Application of physiological network mapping in the prediction of survival in critically ill patients with acute liver failure.

Reduced functional connectivity of physiological systems is associated with poor prognosis in critically ill patients. However, physiological network analysis is not commonly used in clinical practice and awaits quantitative evidence. Acute liver failure (ALF) is associated with multiorgan failure and mortality. Prognostication in ALF is highly important for clinical management but is currently dependent on models that do not consider the interaction between organ systems. This study aims to examine whether physiological network analysis can predict survival in patients with ALF. Data from 640 adult patients admitted to the ICU for paracetamol-induced ALF were extracted from the MIMIC-III database. Parenclitic network analysis was performed on the routine biomarkers using 28-day survivors as reference population and network clusters were identified for survivors and non-survivors using k-clique percolation method. Network analysis showed that liver function biomarkers were more clustered in survivors than in non-survivors. Arterial pH was also found to cluster with serum creatinine and bicarbonate in survivors compared with non-survivors, where it clustered with respiratory nodes indicating physiologically distinctive compensatory mechanism. Deviation along the pH-bicarbonate and pH-creatinine axes significantly predicts mortality independent of current prognostic indicators. These results demonstrate that network analysis can provide pathophysiologic insight and predict survival in critically ill patients with ALF.

Spatial scales of COVID-19 transmission in Mexico.

During outbreaks of emerging infectious diseases, internationally connected cities often experience large and early outbreaks, while rural regions follow after some delay. This hierarchical structure of disease spread is influenced primarily by the multiscale structure of human mobility. However, during the COVID-19 epidemic, public health responses typically did not take into consideration the explicit spatial structure of human mobility when designing nonpharmaceutical interventions (NPIs). NPIs were applied primarily at national or regional scales. Here, we use weekly anonymized and aggregated human mobility data and spatially highly resolved data on COVID-19 cases at the municipality level in Mexico to investigate how behavioral changes in response to the pandemic have altered the spatial scales of transmission and interventions during its first wave (March-June 2020). We find that the epidemic dynamics in Mexico were initially driven by exports of COVID-19 cases from Mexico State and Mexico City, where early outbreaks occurred. The mobility network shifted after the implementation of interventions in late March 2020, and the mobility network communities became more disjointed while epidemics in these communities became increasingly synchronized. Our results provide dynamic insights into how to use network science and epidemiological modeling to inform the spatial scale at which interventions are most impactful in mitigating the spread of COVID-19 and infectious diseases in general.

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.

Machine learning applications in preventive healthcare: A systematic literature review on predictive analytics of disease comorbidity from multiple perspectives.

Artificial intelligence is constantly revolutionizing biomedical research and healthcare management. Disease comorbidity is a major threat to the quality of life for susceptible groups, especially middle-aged and elderly patients. The presence of multiple chronic diseases makes precision diagnosis challenging to realize and imposes a heavy burden on the healthcare system and economy. Given an enormous amount of accumulated health data, machine learning techniques show their capability in handling this puzzle. The present study conducts a review to uncover current research efforts in applying these methods to understanding comorbidity mechanisms and making clinical predictions considering these complex patterns. A descriptive metadata analysis of 791 unique publications aims to capture the overall research progression between January 2012 and June 2023. To delve into comorbidity-focused research, 61 of these scientific papers are systematically assessed. Four predictive analytics of tasks are detected: disease comorbidity data extraction, clustering, network, and risk prediction. It is observed that some machine learning-driven applications address inherent data deficiencies in healthcare datasets and provide a model interpretation that identifies significant risk factors of comorbidity development. Based on insights, both technical and practical, gained from relevant literature, this study intends to guide future interests in comorbidity research and draw conclusions about chronic disease prevention and diagnosis with managerial implications.

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.

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.

Using network science to provide insights into the structure of event knowledge.

The structure of event knowledge plays a critical role in prediction, reconstruction of memory for personal events, construction of possible future events, action, language usage, and social interactions. Despite numerous theoretical proposals such as scripts, schemas, and stories, the highly variable and rich nature of events and event knowledge have been formidable barriers to characterizing the structure of event knowledge in memory. We used network science to provide insights into the temporal structure of common events. Based on participants' production and ordering of the activities that make up events, we established empirical profiles for 80 common events to characterize the temporal structure of activities. We used the event networks to investigate multiple issues regarding the variability in the richness and complexity of people's knowledge of common events, including: the temporal structure of events; event prototypes that might emerge from learning across many experiential instances and be expressed by people; the degree to which scenes (communities) are present in various events; the degree to which people believe certain activities are central to an event; how centrality might be distributed across an event's activities; and similarities among events in terms of their content and their temporal structure. Thus, we provide novel insights into human event knowledge, and describe 18 predictions for future human studies.

Emergent scale-free networks.

Many complex systems-from the Internet to social, biological, and communication networks-are thought to exhibit scale-free structure. However, prevailing explanations require that networks grow over time, an assumption that fails in some real-world settings. Here, we explain how scale-free structure can emerge without growth through network self-organization. Beginning with an arbitrary network, we allow connections to detach from random nodes and then reconnect under a mixture of preferential and random attachment. While the numbers of nodes and edges remain fixed, the degree distribution evolves toward a power-law with an exponent γ = 1 + 1 p that depends only on the proportion p of preferential (rather than random) attachment. Applying our model to several real networks, we infer p directly from data and predict the relationship between network size and degree heterogeneity. Together, these results establish how scale-free structure can arise in networks of constant size and density, with broad implications for the structure and function of complex systems.

Enhancing visual communication through representation learning.

Introduction: This research aims to address the challenges in model construction for the Extended Mind for the Design of the Human Environment. Specifically, we employ the ResNet-50, LSTM, and Object Tracking Algorithms approaches to achieve collaborative construction of high-quality virtual assets, image optimization, and intelligent agents, providing users with a virtual universe experience in the context of visual communication. Methods: Firstly, we utilize ResNet-50 as a convolutional neural network model for generating virtual assets, including objects, characters, and environments. By training and fine-tuning ResNet-50, we can generate virtual elements with high realism and rich diversity. Next, we use LSTM (Long Short-Term Memory) for image processing and analysis of the generated virtual assets. LSTM can capture contextual information in image sequences and extract/improve the details and appearance of the images. By applying LSTM, we further enhance the quality and realism of the generated virtual assets. Finally, we adopt Object Tracking Algorithms to track and analyze the movement and behavior of virtual entities within the virtual environment. Object Tracking Algorithms enable us to accurately track the positions and trajectories of objects, characters, and other elements, allowing for realistic interactions and dynamic responses. Results and discussion: By integrating the technologies of ResNet-50, LSTM, and Object Tracking Algorithms, we can generate realistic virtual assets, optimize image details, track and analyze virtual entities, and train intelligent agents, providing users with a more immersive and interactive visual communication-driven metaverse experience. These innovative solutions have important applications in the Extended Mind for the Design of the Human Environment, enabling the creation of more realistic and interactive virtual worlds.

Autocatalysis, Autopoiesis, and the Opportunity Cost of Individuality.

Ever since Varela and Maturana proposed the concept of autopoiesis as the minimal requirement for life, there has been a focus on cellular systems that erect topological boundaries to separate themselves from their surrounding environment. Here, we reconsider whether the existence of such a spatial boundary is strictly necessary for self-producing entities. This work presents a novel computational model of a minimal autopoietic system inspired by dendrites and molecular dynamic simulations in three-dimensional space. A series of simulation experiments where the metabolic pathways of a particular autocatalytic set are successively inhibited until autocatalytic entities that could be considered autopoietic are produced. These entities maintain their distinctness in an environment containing multiple identical instances of the entities without the existence of a topological boundary. This gives rise to the concept of a metabolic boundary which manifests as emergent self-selection criteria for the processes of self-production without any need for unique identifiers. However, the adoption of such a boundary comes at a cost, as these autopoietic entities are less suited to their simulated environment than their autocatalytic counterparts. Finally, this work showcases a generalized metabolism-centered approach to the study of autopoiesis that can be applied to both physical and abstract systems alike.

Mapping the Memory Structure of High-Knowledge Students: A Longitudinal Semantic Network Analysis.

Standard learning assessments like multiple-choice questions measure what students know but not how their knowledge is organized. Recent advances in cognitive network science provide quantitative tools for modeling the structure of semantic memory, revealing key learning mechanisms. In two studies, we examined the semantic memory networks of undergraduate students enrolled in an introductory psychology course. In Study 1, we administered a cumulative multiple-choice test of psychology knowledge, the Intro Psych Test, at the end of the course. To estimate semantic memory networks, we administered two verbal fluency tasks: domain-specific fluency (naming psychology concepts) and domain-general fluency (naming animals). Based on their performance on the Intro Psych Test, we categorized students into a high-knowledge or low-knowledge group, and compared their semantic memory networks. Study 1 (N = 213) found that the high-knowledge group had semantic memory networks that were more clustered, with shorter distances between concepts-across both the domain-specific (psychology) and domain-general (animal) categories-compared to the low-knowledge group. In Study 2 (N = 145), we replicated and extended these findings in a longitudinal study, collecting data near the start and end of the semester. In addition to replicating Study 1, we found the semantic memory networks of high-knowledge students became more interconnected over time, across both domain-general and domain-specific categories. These findings suggest that successful learners show a distinct semantic memory organization-characterized by high connectivity and short path distances between concepts-highlighting the utility of cognitive network science for studying variation in student learning.

Distinct Network Patterns Emerge from Cartesian and XOR Epistasis Models: A Comparative Network Science Analysis.

Background: Epistasis, the phenomenon where the effect of one gene (or variant) is masked or modified by one or more other genes, can significantly contribute to the observed phenotypic variance of complex traits. To date, it has been generally assumed that genetic interactions can be detected using a Cartesian, or multiplicative, interaction model commonly utilized in standard regression approaches. However, a recent study investigating epistasis in obesity-related traits in rats and mice has identified potential limitations of the Cartesian model, revealing that it only detects some of the genetic interactions occurring in these systems. By applying an alternative approach, the exclusive-or (XOR) model, the researchers detected a greater number of epistatic interactions and identified more biologically relevant ontological terms associated with the interacting loci. This suggests that the XOR model may provide a more comprehensive understanding of epistasis in these species and phenotypes. To further explore these findings and determine if different interaction models also make up distinct epistatic networks, we leverage network science to provide a more comprehensive view into the genetic interactions underlying BMI in this system. Results: Our comparative analysis of networks derived from Cartesian and XOR interaction models in rats (Rattus norvegicus) uncovers distinct topological characteristics for each model-derived network. Notably, we discover that networks based on the XOR model exhibit an enhanced sensitivity to epistatic interactions. This sensitivity enables the identification of network communities, revealing novel trait-related biological functions through enrichment analysis. Furthermore, we identify triangle network motifs in the XOR epistatic network, suggestive of higher-order epistasis, based on the topology of lower-order epistasis. Conclusions: These findings highlight the XOR model's ability to uncover meaningful biological associations as well as higher-order epistasis from lower-order epistatic networks. Additionally, our results demonstrate that network approaches not only enhance epistasis detection capabilities but also provide more nuanced understandings of genetic architectures underlying complex traits. The identification of community structures and motifs within these distinct networks, especially in XOR, points to the potential for network science to aid in the discovery of novel genetic pathways and regulatory networks. Such insights are important for advancing our understanding of phenotype-genotype relationships.

Multilayer biological networks to upscale marine research to global change-smart management and sustainable resource use.

Human activities are having a massive negative impact on biodiversity and ecological processes worldwide. The rate and magnitude of ecological transformations induced by climate change, habitat destruction, overexploitation and pollution are now so substantial that a sixth mass extinction event is currently underway. The biodiversity crisis of the Anthropocene urges scientists to put forward a transformative vision to promote the conservation of biodiversity, and thus indirectly the preservation of ecosystem functions. Here, we identify pressing issues in global change biology research and propose an integrative framework based on multilayer biological networks as a tool to support conservation actions and marine risk assessments in multi-stressor scenarios. Multilayer networks can integrate different levels of environmental and biotic complexity, enabling us to combine information on molecular, physiological and behaviour responses, species interactions and biotic communities. The ultimate aim of this framework is to link human-induced environmental changes to species physiology, fitness, biogeography and ecosystem impacts across vast seascapes and time frames, to help guide solutions to address biodiversity loss and ecological tipping points. Further, we also define our current ability to adopt a widespread use of multilayer networks within ecology, evolution and conservation by providing examples of case-studies. We also assess which approaches are ready to be transferred and which ones require further development before use. We conclude that multilayer biological networks will be crucial to inform (using reliable multi-levels integrative indicators) stakeholders and support their decision-making concerning the sustainable use of resources and marine conservation.

[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.

A gray box framework that optimizes a white box logical model using a black box optimizer for simulating cellular responses to perturbations.

Predicting cellular responses to perturbations requires interpretable insights into molecular regulatory dynamics to perform reliable cell fate control, despite the confounding non-linearity of the underlying interactions. There is a growing interest in developing machine learning-based perturbation response prediction models to handle the non-linearity of perturbation data, but their interpretation in terms of molecular regulatory dynamics remains a challenge. Alternatively, for meaningful biological interpretation, logical network models such as Boolean networks are widely used in systems biology to represent intracellular molecular regulation. However, determining the appropriate regulatory logic of large-scale networks remains an obstacle due to the high-dimensional and discontinuous search space. To tackle these challenges, we present a scalable derivative-free optimizer trained by meta-reinforcement learning for Boolean network models. The logical network model optimized by the trained optimizer successfully predicts anti-cancer drug responses of cancer cell lines, while simultaneously providing insight into their underlying molecular regulatory mechanisms.

Functional network organization is locally atypical in children and adolescents with congenital heart disease.

Children and adolescents with congenital heart disease (CHD) frequently experience neurodevelopmental impairments that can impact academic performance, memory, attention, and behavioral function, ultimately affecting overall quality of life. This study aims to investigate the impact of CHD on functional brain network connectivity and cognitive function. Using resting-state fMRI data, we examined several network metrics across various brain regions utilizing weighted networks and binarized networks with both absolute and proportional thresholds. Regression models were fitted to patient neurocognitive exam scores using various metrics obtained from all three methods. Our results unveil significant differences in network connectivity patterns, particularly in temporal, occipital, and subcortical regions, across both weighted and binarized networks. Furthermore, we identified distinct correlations between network metrics and cognitive performance, suggesting potential compensatory mechanisms within specific brain regions.

Dynamic contact networks of residents of an urban jail in the era of SARS-CoV-2.

BACKGROUND: In custodial settings such as jails and prisons, infectious disease transmission is heightened by factors such as overcrowding and limited healthcare access. Specific features of social contact networks within these settings have not been sufficiently characterized, especially in the context of a large-scale respiratory infectious disease outbreak. The study aims to quantify contact network dynamics within the Fulton County Jail in Atlanta, Georgia. METHODS: Jail roster data were utilized to construct social contact networks. Rosters included resident details, cell locations, and demographic information. This analysis involved 6702 male residents over 140,901 person days. Network statistics, including degree, mixing, and dissolution (movement within and out of the jail) rates, were assessed. We compared outcomes for two distinct periods (January 2022 and April 2022) to understand potential responses in network structures during and after the SARS-CoV-2 Omicron variant peak. RESULTS: We found high cross-sectional network degree at both cell and block levels. While mean degree increased with age, older residents exhibited lower degree during the Omicron peak. Block-level networks demonstrated higher mean degrees than cell-level networks. Cumulative degree distributions increased from January to April, indicating heightened contacts after the outbreak. Assortative age mixing was strong, especially for younger residents. Dynamic network statistics illustrated increased degrees over time, emphasizing the potential for disease spread. CONCLUSIONS: Despite some reduction in network characteristics during the Omicron peak, the contact networks within the Fulton County Jail presented ideal conditions for infectious disease transmission. Age-specific mixing patterns suggested unintentional age segregation, potentially limiting disease spread to older residents. This study underscores the necessity for ongoing monitoring of contact networks in carceral settings and provides valuable insights for epidemic modeling and intervention strategies, including quarantine, depopulation, and vaccination, laying a foundation for understanding disease dynamics in such environments.Top of Form.

A spectral framework to map QTLs affecting joint differential networks of gene co-expression.

Studying the mechanisms underlying the genotype-phenotype association is crucial in genetics. Gene expression studies have deepened our understanding of the genotype → expression → phenotype mechanisms. However, traditional expression quantitative trait loci (eQTL) methods often overlook the critical role of gene co-expression networks in translating genotype into phenotype. This gap highlights the need for more powerful statistical methods to analyze genotype → network → phenotype mechanism. Here, we develop a network-based method, called snQTL, to map quantitative trait loci affecting gene co-expression networks. Our approach tests the association between genotypes and joint differential networks of gene co-expression via a tensor-based spectral statistics, thereby overcoming the ubiquitous multiple testing challenges in existing methods. We demonstrate the effectiveness of snQTL in the analysis of three-spined stickleback (Gasterosteus aculeatus) data. Compared to conventional methods, our method snQTL uncovers chromosomal regions affecting gene co-expression networks, including one strong candidate gene that would have been missed by traditional eQTL analyses. Our framework suggests the limitation of current approaches and offers a powerful network-based tool for functional loci discoveries.

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.