Hierarchical communities in the larval Drosophila connectome: Links to cellular annotations and network topology.

One of the longstanding aims of network neuroscience is to link a connectome's topological properties-i.e., features defined from connectivity alone-with an organism's neurobiology. One approach for doing so is to compare connectome properties with annotational maps. This type of analysis is popular at the meso-/macroscale, but is less common at the nano-scale, owing to a paucity of neuron-level connectome data. However, recent methodological advances have made possible the reconstruction of whole-brain connectomes at single-neuron resolution for a select set of organisms. These include the fruit fly, Drosophila melanogaster, and its developing larvae. In addition to fine-scale descriptions of connectivity, these datasets are accompanied by rich annotations. Here, we use a variant of the stochastic blockmodel to detect multilevel communities in the larval Drosophila connectome. We find that communities partition neurons based on function and cell type and that most interact assortatively, reflecting the principle of functional segregation. However, a small number of communities interact nonassortatively, forming form a "rich-club" of interneurons that receive sensory/ascending inputs and deliver outputs along descending pathways. Next, we investigate the role of community structure in shaping communication patterns. We find that polysynaptic signaling follows specific trajectories across modular hierarchies, with interneurons playing a key role in mediating communication routes between modules and hierarchical scales. Our work suggests a relationship between system-level architecture and the biological function and classification of individual neurons. We envision our study as an important step toward bridging the gap between complex systems and neurobiological lines of investigation in brain sciences.

Network physics of attractive colloidal gels: Resilience, rigidity, and phase diagram.

Colloidal gels exhibit solid-like behavior at vanishingly small fractions of solids, owing to ramified space-spanning networks that form due to particle-particle interactions. These networks give the gel its rigidity, and with stronger attractions the elasticity grows as well. The emergence of rigidity can be described through a mean field approach; nonetheless, fundamental understanding of how rigidity varies in gels of different attractions is lacking. Moreover, recovering an accurate gelation phase diagram based on the system's variables has been an extremely challenging task. Understanding the nature of colloidal clusters, and how rigidity emerges from their connections is key to controlling and designing gels with desirable properties. Here, we employ network analysis tools to interrogate and characterize the colloidal structures. We construct a particle-level network, having all the spatial coordinates of colloids with different attraction levels, and also identify polydisperse rigid fractal clusters using a Gaussian mixture model, to form a coarse-grained cluster network that distinctly shows main physical features of the colloidal gels. A simple mass-spring model then is used to recover quantitatively the elasticity of colloidal gels from these cluster networks. Interrogating the resilience of these gel networks shows that the elasticity of a gel (a dynamic property) is directly correlated to its cluster network's resilience (a static measure). Finally, we use the resilience investigations to devise [and experimentally validate] a fully resolved phase diagram for colloidal gelation, with a clear solid-liquid phase boundary using a single volume fraction of particles well beyond this phase boundary.

Noncoding RNAs improve the predictive power of network medicine.

Network medicine has improved the mechanistic understanding of disease, offering quantitative insights into disease mechanisms, comorbidities, and novel diagnostic tools and therapeutic treatments. Yet, most network-based approaches rely on a comprehensive map of protein-protein interactions (PPI), ignoring interactions mediated by noncoding RNAs (ncRNAs). Here, we systematically combine experimentally confirmed binding interactions mediated by ncRNA with PPI, constructing a comprehensive network of all physical interactions in the human cell. We find that the inclusion of ncRNA expands the number of genes in the interactome by 46% and the number of interactions by 107%, significantly enhancing our ability to identify disease modules. Indeed, we find that 132 diseases lacked a statistically significant disease module in the protein-based interactome but have a statistically significant disease module after inclusion of ncRNA-mediated interactions, making these diseases accessible to the tools of network medicine. We show that the inclusion of ncRNAs helps unveil disease-disease relationships that were not detectable before and expands our ability to predict comorbidity patterns between diseases. Taken together, we find that including noncoding interactions improves both the breath and the predictive accuracy of network medicine.

Decoding the Foodome: Molecular Networks Connecting Diet and Health.

Diet, a modifiable risk factor, plays a pivotal role in most diseases, from cardiovascular disease to type 2 diabetes mellitus, cancer, and obesity. However, our understanding of the mechanistic role of the chemical compounds found in food remains incomplete. In this review, we explore the "dark matter" of nutrition, going beyond the macro- and micronutrients documented by national databases to unveil the exceptional chemical diversity of food composition. We also discuss the need to explore the impact of each compound in the presence of associated chemicals and relevant food sources and describe the tools that will allow us to do so. Finally, we discuss the role of network medicine in understanding the mechanism of action of each food molecule. Overall, we illustrate the important role of network science and artificial intelligence in our ability to reveal nutrition's multifaceted role in health and disease.

Neuroscience Needs Network Science.

The brain is a complex system comprising a myriad of interacting neurons, posing significant challenges in understanding its structure, function, and dynamics. Network science has emerged as a powerful tool for studying such interconnected systems, offering a framework for integrating multiscale data and complexity. To date, network methods have significantly advanced functional imaging studies of the human brain and have facilitated the development of control theory-based applications for directing brain activity. Here, we discuss emerging frontiers for network neuroscience in the brain atlas era, addressing the challenges and opportunities in integrating multiple data streams for understanding the neural transitions from development to healthy function to disease. We underscore the importance of fostering interdisciplinary opportunities through workshops, conferences, and funding initiatives, such as supporting students and postdoctoral fellows with interests in both disciplines. By bringing together the network science and neuroscience communities, we can develop novel network-based methods tailored to neural circuits, paving the way toward a deeper understanding of the brain and its functions, as well as offering new challenges for network science.

Coalitions in international litigation: a network perspective.

We apply network science principles to analyse the coalitions formed by European Union nations and institutions during litigation proceedings at the European Court of Justice. By constructing Friends and Foes networks, we explore their characteristics and dynamics through the application of cluster detection, motif analysis and duplex analysis. Our findings demonstrate that the Friends and Foes networks exhibit disassortative behaviour, highlighting the inclination of nodes to connect with dissimilar nodes. Furthermore, there is a correlation among centrality measures, indicating that member states and institutions with a larger number of connections play a prominent role in bridging the network. An examination of the modularity of the networks reveals that coalitions tend to align along regional and institutional lines, rather than national government divisions. Additionally, an analysis of triadic binary motifs uncovers a greater level of reciprocity within the Foes network compared to the Friends network. This article is part of the theme issue 'A complexity science approach to law and governance'.

Predicting the SARS-CoV-2 effective reproduction number using bulk contact data from mobile phones.

Over the last months, cases of SARS-CoV-2 surged repeatedly in many countries but could often be controlled with nonpharmaceutical interventions including social distancing. We analyzed deidentified Global Positioning System (GPS) tracking data from 1.15 to 1.4 million cell phones in Germany per day between March and November 2020 to identify encounters between individuals and statistically evaluate contact behavior. Using graph sampling theory, we estimated the contact index (CX), a metric for number and heterogeneity of contacts. We found that CX, and not the total number of contacts, is an accurate predictor for the effective reproduction number R derived from case numbers. A high correlation between CX and R recorded more than 2 wk later allows assessment of social behavior well before changes in case numbers become detectable. By construction, the CX quantifies the role of superspreading and permits assigning risks to specific contact behavior. We provide a critical CX value beyond which R is expected to rise above 1 and propose to use that value to leverage the social-distancing interventions for the coming months.

Emergence of hierarchy in networked endorsement dynamics.

Many social and biological systems are characterized by enduring hierarchies, including those organized around prestige in academia, dominance in animal groups, and desirability in online dating. Despite their ubiquity, the general mechanisms that explain the creation and endurance of such hierarchies are not well understood. We introduce a generative model for the dynamics of hierarchies using time-varying networks, in which new links are formed based on the preferences of nodes in the current network and old links are forgotten over time. The model produces a range of hierarchical structures, ranging from egalitarianism to bistable hierarchies, and we derive critical points that separate these regimes in the limit of long system memory. Importantly, our model supports statistical inference, allowing for a principled comparison of generative mechanisms using data. We apply the model to study hierarchical structures in empirical data on hiring patterns among mathematicians, dominance relations among parakeets, and friendships among members of a fraternity, observing several persistent patterns as well as interpretable differences in the generative mechanisms favored by each. Our work contributes to the growing literature on statistically grounded models of time-varying networks.

Feats: A database of semantic features for early produced noun concepts.

Semantic feature production norms have several desirable characteristics that have supported models of representation and processing in adults. However, several key challenges have limited the use of semantic feature norms in studies of early language acquisition. First, existing norms provide uneven and inconsistent coverage of early-acquired concepts that are typically produced and assessed in children under the age of three, which is a time of tremendous growth of early vocabulary skills. Second, it is difficult to assess the degree to which young children may be familiar with normed features derived from these adult-generated datasets. Third, it has been difficult to adopt standard methods to generate semantic network models of early noun learning. Here, we introduce Feats-a tool that was designed to make headway on these challenges by providing a database, the Language Learning and Meaning Acquisition (LLaMA) lab Noun Norms that extends a widely used set of feature norms McRae et al. Behavior Research Methods 37, 547-559, (2005) to include full coverage of noun concepts on a commonly used early vocabulary assessment. Feats includes several tools to facilitate exploration of features comprising early-acquired nouns, assess the developmental appropriateness of individual features using toddler-accessibility norms, and extract semantic network statistics for individual vocabulary profiles. We provide a tutorial overview of Feats. We additionally validate our approach by presenting an analysis of an overlapping set of concepts collected across prior and new data collection methods. Furthermore, using network graph analyses, we show that the extended set of norms provides novel, reliable results given their enhanced coverage.

Decoding the News Media Diet of Disinformation Spreaders.

In the digital era, information consumption is predominantly channeled through online news media and disseminated on social media platforms. Understanding the complex dynamics of the news media environment and users' habits within the digital ecosystem is a challenging task that requires, at the same time, large databases and accurate methodological approaches. This study contributes to this expanding research landscape by employing network science methodologies and entropic measures to analyze the behavioral patterns of social media users sharing news pieces and dig into the diverse news consumption habits within different online social media user groups. Our analyses reveal that users are more inclined to share news classified as fake when they have previously posted conspiracy or junk science content and vice versa, creating a series of "misinformation hot streaks". To better understand these dynamics, we used three different measures of entropy to gain insights into the news media habits of each user, finding that the patterns of news consumption significantly differ among users when focusing on disinformation spreaders as opposed to accounts sharing reliable or low-risk content. Thanks to these entropic measures, we quantify the variety and the regularity of the news media diet, finding that those disseminating unreliable content exhibit a more varied and, at the same time, a more regular choice of web-domains. This quantitative insight into the nuances of news consumption behaviors exhibited by disinformation spreaders holds the potential to significantly inform the strategic formulation of more robust and adaptive social media moderation policies.

[Network science. Part 2 : in radiotherapy]. / La science des réseaux. Partie 2 : en radiothérapie.

In a former publication, we summarized basic principles of network science in order to understand its potential, especially within the field of oncology. This rather young science offers, for example, the opportunity to identify new systemic treatment options. However, these are not the only therapeutic options within the arsenal devoted to the battle against cancer. The two other main pillars of treatment are surgery and radiotherapy. It is our purpose to highlight some applications - rather limited nowadays - of network science in radiotherapy. Data are not so abundant compared to the field of systemic treatments.

Dans un article précédent, les préceptes de base de la science des réseaux ont été sommairement abordés, afin d'en illustrer l'intérêt en cancérologie, en général. Nous avons pu faire le point - de façon non exhaustive - sur l'utilité de cette science assez jeune, en montrant, par exemple, son apport en matière d'identification de moyens systémiques de traitement. Les traitements systémiques font partie de l'arsenal thérapeutique, tout comme d'ailleurs la chirurgie et la radiothérapie. Nous voulons décrire brièvement certaines applications de la science des réseaux quand il s'agit du domaine particulier des radiations ionisantes, même si leur nombre est somme toute plus limité par rapport à ce qui est publié dans le domaine des traitements systémiques.

[Network science. Part 1 : in oncology in general]. / La science des réseaux. Partie 1 : en cancérologie, en général.

The overwhelming avalanche of data issued from the omics cascade, and particularly the mapping of protein-protein interaction (interactome), allows us to dissect the complexity and overlapping of diseases, as well as their management. With the help of theoretical and scientific bases issued form network science, as well as the rapid evolution of artificial intelligence, in particular machine learning (with its high speed and capacity), we are able today to uncover new driver genes, new biomarkers, new interactions with diagnostic and therapeutic modalities (even for an individual patient). It also opens new perspectives in the fields of prediction of response to treatment as well as prevention. The expectations are particularly high and diverse in health care. We take stock non-exhaustively on some applications in the field of oncology.

L'avalanche des données issues de la cascade des «omics¼, et en particulier la cartographie des interactions protéine-protéine (l'interactome), permettent aujourd'hui - grâce aux bases théoriques et scientifiques établies dans la science des réseaux, et aux développements rapides en intelligence artificielle, en particulier en «machine learning¼ (avec sa rapidité et sa puissance de calcul) - de disséquer la complexité et la superposition des maladies, ainsi que leur prise en charge. Ceci nous permet également de découvrir de nouveaux gènes clé, de nouveaux biomarqueurs, de nouvelles interactions avec des modalités tant thérapeutiques que diagnostiques (y compris adaptées à l'individu), et nous ouvre de nouvelles perspectives dans les domaines de la prédiction (de la réponse à un traitement) et de la prévention. Les attentes sont donc multiples dans le domaine de la santé. Nous faisons le point - de façon non exhaustive - sur certaines applications dans le domaine particulier de l'oncologie.

Network-based artificial intelligence approaches for advancing personalized psychiatry.

Psychiatric disorders have a complex biological underpinning likely involving an interplay of genetic and environmental risk contributions. Substantial efforts are being made to use artificial intelligence approaches to integrate features within and across data types to increase our etiological understanding and advance personalized psychiatry. Network science offers a conceptual framework for exploring the often complex relationships across different levels of biological organization, from cellular mechanistic to brain-functional and phenotypic networks. Utilizing such network information effectively as part of artificial intelligence approaches is a promising route toward a more in-depth understanding of illness biology, the deciphering of patient heterogeneity, and the identification of signatures that may be sufficiently predictive to be clinically useful. Here, we present examples of how network information has been used as part of artificial intelligence within psychiatry and beyond and outline future perspectives on how personalized psychiatry approaches may profit from a closer integration of psychiatric research, artificial intelligence development, and network science.

Divergent Histopathological Networks of Frontotemporal Degeneration Proteinopathy Subytpes.

Network analyses inform complex systems such as human brain connectivity, but this approach is seldom applied to gold-standard histopathology. Here, we use two complimentary computational approaches to model microscopic progression of the main subtypes of tauopathy versus TDP-43 proteinopathy in the human brain. Digital histopathology measures were obtained in up to 13 gray matter (GM) and adjacent white matter (WM) cortical brain regions sampled from 53 tauopathy and 66 TDP-43 proteinopathy autopsy patients. First, we constructed a weighted non-directed graph for each group, where nodes are defined as GM and WM regions sampled and edges in the graph are weighted using the group-level Pearson's correlation coefficient for each pairwise node comparison. Additionally, we performed mediation analyses to test mediation effects of WM pathology between anterior frontotemporal and posterior parietal GM nodes. We find greater correlation (i.e., edges) between GM and WM node pairs in tauopathies compared with TDP-43 proteinopathies. Moreover, WM pathology strongly correlated with a graph metric of pathology spread (i.e., node-strength) in tauopathies (r = 0.60, p < 0.03) but not in TDP-43 proteinopathies (r = 0.03, p = 0.9). Finally, we found mediation effects for WM pathology on the association between anterior and posterior GM pathology in FTLD-Tau but not in FTLD-TDP. These data suggest distinct tau and TDP-43 proteinopathies may have divergent patterns of cellular propagation in GM and WM. More specifically, axonal spread may be more influential in FTLD-Tau progression. Network analyses of digital histopathological measurements can inform models of disease progression of cellular degeneration in the human brain.SIGNIFICANCE STATEMENT In this study, we uniquely perform two complimentary computational approaches to model and contrast microscopic disease progression between common frontotemporal lobar degeneration (FTLD) proteinopathy subtypes with similar clinical syndromes during life. Our models suggest white matter (WM) pathology influences cortical spread of disease in tauopathies that is less evident in TDP-43 proteinopathies. These data support the hypothesis that there are neuropathologic signatures of cellular degeneration within neurocognitive networks for specific protienopathies. These distinctive patterns of cellular pathology can guide future efforts to develop tissue-sensitive imaging and biological markers with diagnostic and prognostic utility for FTLD. Moreover, our novel computational approach can be used in future work to model various neurodegenerative disorders with mixed proteinopathy within the human brain connectome.

From single-neuron dynamics to higher-order circuit motifs in control and pathological brain networks.

The convergence of advanced single-cell in vivo functional imaging techniques, computational modelling tools and graph-based network analytics has heralded new opportunities to study single-cell dynamics across large-scale networks, providing novel insights into principles of brain communication and pointing towards potential new strategies for treating neurological disorders. A major recent finding has been the identification of unusually richly connected hub cells that have capacity to synchronize networks and may also be critical in network dysfunction. While hub neurons are traditionally defined by measures that consider solely the number and strength of connections, novel higher-order graph analytics now enables the mining of massive networks for repeating subgraph patterns called motifs. As an illustration of the power offered by higher-order analysis of neuronal networks, we highlight how recent methodological advances uncovered a new functional cell type, the superhub, that is predicted to play a major role in regulating network dynamics. Finally, we discuss open questions that will be critical for assessing the importance of higher-order cellular-scale network analytics in understanding brain function in health and disease.

Genetic architecture of inter-specific and -generic grass hybrids by network analysis on multi-omics data.

BACKGROUND: Understanding the mechanisms underlining forage production and its biomass nutritive quality at the omics level is crucial for boosting the output of high-quality dry matter per unit of land. Despite the advent of multiple omics integration for the study of biological systems in major crops, investigations on forage species are still scarce. RESULTS: Our results identified substantial changes in gene co-expression and metabolite-metabolite network topologies as a result of genetic perturbation by hybridizing L. perenne with another species within the genus (L. multiflorum) relative to across genera (F. pratensis). However, conserved hub genes and hub metabolomic features were detected between pedigree classes, some of which were highly heritable and displayed one or more significant edges with agronomic traits in a weighted omics-phenotype network. In spite of tagging relevant biological molecules as, for example, the light-induced rice 1 (LIR1), hub features were not necessarily better explanatory variables for omics-assisted prediction than features stochastically sampled and all available regressors. CONCLUSIONS: The utilization of computational techniques for the reconstruction of co-expression networks facilitates the identification of key omic features that serve as central nodes and demonstrate correlation with the manifestation of observed traits. Our results also indicate a robust association between early multi-omic traits measured in a greenhouse setting and phenotypic traits evaluated under field conditions.

Co-evolving dynamics and topology in a coupled oscillator model of resting brain function.

Dynamic models of ongoing BOLD fMRI brain dynamics and models of communication strategies have been two important approaches to understanding how brain network structure constrains function. However, dynamic models have yet to widely incorporate one of the most important insights from communication models: the brain may not use all of its connections in the same way or at the same time. Here we present a variation of a phase delayed Kuramoto coupled oscillator model that dynamically limits communication between nodes on each time step. An active subgraph of the empirically derived anatomical brain network is chosen in accordance with the local dynamic state on every time step, thus coupling dynamics and network structure in a novel way. We analyze this model with respect to its fit to empirical time-averaged functional connectivity, finding that, with the addition of only one parameter, it significantly outperforms standard Kuramoto models with phase delays. We also perform analyses on the novel time series of active edges it produces, demonstrating a slowly evolving topology moving through intermittent episodes of integration and segregation. We hope to demonstrate that the exploration of novel modeling mechanisms and the investigation of dynamics of networks in addition to dynamics on networks may advance our understanding of the relationship between brain structure and function.

Data science in unveiling COVID-19 pathogenesis and diagnosis: evolutionary origin to drug repurposing.

MOTIVATION: The outbreak of novel severe acute respiratory syndrome coronavirus (SARS-CoV-2, also known as COVID-19) in Wuhan has attracted worldwide attention. SARS-CoV-2 causes severe inflammation, which can be fatal. Consequently, there has been a massive and rapid growth in research aimed at throwing light on the mechanisms of infection and the progression of the disease. With regard to this data science is playing a pivotal role in in silico analysis to gain insights into SARS-CoV-2 and the outbreak of COVID-19 in order to forecast, diagnose and come up with a drug to tackle the virus. The availability of large multiomics, radiological, bio-molecular and medical datasets requires the development of novel exploratory and predictive models, or the customisation of existing ones in order to fit the current problem. The high number of approaches generates the need for surveys to guide data scientists and medical practitioners in selecting the right tools to manage their clinical data. RESULTS: Focusing on data science methodologies, we conduct a detailed study on the state-of-the-art of works tackling the current pandemic scenario. We consider various current COVID-19 data analytic domains such as phylogenetic analysis, SARS-CoV-2 genome identification, protein structure prediction, host-viral protein interactomics, clinical imaging, epidemiological research and drug discovery. We highlight data types and instances, their generation pipelines and the data science models currently in use. The current study should give a detailed sketch of the road map towards handling COVID-19 like situations by leveraging data science experts in choosing the right tools. We also summarise our review focusing on prime challenges and possible future research directions. CONTACT: hguzzi@unicz.it, sroy01@cus.ac.in.

Two pathways in vocabulary development: Large-scale differences in noun and verb semantic structure.

In adults, nouns and verbs have varied and multilevel semantic interrelationships. In children, evidence suggests that nouns and verbs also have semantic interrelationships, though the timing of the emergence of these relationships and their precise impact on later noun and verb learning are not clear. In this work, we ask whether noun and verb semantic knowledge in 16-30-month-old children tend to be semantically isolated from one another or semantically interacting from the onset of vocabulary development. Early word learning patterns were quantified using network science. We measured the semantic network structure for nouns and verbs in 3,804 16-30-month-old children at several levels of granularity using a large, open dataset of vocabulary checklist data. In a cross-sectional approach in Experiment 1, early nouns and verbs exhibited stronger network relationships with other nouns and verbs than expected across multiple network levels. Using a longitudinal approach in Experiment 2, we examined patterns of normative vocabulary development over time. Initial noun and verb learning was supported by strong semantic connections to other nouns, whereas later-learned words exhibited strong connections to verbs. Overall, these two experiments suggest that nouns and verbs demonstrate early semantic interactions and that these interactions impact later word learning. Early verb and noun learning is affected by the emergence of noun and verb semantic networks during early lexical development.

Discovering new pathways toward integration between health and sustainable development goals with natural language processing and network science.

BACKGROUND: Research on health and sustainable development is growing at a pace such that conventional literature review methods appear increasingly unable to synthesize all relevant evidence. This paper employs a novel combination of natural language processing (NLP) and network science techniques to address this problem and to answer two questions: (1) how is health thematically interconnected with the Sustainable Development Goals (SDGs) in global science? (2) What specific themes have emerged in research at the intersection between SDG 3 ("Good health and well-being") and other sustainability goals? METHODS: After a descriptive analysis of the integration between SDGs in twenty years of global science (2001-2020) as indexed by dimensions.ai, we analyze abstracts of articles that are simultaneously relevant to SDG 3 and at least one other SDG (N = 27,928). We use the top2vec algorithm to discover topics in this corpus and measure semantic closeness between these topics. We then use network science methods to describe the network of substantive relationships between the topics and identify 'zipper themes', actionable domains of research and policy to co-advance health and other sustainability goals simultaneously. RESULTS: We observe a clear increase in scientific research integrating SDG 3 and other SDGs since 2001, both in absolute and relative terms, especially on topics relevant to interconnections between health and SDGs 2 ("Zero hunger"), 4 ("Quality education"), and 11 ("Sustainable cities and communities"). We distill a network of 197 topics from literature on health and sustainable development, with 19 distinct network communities - areas of growing integration with potential to further bridge health and sustainability science and policy. Literature focused explicitly on the SDGs is highly central in this network, while topical overlaps between SDG 3 and the environmental SDGs (12-15) are under-developed. CONCLUSION: Our analysis demonstrates the feasibility and promise of NLP and network science for synthesizing large amounts of health-related scientific literature and for suggesting novel research and policy domains to co-advance multiple SDGs. Many of the 'zipper themes' identified by our method resonate with the One Health perspective that human, animal, and plant health are closely interdependent. This and similar perspectives will help meet the challenge of 'rewiring' sustainability research to co-advance goals in health and sustainability.