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1. GRPhIN: Graphlet Characterization of Regulatory and Physical Interaction Networks

   https://doi.org/10.1093/bioadv/vbaf176  

   Barelvi, Altaf; Anderson, Oliver; Ritz, Anna (July 2025, Bioinformatics Advances)

   Shao, Mingfu (Ed.)

   Graphs are powerful tools for modeling and analyzing molecular interaction networks. Graphs typically represent either undirected physical interactions or directed regulatory relationships, which can obscure a particular protein’s functional context. Graphlets can describe local topologies and patterns within graphs, and combining physical and regulatory interactions offer new graphlet configurations that can provide biological insights. We present GRPhIN, a tool for characterizing graphlets and protein roles within graphlets in mixed physical and regulatory interaction networks. We describe the graphlets of mixed networks in B. subtilis, C. elegans, D. melanogaster, D. rerio, and S. cerevisiae and examine local topologies of proteins and subnetworks related to the oxidative stress response pathway. We found a number of graphlets that were abundant in all species, specific node positions (orbits) within graphlets that were over-represented in stress-associated proteins, and rarely-occurring graphlets that were over-represented in oxidative stress subnetworks. These results showcase the potential for using graphlets in mixed physical and regulatory interaction networks to identify new patterns beyond a single interaction type. 

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2. SoyCSN: Soybean context‐specific network analysis and prediction based on tissue‐specific transcriptome data

   https://doi.org/10.1002/pld3.167  

   Wang, Juexin; Hossain, Md Shakhawat; Lyu, Zhen; Schmutz, Jeremy; Stacey, Gary; Xu, Dong; Joshi, Trupti (September 2019, Plant Direct)

   Abstract The Soybean Gene Atlas project provides a comprehensive map for understanding gene expression patterns in major soybean tissues from flower, root, leaf, nodule, seed, and shoot and stem. The RNA‐Seq data generated in the project serve as a valuable resource for discovering tissue‐specific transcriptome behavior of soybean genes in different tissues. We developed a computational pipeline for Soybean context‐specific network (SoyCSN) inference with a suite of prediction tools to analyze, annotate, retrieve, and visualize soybean context‐specific networks at both transcriptome and interactome levels. BicMix and Cross‐Conditions Cluster Detection algorithms were applied to detect modules based on co‐expression relationships across all the tissues. Soybean context‐specific interactomes were predicted by combining soybean tissue gene expression and protein–protein interaction data. Functional analyses of these predicted networks provide insights into soybean tissue specificities. For example, under symbiotic, nitrogen‐fixing conditions, the constructed soybean leaf network highlights the connection between the photosynthesis function and rhizobium–legume symbiosis. SoyCSN data and all its results are publicly available via an interactive web service within the Soybean Knowledge Base (SoyKB) athttp://soykb.org/SoyCSN. SoyCSN provides a useful web‐based access for exploring context specificities systematically in gene regulatory mechanisms and gene relationships for soybean researchers and molecular breeders. 

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3. Multi-layer Bundling as a New Approach for Determining Multi-scale Correlations Within a High-Dimensional Dataset

   https://doi.org/10.1007/s11538-024-01335-8  

   Fazli, Mehran; Bertram, Richard; Striegel, Deborah_A (July 2024, Bulletin of Mathematical Biology)

   Abstract The growing complexity of biological data has spurred the development of innovative computational techniques to extract meaningful information and uncover hidden patterns within vast datasets. Biological networks, such as gene regulatory networks and protein-protein interaction networks, hold critical insights into biological features’ connections and functions. Integrating and analyzing high-dimensional data, particularly in gene expression studies, stands prominent among the challenges in deciphering these networks. Clustering methods play a crucial role in addressing these challenges, with spectral clustering emerging as a potent unsupervised technique considering intrinsic geometric structures. However, spectral clustering’s user-defined cluster number can lead to inconsistent and sometimes orthogonal clustering regimes. We propose theMulti-layer Bundling (MLB)method to address this limitation, combining multiple prominent clustering regimes to offer a comprehensive data view. We call the outcome clusters “bundles”. This approach refines clustering outcomes, unravels hierarchical organization, and identifies bridge elements mediating communication between network components. By layering clustering results, MLB provides a global-to-local view of biological feature clusters enabling insights into intricate biological systems. Furthermore, the method enhances bundle network predictions by integrating thebundle co-cluster matrixwith the affinity matrix. The versatility of MLB extends beyond biological networks, making it applicable to various domains where understanding complex relationships and patterns is needed. 

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4. Bio‐inspired human network diagnostics: Ecological modularity and nestedness as quantitative indicators of human engineered network function

   https://doi.org/10.1002/sys.21756  

   Blair, Samuel; Hairston, Garrett; Banks, Henry; Kaat, Claire; Linsey, Julie; Layton, Astrid (April 2024, Systems Engineering)

   Clifford Whitcomb (Ed.)

   Analyzing interactions between actors from a systems perspective yields valuable information about the overall system's form and function. When this is coupled with ecological modeling and analysis techniques, biological inspiration can also be applied to these systems. The diagnostic value of three metrics frequently used to study mutualistic biological ecosystems (nestedness, modularity, and connectance) is shown here using academic engineering makerspaces. Engineering students get hands‐on usage experience with tools for personal, class, and competition‐based projects in these spaces. COVID‐19 provides a unique study of university makerspaces, enabling the analysis of makerspace health through the known disturbance and resultant regulatory changes (implementation and return to normal operations). Nestedness, modularity, and connectance are shown to provide information on space functioning in a way that enables them to serve as heuristic diagnostics tools for system conditions. The makerspaces at two large R1 universities are analyzed across multiple semesters by modeling them as bipartite student‐tool interaction networks. The results visualize the predictive ability of these metrics, finding that the makerspaces tended to be structurally nested in any one semester, however when compared to a “normal” semester the restrictions are reflected via a higher modularity. The makerspace network case studies provide insight into the use and value of quantitative ecosystem structure and function indicators for monitoring similar human‐engineered interaction networks that are normally only tracked qualitatively. 

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5. Protein2Vec: Aligning Multiple PPI Networks with Representation Learning

   Jianliang Gao, Ling Tian (October 2019, IEEE/ACM transactions on computational biology and bioinformatics)

   Research of Protein-Protein Interaction (PPI) Network Alignment is playing an important role in understanding the crucial underlying biological knowledge such as functionally homologous proteins and conserved evolutionary pathways across different species. Existing methods of PPI network alignment often try to improve the coverage ratio of the alignment result by aligning all proteins from different species. However, there is a fundamental biological premise that needs to be considered carefully: not every protein in a species can, nor should, find its homologous proteins in other species. In this work, we propose a novel alignment method to map only those proteins with the most similarity throughout the PPI networks of multiple species. For the similarity features of the protein in the networks, we integrate both topological features with biological characteristics to provide enhanced supports for the alignment procedures. For topological features, we apply a representation learning method on the networks that can generate a low dimensional vector embedding with its surrounding structural features for each protein. The topological similarity of proteins from different PPI networks can thus be transferred as the similarity of their corresponding vector representations, which provides a new way to comprehensively quantify the topological similarities between proteins. We also propose a new measure for the topological evaluation of the alignment results which better uncover the structural quality of the alignment across multiple networks. Both biological and topological evaluations on the alignment results of real datasets demonstrate our approach is promising and preferable against previous multiple alignment methods 

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