works, Morgan Kaufmann Publishers, ISBN 1-55860-253-4, Inc. 1994. 48

[10] Gonnet G., Cannarozzi G and von Rohr P., Lecrure Notes in Computational Biology, Week1 Basic Biology, http://www.wr.inf.ethz.ch/education/cb/, 2001. [11] Hallinan J. and Wiles J. (Accepted), Asynchronous Dynamics of an Articial Genentic Regulatory Network, Ninth International Conference on the Simulation and Synthesis of Living Systems (ALife9) Boston, Sep. 2004. [12] Hu M., Exploring the Topology of Small-World Networks,

www.cs.rit.edu/ mxh2906/project/le/defense.pdf , 2004. [13] Icrea complex system lab, Evolution of Complex Networks,

http://complex.upf.es/ ricard/complexnets.html, 2003. [14] Jiang B., Clarmunt, Topological Analysis of Urban Street Networks,

http://www.ecole-navale.fr/fr/irenav/cv/claramunt/EPB2003.pdf [15] Jinho L , Xinghuo Yu, Guanrong Chen, Chaos Syncronization of Complex Dynamu ical Networks, Physica, A 334, P. 281-302, 2004. [16] Jones M. and Jones G., Biology, Cambridge University Press, ISBN 0-521-45618-5, 9, 2002. [17] Kleinberg J. Small-World Phenomena and the Dynamics of Information, http://www.cs.biu.ac.il/ galk/teaching/P2P/kleinberg01smallworld.pdf [18] Li X., Wang X. and Chen G., Synchronizaion in Complex Dynamical Networks and its Applications, Conference on Growing Networks and Graphics in Statistical Physics, Finance, Biology and Social Systems, Roma, Sep. 2003. [19] Los Alamos National Laboratory, Complex System Modelling,

http://www.c3.lanl.gov/ rocha/complex/complexHP.html, 2004. [20] Louis M Picora, Thomas L. Carroll, Master Stability Functions for Synchronized Coupled Systems, Code 6343, Naval Research Laboratory, Washington, DC 20375, Jan 1998. 49

[21] M ckstein u

U.,

Statistical

Mechanics

of

Complex

Networks,

http:/www.tbi.univie.ac.at/ ulim/, Nov. 2002. [22] Newman M. E. J., The Structure and Function of Networks, Computer Physics Communication, 147, p. 40-45, 2002. [23] Newman M. E. J., The Structure and Function of Complex Networks, SIAM Review, 45, P. 167-256, 2003. [24] Porekar J. Random Networks, http : //www

f 1.ijs.si/ rudi/sola/RandomN etworks.pdf , 2002. [25] Strogatz S. H., Exploring Complex Networks, Nature, 410, P. 268-276, March 2001. [26] Reil T., Dynamics of Gene Expression in an Articial Genome Implications for Biological and Articial Ontogeny, Proceeding of the 5t h European comfeerence on Articial Life, P. 457-466, Springer Verlag, 1999. [27] Thain M. and Hickman M., The Penguine Dictionary of Biology, Penguine Group, ISBN 0-14-051359-0, 10, 2001. [28] Vertanen S., stochastic online clustering of massive graph,

http://www.research.ibm.com/nips03workshop/Posters/Virtanen.pdf. [29] Vierstraete A., The Central Dogma of Molecular Biology,

http://allserv.rug.ac.be/ avierstr/principles/centraldogma.html, 1999. [30] Wang X., Chen G., Complex Networks: Small-World, Scale-Free and Beyond, IEEE Circuits and Magazine, p. 6-20, 2003. [31] Wang X., Chen G., Syncronization in Scale-Free Dynamical Networks: Robustness and Fragility, IEEE Transactions on Circuits and Systems: Fundamental Theory and Applications, Vol. 49, Jan 2002. 50

[32] Wang X., G. Chen, Syncronization in Small-World Dynamical Networks, International Journal of Bifurcation and Chaos, Vol. 12, No. 1, P. 187-192, 2002. [33] Watts, Strogatz S. H., Collective Dynamics of Small-World Networks, Nature, 393, P. 440-442, June 1998. [34] Wuensche A., Basins of attraction in network dynamics: A conceptual framework for biomolecular networks, http://www.santafe.edu/ wuensch/.

51