Vision Mission of JIIT

Networks of Life and its Departments

Course Code: 16B1NBT531( Open Elective)

B Tech VII Semester

AY:2023-24 Programme
Educational
Objectives
Core Course (PEOs) of UG and
PG Programmes

Department of Biotechnology
JIIT NOIDA

Course Coordinator: Dr. Chakresh Jain

 Module 3:
Multilayered Graph, Percolation,
rewiring
Multilayer networks
• Multilayer networks provide
• an efficient tool for studying complex systems, and with current, dramatic
development of bioinformatics tools and accumulation of data, researchers have
applied network concepts to all aspects of research problems in the field of biology
• The nodes of the network are replicated over layers, and each layer
represents a particular aspect of connection between the nodes
• A multi-layer graph consists of multiple layers of weighted graphs, where
the multiple layers represent the different aspects of relationships.
• Considering multiple aspects (i.e., layers) together is essential to achieve a
comprehensive and consolidated view
• multilayered graphs can reveal patterns, trends, and insights in network
Multilayer networks
• A layer graph specifies the architecture of a deep learning network with a more
complex graph structure in which layers can have inputs from multiple layers and
outputs to multiple layers.
• Networks with this structure are called directed acyclic graph (DAG) networks.
• A multilayer network is a type of complex network that consists of multiple
layers, each representing a set of nodes and edges with specific relationships.
• These layers can interact with each other, providing a more comprehensive
representation of complex systems where different types of relationships coexist
• Mathematical Representation: Mathematically, a multilayer network can be
represented as a tensor, where each layer corresponds to a matrix.
• The entries of the matrix indicate the presence or absence of edges between
nodes in that layer.
Multilayer networks
• They are employed in the modelling of big networks, with
heterogeneous nodes (vertices) or relations (edges).
• Considering that this framework has many applications and in
different fields, its interpretation and implementation depend on the
subject that it’s serving.
• The main difference between these types is the criteria to link a node
to a layer.
• Multilayer networks are classified for two main
• Node-colored graphs (NCGs)
• dge-coloured graphs (ECGs)
Multilayer networks: Node-colored graphs

• Node-colored graphs are

representations of systems
with heterogeneous nodes.
• Nodes have different aspects
or types, defined by colors.
• In most of the cases, the
graph is layer-disjoint, i.e. the Node-colored Graphs. Nodes having similar colors are
node can only belong to one grouped in the same layer. The edges are the same as in
the original network
layer, having only one color
 Multilayer networks: Edge-colored graphs
• Edge-colored graphs are
representations of systems
with heterogeneous
connections between the
nodes.
• The graph GE is a tuple
defined by a set of nodes V,
a set of colors C with length
b, and a set of edges E,
each assigned a type or
aspect defined by the color.

The nodes of the original networks are replicated over the different layers. The layers represent the different aspects
of relationships in the network. Edges are divided among the layers based on their colors
layered graph
• These are used for visualizing and understanding the relationships and
dependencies within the graph
• The layered graph layout approach consists of three steps:
1. Layer assignment: the nodes are assigned to horizontal layers such that
the edges point downwards.
2. Crossing reduction: the algorithm computes a sequence of the nodes
within each layer, minimizing the number of crossings between edges.
3. Coordinate assignment: the nodes are assigned to coordinates
maintaining the layers and sequence calculated in the previous steps
layered graph : Algorithm
• Layered graph layouts are commonly used in the following application
areas: workflow visualization, call graph visualization, entity-relationship
diagrams, activity diagrams, biochemical/metabolic pathways, genealogical
data, and network management
• A layered graph drawing algorithm e.g.
1. Sugiyama Framework: This is a foundational framework for layered graph drawing
that introduces the concept of node layers and hierarchical graph layout.
2. Hierarchical Drawing Algorithms: Algorithms like the top-down and bottom-up
approaches are commonly used for hierarchical graphs, where nodes are organized
into levels.
• The primary goal of layered graph drawing is to improve the readability and
understanding of complex relationships within a graph.
• Apart from that it is also helpful in conveying the inherent hierarchical or
layered structure of the data, making it easier for users to interpret and
analyze
 Sugiyama Method
• The Sugiyama Method:
• Cycle Removal
– may temporarily Reverse some edges
– each cycle must have at least one edge against the flow
(NP Hard), requires heuristic (e.g. enhanced greedy
heuristic) or Randomized Algorithms.
• Layering. (assigning y)
– vertices may be introduced to split edges
• Node Ordering
– the Ordering is all that matters (not co-ordinates), NP
Hard.
– Many heuristics. e.g. Layer-by-layer sweep (two-layer
crossing problem), addressed by 1. Sorting, 2. Barrycentre,
or 3. Median, methods.
• Co-Ordinate Assignment.
Algorithm
• Layered graph drawing or hierarchical graph drawing is a type of graph
drawing in which the vertices of a directed graph are drawn in horizontal
rows or layers with the edges generally directed downwards
• The ideal form for a layered drawing would be an upward planar drawing,
in which all edges are oriented in a consistent direction and no pairs of
edges cross.
• However, graphs often contain cycles, minimizing the number of
inconsistently oriented edges is NP-hard, and minimizing the number of
crossings is also NP-hard;
• so, layered graph drawing systems typically apply a sequence
of heuristics that reduce these types of flaws in the drawing without
guaranteeing to find a drawing with the minimum number of flaws.
Implementations of the multilayer framework
1. Multiplex networks
• Multiplex Networks are edge-
colored graphs, where the
nodes connect with edges
belonging to M different
aspects .
• The edges are embedded based
on their type in different layers
all containing the complete set
of nodes X of length n
• . Multiplex networks explore
and incorporate the
interconnectivity of the same
system in multiple channels
represented by the layers

A Multiplex Graph. The nodes of the network are replicated over layers, and each layer
represents a particular aspect of connection between the nodes
Implementations of the multilayer framework
2. Multilevel networks
• Multilevel networks are
edge-colored graphs. They
are similar to multiplex net-
• works, with a difference
being that layers can
contain not only a subset of
edges but a
• subset of nodes as well.
The graph is a tuple defined
by the sets of nodes X,
• edges E, and layers S with
length p

Multilevel Graph. Each layer of the graph is a subset of the original network (nodes and
intra-edges). The inter-edges only connect the same nodes on different layers
 Implementations of the multilayer framework
3. Multi-Hypernetworks or
hypergraphs are node-based graphs
formed by different intersecting
communities or sub-networks.
• A Multi-hypergraph is defined by a
pair (X, H), X being the set of
nodes, and H a multi-set of subsets
of X being the edges
• Multi-Hypernetworks are not
layer-disjoint, but node-aligned
since one node can be assigned to
multiple layers, based on the
intersection of the subsets.
Hypernetwork. Adapted from . a The network in a monoplex
view; b The network in a multilayer view. Nodes belonging to
the same ensemble are assigned the same layer. All the nodes
on one layer are intra-connected. The same nodes on different
layers are interconnected (dotted edges)
Multilayered Graph modeling
Visualization of multilayered graph

• Visualization of multilayered graphs involves representing complex

relationships and interactions among entities using multiple layers of
interconnected nodes and edges.
• Python library, Py3plex, which focuses on the visualization and
analysis of multilayer networks.
• And other example includes visualizing multilayered graphs. Such as
Gephi, Cytoscape, and NetworkX in Python.
• The library implements a set of simple graphical primitives supporting
intra- as well as inter-layer visualization
Example of Multilayer network in biology
• PPI:
• The network could be seen as an edge-colored Multiplex or Multilevel network
inspecting diverse aspects of interactions.
• OhmNet is an algorithm that transforms monoplex networks into a multilayer model.
• This algorithm aims at studying proteins in different tissues and learning their
features.
• In this model, the tissues act as layers, and the proteins act as nodes
• Cell networks:
• Cell networks or pathways represent complex functions and reactions that occur in
the cell. They describe interactions between genes, proteins, and metabolites. The
study of these different substrates results in a heterogeneous network formed of
different types of nodes and interactions.
• usage of a multilayer framework helps to understand the behavior of cancer cells.

Ref: https://bdataanalytics.biomedcentral.com/articles/10.1186/s41044-020-00046-0
Multilayer Cancer Cells’ Network.
The Figure shows two graphs, normal and disease. The nodes in these graphs are the proteins, assigned to seven
layers reflecting seven cancer types
Example of Multilayer network in biology

• :Gene expression networks : The complexity in genetic networks lies

in the diversity of interactions between genes.
• A gene network is a collection of gene-gene regulatory connections.
• It contains information on genes affecting each other with their
expression levels.
• These networks can be inspected from a multiplex or a multilevel
framework, with layers representing co-expression profiles in
different settings including different time points, diseases, cells, or
organisms, as well as from a Hypernetwork framework, with edges
connecting more than two genes
Example of Multilayer network in biology

• Human neural networks:

• Neural networks are one of the most complex networks in the human
body.
• A brain network is a structural network where nodes represent neural
elements, i.e. the neurons or neuronal regions, and edges represent
the physical connection between them, i.e. synapses or axonal
projections.
• The connections in these networks are also affected by spatial factors,
which means that the location and distance between the elements
play a role in the probability of them being connected
Ref:
• https://bdataanalytics.biomedcentral.com/articles/10.1186/s41044-
020-00046-0
Percolation
• Percolation is the process of a liquid slowly passing through a filter
• Percolation actually describes a phase transition process of network
failure, whose critical point distinguishes the network from connected
to disconnected. Percolation theory makes use of statistical physics
principles and graph theory to analyze such change in the structure of
a complex network
• Percolation is a process that impairs network connectedness by
deactivating links or nodes.
• This process features a phase transition that resembles paradigmatic
critical transitions in epidemic spreading, biological networks, traffic
and transportation systems
Percolation of network
• In the context of networks, percolation involves the study of how the connectivity
of the network changes as nodes or edges are randomly removed.
• Percolation in the context of networks typically refers to the study of how a
substance or influence spreads through a network
• The percolation threshold is a critical point where the network transitions from
being mostly connected to mostly fragmented.
• This concept is relevant in various fields, including the study of epidemics,
network resilience, and phase transitions in physics.
• Percolation takes place if the neighbouring active cells (nodes) of a network,
having a certain probability, group together and form a cluster which becomes
gradually large enough to connect two sides of the net or two chosen nodes.
• It is useful to study the robustness and vulnerability of these networks.
Importance of Percolation
• Reliability of a network using percolation theory
• Network failure can be regarded as a percolation process and the
critical threshold of percolation can be used as network failure
criterion linked to the operational settings under control.
Percolation process
• The percolation process involves systematically removing nodes or edges
from the network and observing the impact on the overall connectivity.
• In the case of biological networks, percolation models can be applied to
study:
• Robustness of Biological Networks:
• Random Failures: Simulating the random loss of nodes (e.g., proteins or genes) in a
biological network and observing how the network's functionality changes.
• Edge Removal: Analyzing the impact of removing random interactions (edges)
between biological elements on the overall network connectivity.
• Vulnerability to Targeted Attacks:
• Node Removal: Investigating the effect of targeted removal of specific nodes (e.g.,
essential genes or proteins) on the overall network structure and function.
• Edge Removal: Examining the consequences of selectively eliminating crucial
interactions (edges) in the network.
Percolation process
• Identification of Critical Nodes or Edges:
• Percolation Threshold: Determining the critical point at which a significant portion of
the network becomes non-functional, providing insights into the network's
resilience.
• Identification of Hubs: Identifying nodes that, when removed, have a
disproportionate impact on the network's connectivity.
• Disease Spread and Intervention Strategies:
• Disease Propagation: Modeling the spread of diseases or perturbations through the
network and assessing how interventions at specific nodes or edges can mitigate the
impact.
• Evolutionary Dynamics:
• Adaptive Changes: Investigating how the network adapts to changes over time by
considering the addition or removal of nodes and edges.
Key features of Percolation
• Robustness and Vulnerability: Percolation studies help identify the critical components
in a biological network. Removal of nodes or edges can simulate various perturbations,
such as mutations, environmental changes, or targeted interventions. Understanding
which nodes or edges are critical for maintaining network connectivity is essential for
assessing the robustness or vulnerability of the biological system.
• Critical Threshold: Percolation theory often involves the concept of a critical threshold.
This is the point at which a small change, such as the removal of a single node or edge,
can lead to a significant change in the connectivity of the network. The critical threshold
is associated with phase transitions in the network structure.
• Emergence of Giant Components: As nodes or edges are removed from the network, the
size of the largest connected component may change. In percolation studies, researchers
often focus on the emergence of giant connected components, which are large clusters
of nodes that remain connected even after a significant fraction of the network is
removed.
Key Features of Percolation
• Network Resilience: Percolation studies provide insights into the
resilience of biological networks. Resilient networks can withstand
perturbations without losing their essential functionality.
Understanding the factors that contribute to network resilience is
crucial for predicting the response of biological systems to various
disturbances.
• Applications in Disease and Ecology: Percolation concepts have been
applied to study the spread of diseases in population networks and
the stability of ecological networks. For example, understanding how
the removal of certain species from an ecological network affects the
overall ecosystem structure.
Rewiring of network
• Network rewiring refers to the process of altering the connections (edges)
between nodes in a network.
• It is a systematic process of making changes to the network to achieve specific
goals, whether they are related to performance improvement, adaptation to new
conditions, or optimization
• This can be done for various reasons, such as optimizing network performance,
enhancing resilience, or studying the impact of structural changes on network
dynamics.
• In social networks, for example, rewiring may represent individuals forming or
severing connections.
• In biological networks, it could reflect the rewiring of molecular interactions. The
process of rewiring is essential for understanding how the structure of a network
influences its function and behavior
Rewiring of network
• The differential network flow (DNF) method to identify key regulators
of progression in development or disease.
• Given the network representation of consecutive biological states,
DNF quantifies the essentiality of each node by differences in the
distribution of network flow, which are capable of capturing
comprehensive topological differences from local to global feature
domains.
Rewiring of biological network
• It refers to the dynamic changes or alterations in the connections and
interactions among biological elements within a living organism.
• network can be a complex system of interconnected components, such as genes,
proteins, neurons, or other molecular and cellular entities.
• These networks play crucial roles in various biological processes, including
development, homeostasis, and response to environmental stimuli.
1. Neuronal Rewiring: In the nervous system, neural networks can undergo
rewiring through processes like synaptic plasticity. This involves the
strengthening or weakening of connections (synapses) between neurons in
response to experiences, learning, or changes in the environment
2. Gene Regulatory Networks:
3. Protein-Protein Interaction Networks:
4. Metabolic Networks: