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Community detection in network analysis: a survey
The existence of community structures in networks is not unusual, including in the domains of sociology, biology, and business, etc. The characteristic of the community structure is that nodes of the same community are highly similar while on the contrary, nodes across communities present low similarity.
In academia, there is a surge in research efforts on community detection in network analysis, especially in developing statistically sound methodologies for exploring, modeling, and interpreting these kind of structures and relationships.
This survey paper aims to provide a brief review of current applicable
statistical methodologies and approaches in a comparative manner along with metrics for evaluating graph clustering results and application using R. At the
end, we provide promising future research directions.Statistic
Node similarity within subgraphs of protein interaction networks
We propose a biologically motivated quantity, twinness, to evaluate local
similarity between nodes in a network. The twinness of a pair of nodes is the
number of connected, labeled subgraphs of size n in which the two nodes possess
identical neighbours. The graph animal algorithm is used to estimate twinness
for each pair of nodes (for subgraph sizes n=4 to n=12) in four different
protein interaction networks (PINs). These include an Escherichia coli PIN and
three Saccharomyces cerevisiae PINs -- each obtained using state-of-the-art
high throughput methods. In almost all cases, the average twinness of node
pairs is vastly higher than expected from a null model obtained by switching
links. For all n, we observe a difference in the ratio of type A twins (which
are unlinked pairs) to type B twins (which are linked pairs) distinguishing the
prokaryote E. coli from the eukaryote S. cerevisiae. Interaction similarity is
expected due to gene duplication, and whole genome duplication paralogues in S.
cerevisiae have been reported to co-cluster into the same complexes. Indeed, we
find that these paralogous proteins are over-represented as twins compared to
pairs chosen at random. These results indicate that twinness can detect
ancestral relationships from currently available PIN data.Comment: 10 pages, 5 figures. Edited for typos, clarity, figures improved for
readabilit
SWIM: A computational tool to unveiling crucial nodes in complex biological networks
SWItchMiner (SWIM) is a wizard-like software implementation of a procedure, previously described, able to extract information contained in complex networks. Specifically, SWIM allows unearthing the existence of a new class of hubs, called "fight-club hubs", characterized by a marked negative correlation with their first nearest neighbors. Among them, a special subset of genes, called "switch genes", appears to be characterized by an unusual pattern of intra- and inter-module connections that confers them a crucial topological role, interestingly mirrored by the evidence of their clinic-biological relevance. Here, we applied SWIM to a large panel of cancer datasets from The Cancer Genome Atlas, in order to highlight switch genes that could be critically associated with the drastic changes in the physiological state of cells or tissues induced by the cancer development. We discovered that switch genes are found in all cancers we studied and they encompass protein coding genes and non-coding RNAs, recovering many known key cancer players but also many new potential biomarkers not yet characterized in cancer context. Furthermore, SWIM is amenable to detect switch genes in different organisms and cell conditions, with the potential to uncover important players in biologically relevant scenarios, including but not limited to human cancer
Characterization of complex networks: A survey of measurements
Each complex network (or class of networks) presents specific topological
features which characterize its connectivity and highly influence the dynamics
of processes executed on the network. The analysis, discrimination, and
synthesis of complex networks therefore rely on the use of measurements capable
of expressing the most relevant topological features. This article presents a
survey of such measurements. It includes general considerations about complex
network characterization, a brief review of the principal models, and the
presentation of the main existing measurements. Important related issues
covered in this work comprise the representation of the evolution of complex
networks in terms of trajectories in several measurement spaces, the analysis
of the correlations between some of the most traditional measurements,
perturbation analysis, as well as the use of multivariate statistics for
feature selection and network classification. Depending on the network and the
analysis task one has in mind, a specific set of features may be chosen. It is
hoped that the present survey will help the proper application and
interpretation of measurements.Comment: A working manuscript with 78 pages, 32 figures. Suggestions of
measurements for inclusion are welcomed by the author
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Mapping genetic interactions in cancer: a road to rational combination therapies.
The discovery of synthetic lethal interactions between poly (ADP-ribose) polymerase (PARP) inhibitors and BRCA genes, which are involved in homologous recombination, led to the approval of PARP inhibition as a monotherapy for patients with BRCA1/2-mutated breast or ovarian cancer. Studies following the initial observation of synthetic lethality demonstrated that the reach of PARP inhibitors is well beyond just BRCA1/2 mutants. Insights into the mechanisms of action of anticancer drugs are fundamental for the development of targeted monotherapies or rational combination treatments that will synergize to promote cancer cell death and overcome mechanisms of resistance. The development of targeted therapeutic agents is premised on mapping the physical and functional dependencies of mutated genes in cancer. An important part of this effort is the systematic screening of genetic interactions in a variety of cancer types. Until recently, genetic-interaction screens have relied either on the pairwise perturbations of two genes or on the perturbation of genes of interest combined with inhibition by commonly used anticancer drugs. Here, we summarize recent advances in mapping genetic interactions using targeted, genome-wide, and high-throughput genetic screens, and we discuss the therapeutic insights obtained through such screens. We further focus on factors that should be considered in order to develop a robust analysis pipeline. Finally, we discuss the integration of functional interaction data with orthogonal methods and suggest that such approaches will increase the reach of genetic-interaction screens for the development of rational combination therapies
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