204,213 research outputs found
Revealing networks from dynamics: an introduction
What can we learn from the collective dynamics of a complex network about its
interaction topology? Taking the perspective from nonlinear dynamics, we
briefly review recent progress on how to infer structural connectivity (direct
interactions) from accessing the dynamics of the units. Potential applications
range from interaction networks in physics, to chemical and metabolic
reactions, protein and gene regulatory networks as well as neural circuits in
biology and electric power grids or wireless sensor networks in engineering.
Moreover, we briefly mention some standard ways of inferring effective or
functional connectivity.Comment: Topical review, 48 pages, 7 figure
Comparison and validation of community structures in complex networks
The issue of partitioning a network into communities has attracted a great
deal of attention recently. Most authors seem to equate this issue with the one
of finding the maximum value of the modularity, as defined by Newman. Since the
problem formulated this way is NP-hard, most effort has gone into the
construction of search algorithms, and less to the question of other measures
of community structures, similarities between various partitionings and the
validation with respect to external information. Here we concentrate on a class
of computer generated networks and on three well-studied real networks which
constitute a bench-mark for network studies; the karate club, the US college
football teams and a gene network of yeast. We utilize some standard ways of
clustering data (originally not designed for finding community structures in
networks) and show that these classical methods sometimes outperform the newer
ones. We discuss various measures of the strength of the modular structure, and
show by examples features and drawbacks. Further, we compare different
partitions by applying some graph-theoretic concepts of distance, which
indicate that one of the quality measures of the degree of modularity
corresponds quite well with the distance from the true partition. Finally, we
introduce a way to validate the partitionings with respect to external data
when the nodes are classified but the network structure is unknown. This is
here possible since we know everything of the computer generated networks, as
well as the historical answer to how the karate club and the football teams are
partitioned in reality. The partitioning of the gene network is validated by
use of the Gene Ontology database, where we show that a community in general
corresponds to a biological process.Comment: To appear in Physica A; 25 page
A stochastic and dynamical view of pluripotency in mouse embryonic stem cells
Pluripotent embryonic stem cells are of paramount importance for biomedical
research thanks to their innate ability for self-renewal and differentiation
into all major cell lines. The fateful decision to exit or remain in the
pluripotent state is regulated by complex genetic regulatory network. Latest
advances in transcriptomics have made it possible to infer basic topologies of
pluripotency governing networks. The inferred network topologies, however, only
encode boolean information while remaining silent about the roles of dynamics
and molecular noise in gene expression. These features are widely considered
essential for functional decision making. Herein we developed a framework for
extending the boolean level networks into models accounting for individual
genetic switches and promoter architecture which allows mechanistic
interrogation of the roles of molecular noise, external signaling, and network
topology. We demonstrate the pluripotent state of the network to be a broad
attractor which is robust to variations of gene expression. Dynamics of exiting
the pluripotent state, on the other hand, is significantly influenced by the
molecular noise originating from genetic switching events which makes cells
more responsive to extracellular signals. Lastly we show that steady state
probability landscape can be significantly remodeled by global gene switching
rates alone which can be taken as a proxy for how global epigenetic
modifications exert control over stability of pluripotent states.Comment: 11 pages, 7 figure
Recommended from our members
GenEpi: gene-based epistasis discovery using machine learning.
BackgroundGenome-wide association studies (GWAS) provide a powerful means to identify associations between genetic variants and phenotypes. However, GWAS techniques for detecting epistasis, the interactions between genetic variants associated with phenotypes, are still limited. We believe that developing an efficient and effective GWAS method to detect epistasis will be a key for discovering sophisticated pathogenesis, which is especially important for complex diseases such as Alzheimer's disease (AD).ResultsIn this regard, this study presents GenEpi, a computational package to uncover epistasis associated with phenotypes by the proposed machine learning approach. GenEpi identifies both within-gene and cross-gene epistasis through a two-stage modeling workflow. In both stages, GenEpi adopts two-element combinatorial encoding when producing features and constructs the prediction models by L1-regularized regression with stability selection. The simulated data showed that GenEpi outperforms other widely-used methods on detecting the ground-truth epistasis. As real data is concerned, this study uses AD as an example to reveal the capability of GenEpi in finding disease-related variants and variant interactions that show both biological meanings and predictive power.ConclusionsThe results on simulation data and AD demonstrated that GenEpi has the ability to detect the epistasis associated with phenotypes effectively and efficiently. The released package can be generalized to largely facilitate the studies of many complex diseases in the near future
Knowledge Rich Natural Language Queries over Structured Biological Databases
Increasingly, keyword, natural language and NoSQL queries are being used for
information retrieval from traditional as well as non-traditional databases
such as web, document, image, GIS, legal, and health databases. While their
popularity are undeniable for obvious reasons, their engineering is far from
simple. In most part, semantics and intent preserving mapping of a well
understood natural language query expressed over a structured database schema
to a structured query language is still a difficult task, and research to tame
the complexity is intense. In this paper, we propose a multi-level
knowledge-based middleware to facilitate such mappings that separate the
conceptual level from the physical level. We augment these multi-level
abstractions with a concept reasoner and a query strategy engine to dynamically
link arbitrary natural language querying to well defined structured queries. We
demonstrate the feasibility of our approach by presenting a Datalog based
prototype system, called BioSmart, that can compute responses to arbitrary
natural language queries over arbitrary databases once a syntactic
classification of the natural language query is made
A survey of QoS-aware web service composition techniques
Web service composition can be briefly described as the process of aggregating services with disparate functionalities into a new composite service in order to meet increasingly complex needs of users. Service composition process has been accurate on dealing with services having disparate functionalities, however, over the years the number of web services in particular that exhibit similar functionalities and varying Quality of Service (QoS) has significantly increased. As such, the problem becomes how to select appropriate web services such that the QoS of the resulting composite service is maximized or, in some cases, minimized. This constitutes an NP-hard problem as it is complicated and difficult to solve. In this paper, a discussion of concepts of web service composition and a holistic review of current service composition techniques proposed in literature is presented. Our review spans several publications in the field that can serve as a road map for future research
The cultural epigenetics of psychopathology: The missing heritability of complex diseases found?
We extend a cognitive paradigm for gene expression based on the asymptotic limit theorems of information theory to the epigenetic epidemiology of mental disorders. In particular, we recognize the fundamental role culture plays in human biology, another heritage mechanism parallel to, and interacting with, the more familiar genetic and epigenetic systems. We do this via a model through which culture acts as another tunable epigenetic catalyst that both directs developmental trajectories, and becomes convoluted with individual ontology, via a mutually-interacting crosstalk mediated by a social interaction that is itself culturally driven. We call for the incorporation of embedding culture as an essential component of the epigenetic regulation of human mental development and its dysfunctions, bringing what is perhaps the central reality of human biology into the center of biological psychiatry. Current US work on gene-environment interactions in psychiatry must be extended to a model of gene-environment-culture interaction to avoid becoming victim of an extreme American individualism that threatens to create paradigms particular to that culture and that are, indeed, peculiar in the context of the world's cultures. The cultural and epigenetic systems of heritage may well provide the 'missing' heritability of complex diseases now under so much intense discussion
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