2,101 research outputs found
LASAGNE: Locality And Structure Aware Graph Node Embedding
In this work we propose Lasagne, a methodology to learn locality and
structure aware graph node embeddings in an unsupervised way. In particular, we
show that the performance of existing random-walk based approaches depends
strongly on the structural properties of the graph, e.g., the size of the
graph, whether the graph has a flat or upward-sloping Network Community Profile
(NCP), whether the graph is expander-like, whether the classes of interest are
more k-core-like or more peripheral, etc. For larger graphs with flat NCPs that
are strongly expander-like, existing methods lead to random walks that expand
rapidly, touching many dissimilar nodes, thereby leading to lower-quality
vector representations that are less useful for downstream tasks. Rather than
relying on global random walks or neighbors within fixed hop distances, Lasagne
exploits strongly local Approximate Personalized PageRank stationary
distributions to more precisely engineer local information into node
embeddings. This leads, in particular, to more meaningful and more useful
vector representations of nodes in poorly-structured graphs. We show that
Lasagne leads to significant improvement in downstream multi-label
classification for larger graphs with flat NCPs, that it is comparable for
smaller graphs with upward-sloping NCPs, and that is comparable to existing
methods for link prediction tasks
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
Network reconstruction of platelet metabolism identifies metabolic signature for aspirin resistance.
Recently there has not been a systematic, objective assessment of the metabolic capabilities of the human platelet. A manually curated, functionally tested, and validated biochemical reaction network of platelet metabolism, iAT-PLT-636, was reconstructed using 33 proteomic datasets and 354 literature references. The network contains enzymes mapping to 403 diseases and 231 FDA approved drugs, alluding to an expansive scope of biochemical transformations that may affect or be affected by disease processes in multiple organ systems. The effect of aspirin (ASA) resistance on platelet metabolism was evaluated using constraint-based modeling, which revealed a redirection of glycolytic, fatty acid, and nucleotide metabolism reaction fluxes in order to accommodate eicosanoid synthesis and reactive oxygen species stress. These results were confirmed with independent proteomic data. The construction and availability of iAT-PLT-636 should stimulate further data-driven, systems analysis of platelet metabolism towards the understanding of pathophysiological conditions including, but not strictly limited to, coagulopathies
Decreased thalamo-cortico connectivity during an implicit sequence motor learning task and 7 days escitalopram intake
Evidence suggests that selective serotonin reuptake inhibitors (SSRIs) reorganize neural networks via a transient window of neuroplasticity. While previous findings support an effect of SSRIs on intrinsic functional connectivity, little is known regarding the influence of SSRI-administration on connectivity during sequence motor learning. To investigate this, we administered 20 mg escitalopram or placebo for 1-week to 60 healthy female participants undergoing concurrent functional magnetic resonance imaging and sequence motor training in a double-blind randomized controlled design. We assessed task-modulated functional connectivity with a psycho-physiological interaction (PPI) analysis in the thalamus, putamen, cerebellum, dorsal premotor, primary motor, supplementary motor, and dorsolateral prefrontal cortices. Comparing an implicit sequence learning condition to a control learning condition, we observed decreased connectivity between the thalamus and bilateral motor regions after 7 days of escitalopram intake. Additionally, we observed a negative correlation between plasma escitalopram levels and PPI connectivity changes, with higher escitalopram levels being associated with greater thalamo-cortico decreases. Our results suggest that escitalopram enhances network-level processing efficiency during sequence motor learning, despite no changes in behaviour. Future studies in more diverse samples, however, with quantitative imaging of neurochemical markers of excitation and inhibition, are necessary to further assess neural responses to escitalopram
Controllability of protein-protein interaction phosphorylation-based networks: Participation of the hub 14-3-3 protein family
Posttranslational regulation of protein function is an ubiquitous mechanism in eukaryotic cells. Here, we analyzed biological properties of nodes and edges of a human protein-protein interaction phosphorylation-based network, especially of those nodes critical for the network controllability. We found that the minimal number of critical nodes needed to control the whole network is 29%, which is considerably lower compared to other real networks. These critical nodes are more regulated by posttranslational modifications and contain more binding domains to these modifications than other kinds of nodes in the network, suggesting an intra-group fast regulation. Also, when we analyzed the edges characteristics that connect critical and non-critical nodes, we found that the former are enriched in domain-to-eukaryotic linear motif interactions, whereas the later are enriched in domain-domain interactions. Our findings suggest a possible structure for protein-protein interaction networks with a densely interconnected and self-regulated central core, composed of critical nodes with a high participation in the controllability of the full network, and less regulated peripheral nodes. Our study offers a deeper understanding of complex network control and bridges the controllability theorems for complex networks and biological protein-protein interaction phosphorylation-based networked systems.Fil: Uhart, Marina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Flores, Gabriel. Eventioz/eventbrite Company; ArgentinaFil: Bustos, Diego Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentin
Toward a greater understanding of the brain processes underlying handgrip and handgrip fatigue
Handgrip is a ubiquitous human movement that determines how we interact with our environment. It is involved in almost every aspect of daily life (e.g. opening a door, handling cutlery, using tools) and like all human movement, its application is limited by muscle fatigue. However, the supraspinal mechanisms of handgrip and handgrip fatigue are not fully understood despite the importance of this fundamental movement, numerous publications, and its presence as a longstanding research topic. This thesis investigates the brain mechanisms of handgrip and handgrip fatigue using fMRI. It begins with a review of the literature in Chapter one, which evaluates the theories and evidence for central control of handgrip and muscle fatigue as well as describing the rationale to perform the experiments in this thesis. The methodology and analyses are also reviewed to provide rationale for their use and to facilitate the interpretation of subsequent experimental results. In order to understand the supraspinal mechanisms of handgrip and handgrip fatigue it is logical to first understand the most fundamental grip type (power vs. precision) and pattern (static vs. dynamic) by which handgrip can be performed
Profiling core-periphery network structure by random walkers
Disclosing the main features of the structure of a network is crucial to understand a number of static and dynamic properties, such as robustness to failures, spreading dynamics, or collective behaviours. Among the possible characterizations, the core-periphery paradigm models the network as the union of a dense core with a sparsely connected periphery, highlighting the role of each node on the basis of its topological position. Here we show that the core-periphery structure can effectively be profiled by elaborating the behaviour of a random walker. A curve—the core-periphery profile—and a numerical indicator are derived, providing a global topological portrait. Simultaneously, a coreness value is attributed to each node, qualifying its position and role. The application to social, technological, economical, and biological networks reveals the power of this technique in disclosing the overall network structure and the peculiar role of some specific nodes
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