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A Graphlet-Based Topological Characterization of the Resting-State Network in Healthy People.

ABSTRACT: In this paper, we propose a graphlet-based topological algorithm for the investigation of the brain network at resting state (RS). To this aim, we model the brain as a graph, where (labeled) nodes correspond to specific cerebral areas and links are weighted connections determined by the intensity of the functional magnetic resonance imaging (fMRI). Then, we select a number of working graphlets, namely, connected and non-isomorphic induced subgraphs. We compute, for each labeled node, its Graphlet Degree Vector (GDV), which allows us to associate a GDV matrix to each one of the 133 subjects of the considered sample, reporting how many times each node of the atlas "touches" the independent orbits defined by the graphlet set. We focus on the 56 independent columns (i.e., non-redundant orbits) of the GDV matrices. By aggregating their count all over the 133 subjects and then by sorting each column independently, we obtain a sorted node table, whose top-level entries highlight the nodes (i.e., brain regions) most frequently touching each of the 56 independent graphlet orbits. Then, by pairwise comparing the columns of the sorted node table in the top-k entries for various values of k, we identify sets of nodes that are consistently involved with high frequency in the 56 independent graphlet orbits all over the 133 subjects. It turns out that these sets consist of labeled nodes directly belonging to the default mode network (DMN) or strongly interacting with it at the RS, indicating that graphlet analysis provides a viable tool for the topological characterization of such brain regions. We finally provide a validation of the graphlet approach by testing its power in catching network differences. To this aim, we encode in a Graphlet Correlation Matrix (GCM) the network information associated with each subject then construct a subject-to-subject Graphlet Correlation Distance (GCD) matrix based on the Euclidean distances between all possible pairs of GCM. The analysis of the clusters induced by the GCD matrix shows a clear separation of the subjects in two groups, whose relationship with the subject characteristics is investigated.

SUBMITTER: Finotelli P

PROVIDER: S-EPMC8113409 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Discovering and understanding patterns in networks of protein-protein interactions (PPIs) is a central problem in systems biology. Alignments between these networks aid functional understanding as they uncover important information, such as evolutionary conserved pathways, protein complexes and functional orthologs. A few methods have been proposed for global PPI network alignments, but because of NP-completeness of underlying sub-graph isomorphism problem, producing topologically and biologically accurate alignments remains a challenge.We introduce a novel global network alignment tool, Lagrangian GRAphlet-based ALigner (L-GRAAL), which directly optimizes both the protein and the interaction functional conservations, using a novel alignment search heuristic based on integer programming and Lagrangian relaxation. We compare L-GRAAL with the state-of-the-art network aligners on the largest available PPI networks from BioGRID and observe that L-GRAAL uncovers the largest common sub-graphs between the networks, as measured by edge-correctness and symmetric sub-structures scores, which allow transferring more functional information across networks. We assess the biological quality of the protein mappings using the semantic similarity of their Gene Ontology annotations and observe that L-GRAAL best uncovers functionally conserved proteins. Furthermore, we introduce for the first time a measure of the semantic similarity of the mapped interactions and show that L-GRAAL also uncovers best functionally conserved interactions. In addition, we illustrate on the PPI networks of baker's yeast and human the ability of L-GRAAL to predict new PPIs. Finally, L-GRAAL's results are the first to show that topological information is more important than sequence information for uncovering functionally conserved interactions.L-GRAAL is coded in C++. Software is available at: http://bio-nets.doc.ic.ac.uk/L-GRAAL/.n.malod-dognin@imperial.ac.ukSupplementary data are available at Bioinformatics online.

Dataset Information

A Graphlet-Based Topological Characterization of the Resting-State Network in Healthy People.

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