Immune Gene Networks from Lung Cancer Patients Treated with Immune Checkpoint Inhibitors.

The association between immune checkpoint inhibitors (ICIs) and immune gene networks in squamous lung cancer (LUSC) and lung adenocarcinoma (LUAD) was studied. Immune gene networks were constructed using RNA-seq data from the gene expression omnibus (GEO) database. Datasets with more than 10 samples of normal control and tumor tissues were selected; of these, GSE87340, GSE120622, and GSE111907 were suitable for analysis. Gene set enrichment for pathway analysis was performed. For immune gene network construction, 998 unique immune genes were selected from 21 pathways in the Kyoto Encyclopedia of Genes and Genomes (KEGG). Gene function annotation was performed based on the KEGG, Gene Ontology, and Reactome databases. Tumor tissues showed decreased coagulation, hematopoiesis, and innate immune pathways, whereas complement- and coagulation-related genes were prominent in the tumor immune gene network. The average numbers of neighbors, clustering coefficients, network diameters, path lengths, densities, and heterogeneities were highest for normal tissue, followed by LUAD and LUSC. Decreased coagulation genes, which were prominent in tumor immune networks, imply functional attenuation. LUAD was deviated from normal tissue, based on network parameters. Tumor tissues showed decreased immune function, and the deviation of LUSC from normal tissue might explain LUSC's better therapeutic response to ICI treatment.

High-density electroencephalographic functional networks in genetic generalized epilepsy: Preserved whole-brain topology hides local reorganization.

OBJECTIVE: Genetic generalized epilepsy (GGE) accounts for approximately 20% of adult epilepsy cases and is considered a disorder of large brain networks, involving both hemispheres. Most studies have not shown any difference in functional whole-brain network topology when compared to healthy controls. Our objective was to examine whether this preserved global network topology could hide local reorganizations that balance out at the global network level. METHODS: We recorded high-density electroencephalograms from 20 patients and 20 controls, and reconstructed the activity of 118 regions. We computed functional connectivity in windows free of interictal epileptiform discharges in broad, delta, theta, alpha, and beta frequency bands, characterized the network topology, and used the Hub Disruption Index (HDI) to quantify the topological reorganization. We examined the generalizability of our results by reproducing a 25-electrode clinical system. RESULTS: Our study did not reveal any significant change in whole-brain network topology among GGE patients. However, the HDI was significantly different between patients and controls in all frequency bands except alpha (p < .01, false discovery rate [FDR] corrected, d < -1), and accompanied by an increase in connectivity in the prefrontal regions and default mode network. This reorganization suggests that regions that are important in transferring the information in controls were less so in patients. Inversely, the crucial regions in patients are less so in controls. These findings were also found in delta and theta frequency bands when using 25 electrodes (p < .001, FDR corrected, d < -1). SIGNIFICANCE: In GGE patients, the overall network topology is similar to that of healthy controls but presents a balanced local topological reorganization. This reorganization causes the prefrontal areas and default mode network to be more integrated and segregated, which may explain executive impairment associated with GGE. Additionally, the reorganization distinguishes patients from controls even when using 25 electrodes, suggesting its potential use as a diagnostic tool.

MEM-FET: Essential protein prediction using membership feature and machine learning approach.

Proteins are played key roles in different functionalities in our daily life. All functional roles of a protein are a bit enhanced in interaction compared to individuals. Identification of essential proteins of an organism is a time consume and costly task during observation in the wet lab. The results of observation in wet lab always ensure high reliability and accuracy in the biological ground. Essential protein prediction using computational approaches is an alternative choice in research. It proves its significance rapidly in day-to-day life as well as reduces the experimental cost of wet lab effectively. Existing computational methods were implemented using Protein interaction networks (PPIN), Sequence, Gene Expression Dataset (GED), Gene Ontology (GO), Orthologous groups, and Subcellular localized datasets. Machine learning has diverse categories of features that enable to model and predict essential macromolecules of understudied organisms. A novel methodology MEM-FET (membership feature) is predicted based on features, that is, edge clustering coefficient, Average clustering coefficient, subcellular localization, and Gene Ontology within a compartment of common neighbors. The accuracy (ACC) values of the predicted true positive (TP) essential proteins are 0.79, 0.74, 0.78, and 0.71 for YHQ, YMIPS, YDIP, and YMBD datasets. An enriched set of essential proteins are also predicted using the MEM-FET algorithm. Ensemble ML also validated the proposed model with an accuracy of 60%. It has been predicted that MEM-FET algorithms outperform other existing algorithms with an ACC value of 80% for the yeast dataset.

Thinner inner retinal layers are associated with lower cognitive performance, lower brain volume, and altered white matter network structure-The Maastricht Study.

INTRODUCTION: The retina may provide non-invasive, scalable biomarkers for monitoring cerebral neurodegeneration. METHODS: We used cross-sectional data from The Maastricht study (n = 3436; mean age 59.3 years; 48% men; and 21% with type 2 diabetes [the latter oversampled by design]). We evaluated associations of retinal nerve fiber layer, ganglion cell layer, and inner plexiform layer thicknesses with cognitive performance and magnetic resonance imaging indices (global grey and white matter volume, hippocampal volume, whole brain node degree, global efficiency, clustering coefficient, and local efficiency). RESULTS: After adjustment, lower thicknesses of most inner retinal layers were significantly associated with worse cognitive performance, lower grey and white matter volume, lower hippocampal volume, and worse brain white matter network structure assessed from lower whole brain node degree, lower global efficiency, higher clustering coefficient, and higher local efficiency. DISCUSSION: The retina may provide biomarkers that are informative of cerebral neurodegenerative changes in the pathobiology of dementia.

Effectiveness of a COVID-19 contact tracing app in a simulation model with indirect and informal contact tracing.

During the COVID-19 pandemic, contact tracing was used to identify individuals who had been in contact with a confirmed case so that these contacted individuals could be tested and quarantined to prevent further spread of the SARS-CoV-2 virus. Many countries developed mobile apps to find these contacted individuals faster. We evaluate the epidemiological effectiveness of the Dutch app CoronaMelder, where we measure effectiveness as the reduction of the reproduction number R. To this end, we use a simulation model of SARS-CoV-2 spread and contact tracing, informed by data collected during the study period (December 2020 - March 2021) in the Netherlands. We show that the tracing app caused a clear but small reduction of the reproduction number, and the magnitude of the effect was found to be robust in sensitivity analyses. The app could have been more effective if more people had used it, and if notification of contacts could have been done directly by the user and thus reducing the time intervals between symptom onset and reporting of contacts. The model has two innovative aspects: i) it accounts for the clustered nature of social networks and ii) cases can alert their contacts informally without involvement of health authorities or the tracing app.

Delving into gene-set multiplex networks facilitated by a k-nearest neighbor-based measure of similarity.

Gene sets are functional units for living cells. Previously, limited studies investigated the complex relations among gene sets, but documents about their altering patterns across biological conditions still need to be prepared. In this study, we adopted and modified a classical k-nearest neighbor-based association function to detect inter-gene-set similarities. Based on this method, we built multiplex networks of gene sets for the first time; these networks contain layers of gene sets corresponding to different populations of cells. The context-based multiplex networks can capture meaningful biological variation and have considerable differences from knowledge-based networks of gene sets built on Jaccard similarity, as demonstrated in this study. Furthermore, at the scale of individual gene sets, the structural coefficients of gene sets (multiplex PageRank centrality, clustering coefficient, and participation coefficient) disclose the diversity of gene sets from the perspective of structural properties and make it easier to identify unique gene sets. In gene set enrichment analysis (GSEA), each gene set is treated independently, and its contextual and relational attributes are ignored. The structural coefficients of gene sets can supplement GSEA with information about the overall picture of gene sets, promoting the constructive reorganization of the enriched terms and helping researchers better prioritize and select gene sets.

Unique Brain Network Identification Number for Parkinson's and Healthy Individuals Using Structural MRI.

We propose a novel algorithm called Unique Brain Network Identification Number (UBNIN) for encoding the brain networks of individual subjects. To realize this objective, we employed structural MRI on 180 Parkinson's disease (PD) patients and 70 healthy controls (HC) from the National Institute of Mental Health and Neurosciences, India. We parcellated each subject's brain volume and constructed an individual adjacency matrix using the correlation between the gray matter volumes of every pair of regions. The unique code is derived from values representing connections for every node (i), weighted by a factor of 2-(i-1). The numerical representation (UBNIN) was observed to be distinct for each individual brain network, which may also be applied to other neuroimaging modalities. UBNIN ranges observed for PD were 15,360 to 17,768,936,615,460,608, and HC ranges were 12,288 to 17,733,751,438,064,640. This model may be implemented as a neural signature of a person's unique brain connectivity, thereby making it useful for brainprinting applications. Additionally, we segregated the above datasets into five age cohorts: A: ≤32 years (n1 = 4, n2 = 5), B: 33-42 years (n1 = 18, n2 = 14), C: 43-52 years (n1 = 42, n2 = 23), D: 53-62 years (n1 = 69, n2 = 22), and E: ≥63 years (n1 = 46, n2 = 6), where n1 and n2 are the number of individuals in PD and HC, respectively, to study the variation in network topology over age. Sparsity was adopted as the threshold estimate to binarize each age-based correlation matrix. Connectivity metrics were obtained using Brain Connectivity toolbox (Version 2019-03-03)-based MATLAB (R2020a) functions. For each age cohort, a decreasing trend was observed in the mean clustering coefficient with increasing sparsity. Significantly different clustering coefficients were noted in PD between age-cohort B and C (sparsity: 0.63, 0.66), C and E (sparsity: 0.66, 0.69), and in HC between E and B (sparsity: 0.75 and above 0.81), E and C (sparsity above 0.78), E and D (sparsity above 0.84), and C and D (sparsity: 0.9). Our findings suggest network connectivity patterns change with age, indicating network disruption may be due to the underlying neuropathology. Varying clustering coefficients for different cohorts indicate that information transfer between neighboring nodes changes with age. This provides evidence of age-related brain shrinkage and network degeneration. We also discuss limitations and provide an open-access link to software codes and a help file for the entire study.

LazyFox: fast and parallelized overlapping community detection in large graphs.

The detection of communities in graph datasets provides insight about a graph's underlying structure and is an important tool for various domains such as social sciences, marketing, traffic forecast, and drug discovery. While most existing algorithms provide fast approaches for community detection, their results usually contain strictly separated communities. However, most datasets would semantically allow for or even require overlapping communities that can only be determined at much higher computational cost. We build on an efficient algorithm, Fox, that detects such overlapping communities. Fox measures the closeness of a node to a community by approximating the count of triangles which that node forms with that community. We propose LazyFox, a multi-threaded adaptation of the Fox algorithm, which provides even faster detection without an impact on community quality. This allows for the analyses of significantly larger and more complex datasets. LazyFox enables overlapping community detection on complex graph datasets with millions of nodes and billions of edges in days instead of weeks. As part of this work, LazyFox's implementation was published and is available as a tool under an MIT licence at https://github.com/TimGarrels/LazyFox.

Clustering drives cooperation on reputation networks, all else fixed.

Reputation-based cooperation on social networks offers a causal mechanism between graph properties and social trust. Using a simple model, this paper demonstrates the underlying mechanism in a way that is accessible to scientists not specializing in networks or mathematics. The paper shows that when the size and degree of the network is fixed (i.e. all graphs have the same number of agents, who all have the same number of connections), it is the clustering coefficient that drives differences in how cooperative social networks are.

MM-CCNB: Essential protein prediction using MAX-MIN strategies and compartment of common neighboring approach.

BACKGROUND AND OBJECTIVE: Proteins are indispensable for the flow of the life of living organisms. Protein pairs in interaction exhibit more functional activities than individuals. These activities have been considered an essential measure in predicting their essentiality. Neighborhood approaches have been used frequently in the prediction of essentiality scores. All paired neighbors of the essential proteins are nominated for the suitable candidate seeds for prediction. Still now Jaccard's coefficient is limited to predicting functions, homologous groups, sequence analysis, etc. It really motivate us to predict essential proteins efficiently using different computational approaches. METHODS: In our work, we proposed modified Jaccard's coefficient to predict essential proteins. We have proposed a novel methodology for predicting essential proteins using MAX-MIN strategies and modified Jaccard's coefficient approach. RESULTS: The performance of our proposed methodology has been analyzed for Saccharomyces cerevisiae datasets with an accuracy of more than 80%. It has been observed that the proposed algorithm is outperforms with an accuracy of 0.78, 0.74, 0.79, and 0.862 for YDIP, YMIPS, YHQ, and YMBD datasets respectivly. CONCLUSIONS: There are several computational approaches in the existing state-of-art model of essential protein prediction. It has been noted that our predicted methodology outperforms other existing models viz. different centralities, local interaction density combined with protein complexes, modified monkey algorithm and ortho_sim_loc methods.

The thalamic clustering coefficient moderates the vigor-sleep quality relationship.

Sleep disorders affect more than one-quarter of the world's population, resulting in reduced daytime productivity, impaired immune function, and an increased risk of cardiovascular disease. It is important to identify the physiological and psychological factors related to sleep for the prevention and treatment of sleep disorders. In this study, we correlated measurements of emotional state, sleep quality, and some brain neural activity parameters to better understand the brain and psychological factors related to sleep. Resting-state functional magnetic resonance imaging (rs-fMRI) of 116 healthy undergraduates were analyzed using graph theory to assess regional topological characteristics. Among these, the left thalamic cluster coefficient proved to be the ablest to reflect the characteristics of the sleep neural graph index. The Profile of Mood States (POMS) was used to measure vigor, and the Pittsburgh Sleep Quality Index (PSQI) to assess sleep quality. The results showed that the left thalamic clustering coefficient was negatively correlated with sleep quality and vigor. Further, the left thalamic clustering coefficient moderated the relationship between vigor and sleep quality. When the left thalamic clustering coefficient was very low, there was a significant positive correlation between vigor and sleep quality. However, when the left thalamic clustering coefficient was high, the correlation between vigor and sleep quality became insignificant. The relationship between vigor and sleep quality is heterogeneous. Analyzing the function of the left thalamic neural network could help understand the variation in the relationship between vigor and sleep quality in different populations. Such observations may help in the development of personalized interventions for sleep disorders.

[Dynamic analysis of epileptic causal brain networks based on directional transfer function].

Epilepsy is a neurological disease with disordered brain network connectivity. It is important to analyze the brain network mechanism of epileptic seizure from the perspective of directed functional connectivity. In this paper, causal brain networks were constructed for different sub-bands of epileptic electroencephalogram (EEG) signals in interictal, preictal and ictal phases by directional transfer function method, and the information transmission pathway and dynamic change process of brain network under different conditions were analyzed. Finally, the dynamic changes of characteristic attributes of brain networks with different rhythms were analyzed. The results show that the topology of brain network changes from stochastic network to rule network during the three stage and the node connections of the whole brain network show a trend of gradual decline. The number of pathway connections between internal nodes of frontal, temporal and occipital regions increase. There are a lot of hub nodes with information outflow in the lesion region. The global efficiency in ictal stage of α, ß and γ waves are significantly higher than in the interictal and the preictal stage. The clustering coefficients in preictal stage are higher than in the ictal stage and the clustering coefficients in ictal stage are higher than in the interictal stage. The clustering coefficients of frontal, temporal and parietal lobes are significantly increased. The results of this study indicate that the topological structure and characteristic properties of epileptic causal brain network can reflect the dynamic process of epileptic seizures. In the future, this study has important research value in the localization of epileptic focus and prediction of epileptic seizure.

Financial resilience of insurance network during Covid-19 pandemic.

We provide a novel approach for analysing the financial resilience of the insurance sector during coronavirus pandemic. To this end, we build temporal directed and weighted networks where the weights on the arcs take into account the tail dependence between couple of firms. To assess the resilience of the network, we provide a new global indicator, aimed at capturing the impact on the clustering coefficient of a shock affecting in turn each firm and diffusing in the network via shortest paths. A local measure of resilience is also provided by quantifying the contribution of each firm to the global indicator. In this way, we are able to detect most critical firms in the system. A numerical application has been developed in order to test the proposed approach. The results show that the proposed resilience measure appears able to detect main periods of financial crises. The first wave of COVID-19 pandemic results as a extreme phenomenon in the market and the lowest resilience is associated to the period in which COVID-19 has been declared pandemic.

Functional network characteristics based on EEG of patients in acute ischemic stroke: A pilot study.

BACKGROUND: Ischemic stroke is a common type of stroke associated with reorganization of functional network of the brain. OBJECTIVE: This pilot study aimed to investigate the characteristics of functional brain networks based on EEG in patients with acute ischemic stroke. METHODS: Seven patients with ischemic stroke within 72 hours of onset and seven healthy controls were enrolled in the study. Dynamic EEG monitoring and clinical information were repeatedly collected within 72 hours (T1), on the 5th day (T2), and on the 7th day (T3) of stroke onset. A directed transfer function was employed to construct functional brain connection patterns. Graph theoretical analysis was performed to evaluate the characteristics of functional brain networks. RESULTS: First, we found that the brain networks of ischemic stroke patients were quite different from the healthy controls. The clustering coefficient (0.001 < Threshold < 0.2) in Delta, Theta, and Alpha bands for the patients were significantly lower (P < 0.01) and the shortest path length in all bands (0.001 < Threshold < 0.2) for the patients were significantly longer (P < 0.01). Moreover, the peaks of the shortest path length for the patients seemed to be higher in all bands with larger thresholds. Secondly, the brain networks for the patients showed a characterized time-variation pattern. The clustering coefficient (0.001 < Threshold < 0.2) of T1 was higher than that of T2 in alpha band (P < 0.01). The shortest path length (0.001 < Threshold < 0.2) of T3 was shorter than that of T2 (P < 0.01) in all bands, and the peak of T3 was numerically higher than that of T2 in all bands with narrower thresholds. CONCLUSION: Functional brain networks in patients with acute ischemic stroke showed impaired global functional integration and decreased efficiency of information transmission compared with healthy subjects. The shortening of the shortest path length during the recovery indicates neural plasticity and reorganization.

Modeling the early transmission of COVID-19 in New York and San Francisco using a pairwise network model.

Classical epidemiological models assume mass action. However, this assumption is violated when interactions are not random. With the recent COVID-19 pandemic, and resulting shelter in place social distancing directives, mass action models must be modified to account for limited social interactions. In this paper we apply a pairwise network model with moment closure to study the early transmission of COVID-19 in New York and San Francisco and to investigate the factors determining the severity and duration of outbreak in these two cities. In particular, we consider the role of population density, transmission rates and social distancing on the disease dynamics and outcomes. Sensitivity analysis shows that there is a strongly negative correlation between the clustering coefficient in the pairwise model and the basic reproduction number and the effective reproduction number. The shelter in place policy makes the clustering coefficient increase thereby reducing the basic reproduction number and the effective reproduction number. By switching population densities in New York and San Francisco we demonstrate how the outbreak would progress if New York had the same density as San Francisco and vice-versa. The results underscore the crucial role that population density has in the epidemic outcomes. We also show that under the assumption of no further changes in policy or transmission dynamics not lifting the shelter in place policy would have little effect on final outbreak size in New York, but would reduce the final size in San Francisco by 97%.

Structural brain network correlations with amyloid burden in elderly individuals at risk of Alzheimer's disease.

Alzheimer's disease (AD) has a long preclinical phase during which beta-amyloid accumulates in the brain without cognitive impairment. However, the pattern of brain network alterations in this early stage of the disease remains to be clarified. In this study we examined the relationships between regional brain network indices and beta-amyloid deposits. Twenty-four elderly subjects with the APOE4 allele underwent both a 1.5-Tesla magnetic resonance imaging (MRI) scan and a positron emission tomography (PET) scan using [18F]Florbetapir. We computed network metrics such as the degree, betweenness centrality, and clustering coefficient, and examined the relationships between the beta-amyloid accumulation and these regional brain network connectivity metrics. We found a significant positive correlation between the global standardized uptake value ratio (SUVR) of [18F]Florbetapir and the betweenness centrality in the left parietal region. However, there were no significant correlations between the SUVR score and other network indices or the regional gray matter volume. Our data suggest a relationship between the beta-amyloid accumulation and the regional brain network connectivity in subjects at risk of AD. The brain connectome may provide an adjunct biomarker for the early detection of AD.

Dynamic analysis of epileptic causal brain networks based on directional transfer function / 生物医学工程学杂志

Epilepsy is a neurological disease with disordered brain network connectivity. It is important to analyze the brain network mechanism of epileptic seizure from the perspective of directed functional connectivity. In this paper, causal brain networks were constructed for different sub-bands of epileptic electroencephalogram (EEG) signals in interictal, preictal and ictal phases by directional transfer function method, and the information transmission pathway and dynamic change process of brain network under different conditions were analyzed. Finally, the dynamic changes of characteristic attributes of brain networks with different rhythms were analyzed. The results show that the topology of brain network changes from stochastic network to rule network during the three stage and the node connections of the whole brain network show a trend of gradual decline. The number of pathway connections between internal nodes of frontal, temporal and occipital regions increase. There are a lot of hub nodes with information outflow in the lesion region. The global efficiency in ictal stage of α, β and γ waves are significantly higher than in the interictal and the preictal stage. The clustering coefficients in preictal stage are higher than in the ictal stage and the clustering coefficients in ictal stage are higher than in the interictal stage. The clustering coefficients of frontal, temporal and parietal lobes are significantly increased. The results of this study indicate that the topological structure and characteristic properties of epileptic causal brain network can reflect the dynamic process of epileptic seizures. In the future, this study has important research value in the localization of epileptic focus and prediction of epileptic seizure.

Corrigendum: Overlapping Structures Detection in Protein-Protein Interaction Networks Using Community Detection Algorithm Based on Neighbor Clustering Coefficient.

[This corrects the article DOI: 10.3389/fgene.2021.689515.].

Association between brain structural network efficiency at term-equivalent age and early development of cerebral palsy in very preterm infants.

Very preterm infants (born at less than 32 weeks gestational age) are at high risk for serious motor impairments, including cerebral palsy (CP). The brain network changes that antecede the early development of CP in infants are not well characterized, and a better understanding may suggest new strategies for risk-stratification at term, which could lead to earlier access to therapies. Graph theoretical methods applied to diffusion MRI-derived brain connectomes may help quantify the organization and information transfer capacity of the preterm brain with greater nuance than overt structural or regional microstructural changes. Our aim was to shed light on the pathophysiology of early CP development, before the occurrence of early intervention therapies and other environmental confounders, to help identify the best early biomarkers of CP risk in VPT infants. In a cohort of 395 very preterm infants, we extracted cortical morphometrics and brain volumes from structural MRI and also applied graph theoretical methods to diffusion MRI connectomes, both acquired at term-equivalent age. Metrics from graph network analysis, especially global efficiency, strength values of the major sensorimotor tracts, and local efficiency of the motor nodes and novel non-motor regions were strongly inversely related to early CP diagnosis. These measures remained significantly associated with CP after correction for common risk factors of motor development, suggesting that metrics of brain network efficiency at term may be sensitive biomarkers for early CP detection. We demonstrate for the first time that in VPT infants, early CP diagnosis is anteceded by decreased brain network segregation in numerous nodes, including motor regions commonly-associated with CP and also novel regions that may partially explain the high rate of cognitive impairments concomitant with CP diagnosis. These advanced MRI biomarkers may help identify the highest risk infants by term-equivalent age, facilitating earlier interventions that are informed by early pathophysiological changes.

Diffusion Tensor Imaging Changes Do Not Affect Long-Term Neurodevelopment following Early Erythropoietin among Extremely Preterm Infants in the Preterm Erythropoietin Neuroprotection Trial.

We aimed to evaluate diffusion tensor imaging (DTI) in infants born extremely preterm, to determine the effect of erythropoietin (Epo) on DTI, and to correlate DTI with neurodevelopmental outcomes at 2 years of age for infants in the Preterm Erythropoietin Neuroprotection (PENUT) Trial. Infants who underwent MRI with DTI at 36 weeks postmenstrual age were included. Neurodevelopmental outcomes were evaluated by Bayley Scales of Infant and Toddler Development (BSID-III). Generalized linear models were used to assess the association between DTI parameters and treatment group, and then with neurodevelopmental outcomes. A total of 101 placebo- and 93 Epo-treated infants underwent MRI. DTI white matter mean diffusivity (MD) was lower in placebo- compared to Epo-treated infants in the cingulate and occipital regions, and occipital white matter fractional isotropy (FA) was lower in infants born at 24-25 weeks vs. 26-27 weeks. These values were not associated with lower BSID-III scores. Certain decreases in clustering coefficients tended to have lower BSID-III scores. Consistent with the PENUT Trial findings, there was no effect on long-term neurodevelopment in Epo-treated infants even in the presence of microstructural changes identified by DTI.