63,479 research outputs found
Hierarchical modularity in human brain functional networks
The idea that complex systems have a hierarchical modular organization
originates in the early 1960s and has recently attracted fresh support from
quantitative studies of large scale, real-life networks. Here we investigate
the hierarchical modular (or "modules-within-modules") decomposition of human
brain functional networks, measured using functional magnetic resonance imaging
(fMRI) in 18 healthy volunteers under no-task or resting conditions. We used a
customized template to extract networks with more than 1800 regional nodes, and
we applied a fast algorithm to identify nested modular structure at several
hierarchical levels. We used mutual information, 0 < I < 1, to estimate the
similarity of community structure of networks in different subjects, and to
identify the individual network that is most representative of the group.
Results show that human brain functional networks have a hierarchical modular
organization with a fair degree of similarity between subjects, I=0.63. The
largest 5 modules at the highest level of the hierarchy were medial occipital,
lateral occipital, central, parieto-frontal and fronto-temporal systems;
occipital modules demonstrated less sub-modular organization than modules
comprising regions of multimodal association cortex. Connector nodes and hubs,
with a key role in inter-modular connectivity, were also concentrated in
association cortical areas. We conclude that methods are available for
hierarchical modular decomposition of large numbers of high resolution brain
functional networks using computationally expedient algorithms. This could
enable future investigations of Simon's original hypothesis that hierarchy or
near-decomposability of physical symbol systems is a critical design feature
for their fast adaptivity to changing environmental conditions
Graph Theory and Networks in Biology
In this paper, we present a survey of the use of graph theoretical techniques
in Biology. In particular, we discuss recent work on identifying and modelling
the structure of bio-molecular networks, as well as the application of
centrality measures to interaction networks and research on the hierarchical
structure of such networks and network motifs. Work on the link between
structural network properties and dynamics is also described, with emphasis on
synchronization and disease propagation.Comment: 52 pages, 5 figures, Survey Pape
Model of Brain Activation Predicts the Neural Collective Influence Map of the Brain
Efficient complex systems have a modular structure, but modularity does not
guarantee robustness, because efficiency also requires an ingenious interplay
of the interacting modular components. The human brain is the elemental
paradigm of an efficient robust modular system interconnected as a network of
networks (NoN). Understanding the emergence of robustness in such modular
architectures from the interconnections of its parts is a long-standing
challenge that has concerned many scientists. Current models of dependencies in
NoN inspired by the power grid express interactions among modules with fragile
couplings that amplify even small shocks, thus preventing functionality.
Therefore, we introduce a model of NoN to shape the pattern of brain
activations to form a modular environment that is robust. The model predicts
the map of neural collective influencers (NCIs) in the brain, through the
optimization of the influence of the minimal set of essential nodes responsible
for broadcasting information to the whole-brain NoN. Our results suggest new
intervention protocols to control brain activity by targeting influential
neural nodes predicted by network theory.Comment: 18 pages, 5 figure
Network-based stratification of tumor mutations.
Many forms of cancer have multiple subtypes with different causes and clinical outcomes. Somatic tumor genome sequences provide a rich new source of data for uncovering these subtypes but have proven difficult to compare, as two tumors rarely share the same mutations. Here we introduce network-based stratification (NBS), a method to integrate somatic tumor genomes with gene networks. This approach allows for stratification of cancer into informative subtypes by clustering together patients with mutations in similar network regions. We demonstrate NBS in ovarian, uterine and lung cancer cohorts from The Cancer Genome Atlas. For each tissue, NBS identifies subtypes that are predictive of clinical outcomes such as patient survival, response to therapy or tumor histology. We identify network regions characteristic of each subtype and show how mutation-derived subtypes can be used to train an mRNA expression signature, which provides similar information in the absence of DNA sequence
Identifying component modules
A computer-based system for modelling component dependencies and identifying component modules is presented. A variation of the Dependency Structure Matrix (DSM) representation was used to model component dependencies. The system utilises a two-stage approach towards facilitating the identification of a hierarchical modular structure. The first stage calculates a value for a clustering criterion that may be used to group component dependencies together. A Genetic Algorithm is described to optimise the order of the components within the DSM with the focus of minimising the value of the clustering criterion to identify the most significant component groupings (modules) within the product structure. The second stage utilises a 'Module Strength Indicator' (MSI) function to determine a value representative of the degree of modularity of the component groupings. The application of this function to the DSM produces a 'Module Structure Matrix' (MSM) depicting the relative modularity of available component groupings within it. The approach enabled the identification of hierarchical modularity in the product structure without the requirement for any additional domain specific knowledge within the system. The system supports design by providing mechanisms to explicitly represent and utilise component and dependency knowledge to facilitate the nontrivial task of determining near-optimal component modules and representing product modularity
Detection of regulator genes and eQTLs in gene networks
Genetic differences between individuals associated to quantitative phenotypic
traits, including disease states, are usually found in non-coding genomic
regions. These genetic variants are often also associated to differences in
expression levels of nearby genes (they are "expression quantitative trait
loci" or eQTLs for short) and presumably play a gene regulatory role, affecting
the status of molecular networks of interacting genes, proteins and
metabolites. Computational systems biology approaches to reconstruct causal
gene networks from large-scale omics data have therefore become essential to
understand the structure of networks controlled by eQTLs together with other
regulatory genes, and to generate detailed hypotheses about the molecular
mechanisms that lead from genotype to phenotype. Here we review the main
analytical methods and softwares to identify eQTLs and their associated genes,
to reconstruct co-expression networks and modules, to reconstruct causal
Bayesian gene and module networks, and to validate predicted networks in
silico.Comment: minor revision with typos corrected; review article; 24 pages, 2
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