Causal Network Research Articles

Broadcasters, receivers, functional groups of metabolites, and the link to heart failure by revealing metabolomic network connectivity.

Blood-based small molecule metabolites offer easy accessibility and hold significant potential for insights into health processes, the impact of lifestyle, and genetic variation on disease, enabling precise risk prevention. In a prospective study with records of heart failure (HF) incidence, we present metabolite profiling data from individuals without HF at baseline. We uncovered the interconnectivity of metabolites using data-driven and causal networks augmented with polygenic factors. Exploring the networks, we identified metabolite broadcasters, receivers, mediators, and subnetworks corresponding to functional classes of metabolites, and provided insights into the link between metabolomic architecture and regulation in health. We incorporated the network structure into the identification of metabolites associated with HF to control the effect of confounding metabolites. We identified metabolites associated with higher and lower risk of HF incidence, such as glycine, ureidopropionic and glycocholic acids, and LPC 18:2. These associations were not confounded by the other metabolites due to uncovering the connectivity among metabolites and adjusting each association for the confounding metabolites. Examples of our findings include the direct influence of asparagine on glycine, both of which were inversely associated with HF. These two metabolites were influenced by polygenic factors and only essential amino acids, which are not synthesized in the human body and are obtained directly from the diet. Metabolites may play a critical role in linking genetic background and lifestyle factors to HF incidence. Revealing the underlying connectivity of metabolites associated with HF strengthens the findings and facilitates studying complex conditions like HF.

Hybrid approach to modeling labor productivity factors: Synthesis of randomized controlled experiments and causal Bayesian networks

Hybrid approach to modeling labor productivity factors: Synthesis of randomized controlled experiments and causal Bayesian networks

A causal counterfactual graph neural network for arising-from-chair abnormality detection in parkinsonians

The arising-from-chair task assessment is a key aspect of the evaluation of movement disorders in Parkinson's disease (PD). However, common scale-based clinical assessment methods are highly subjective and dependent on the neurologist's expertise. Alternate automated methods for arising-from-chair assessment can be established based on quantitative susceptibility mapping (QSM) images with multiple-instance learning. However, performance stability for such methods can be typically undermined by the presence of irrelevant or spuriously-relevant features that mask the intrinsic causal features. Therefore, we propose a QSM-based arising-from-chair assessment method using a causal graph-neural-network framework, where counterfactual and debiasing strategies are developed and integrated into this framework for capturing causal features. Specifically, the counterfactual strategy is proposed to suppress irrelevant features caused by background noise, by producing incorrect predictions when dropping causal parts. The debiasing strategy is proposed to suppress spuriously relevant features caused by the sampling bias and it comprises a resampling guidance scheme for selecting stable instances and a causal invariance constraint for improving stability under various interferences. The results of extensive experiments demonstrated the superiority of the proposed method in detecting arising-from-chair abnormalities. Its clinical feasibility was further confirmed by the coincidence between the selected causal features and those reported in earlier medical studies. Additionally, the proposed method was extensible for another motion task of leg agility. Overall, this study provides a potential tool for automated arising-from-chair assessment in PD patients, and also introduces causal counterfactual thinking in medical image analysis. Our source code is publicly available at https://github.com/SJTUBME-QianLab/CFGNN-PDarising.

A Causal Net approach to Relativistic Quantum Mechanics and Gravitation

In this paper we discuss a causal network model to describe quantum mechanics and gravittation, where space–time is built solely from point events and connecting probabilities. A causal net provides a representation which combines the quantum complementary features of both partticles and waves as each vertex on the causal net represents a possible point event or particle observation. Simultaneity on the causal net is defined by hyperplanes of equivalent proper time. The causal net model when constructed in Minkowksi space–time is shown to lead to a formulation for relativistic quantum mechanics including the Dirac equation. In a curved Riemann space–time the causal paths of the causal net are geodesics and in the local Lorentz frame the net probabilities and the Dirac formalism are preserved. The variation of space–time density of events in the causal paths modifies the metric and provides a space–time curvature leading to the Hilbert action associated with general relativity. Consideration of the Schwarzchild metric shows that in classical limit the perturbation in the density of possible events is proportional to the Newtonian gravitational potential.

Local neuronal sleep after stroke: The role of cortical bistability in brain reorganization

BackgroundAcute cerebral ischemia triggers a number of cellular mechanisms not only leading to excitotoxic cell death but also to enhanced neuroplasticity, facilitating neuronal reorganization and functional recovery. ObjectiveTransferring these cellular mechanisms to neurophysiological correlates adaptable to patients is crucial to promote recovery post-stroke. The combination of TMS and EEG constitutes a promising readout of neuronal network activity in stroke patients. MethodsWe used the combination of TMS and EEG to investigate the development of local signal processing and global network alterations in 40 stroke patients with motor deficits alongside neural reorganization from the acute to the chronic phase. ResultsWe show that the TMS-EEG response reflects information about reorganization and signal alterations associated with persistent motor deficits throughout the entire post-stroke period. In the early post-stroke phase and in a subgroup of patients with severe motor deficits, TMS applied to the lesioned motor cortex evoked a sleep-like slow wave response associated with a cortical off-period, a manifestation of cortical bistability, as well as a rapid disruption of the TMS-induced formation of causal network effects. Mechanistically, these phenomena were linked to lesions affecting ascending activating brainstem fibers. Of note, slow waves invariably vanished in the chronic phase, but were highly indicative of a poor functional outcome. ConclusionIn summary, we found evidence that transient effects of sleep-like slow waves and cortical bistability within ipsilesional M1 resulting in excessive inhibition may interfere with functional reorganization, leading to a less favorable functional outcome post-stroke, pointing to a new therapeutic target to improve recovery of function.

Long-Term Prediction on Graph Data With Causal Network Construction

Long-Term Prediction on Graph Data With Causal Network Construction

Turkey’s Trust in the USA: Causes of the Criticised Alliance Member’s Approach

The article deals with Turkey's trust in the USA as its most important ally in NATO. Semi-structured interviews with Turkish academics and international relations experts during field research identified three main areas of Turkish mistrust in the USA – the Cyprus question, USA support for the PYD/YPG in Syria, and USA intervention in Turkish politics. The research results presented in the causal network show that the main cause of Turkish mistrust towards the USA is the factors leading to the phenomenon of fear of abandonment. That causes Turkey's increased need for independence from strategic partners and the subsequent increase in the application of a balance policy. The study concludes that one of the main reasons for Turkey's current attitude towards NATO is the need to ensure its security, and this need stems from Turkey's mistrust of the USA.

Medical-informed machine learning: integrating prior knowledge into medical decision systems

BackgroundClinical medicine offers a promising arena for applying Machine Learning (ML) models. However, despite numerous studies employing ML in medical data analysis, only a fraction have impacted clinical care. This article underscores the importance of utilising ML in medical data analysis, recognising that ML alone may not adequately capture the full complexity of clinical data, thereby advocating for the integration of medical domain knowledge in ML.MethodsThe study conducts a comprehensive review of prior efforts in integrating medical knowledge into ML and maps these integration strategies onto the phases of the ML pipeline, encompassing data pre-processing, feature engineering, model training, and output evaluation. The study further explores the significance and impact of such integration through a case study on diabetes prediction. Here, clinical knowledge, encompassing rules, causal networks, intervals, and formulas, is integrated at each stage of the ML pipeline, resulting in a spectrum of integrated models.ResultsThe findings highlight the benefits of integration in terms of accuracy, interpretability, data efficiency, and adherence to clinical guidelines. In several cases, integrated models outperformed purely data-driven approaches, underscoring the potential for domain knowledge to enhance ML models through improved generalisation. In other cases, the integration was instrumental in enhancing model interpretability and ensuring conformity with established clinical guidelines. Notably, knowledge integration also proved effective in maintaining performance under limited data scenarios.ConclusionsBy illustrating various integration strategies through a clinical case study, this work provides guidance to inspire and facilitate future integration efforts. Furthermore, the study identifies the need to refine domain knowledge representation and fine-tune its contribution to the ML model as the two main challenges to integration and aims to stimulate further research in this direction.

Comparing attitudinal structures between political orientations: A network analysis of climate change attitudes

Research into climate change attitudes consistently and across countries finds ideologically and worldview-determined differences in threat perceptions and policy endorsements. To further our understanding of these ideological differences, the current study explores the underlying structure of climate attitudes across right- and left-oriented individuals. Based on survey data from a representative sample from Denmark (N = 1365) we deployed the Causal Attitude Network model to formalize attitudes as networks of interacting attitude elements. We compare the networks of different ideological groups and relate the observed patterns to previous findings and theories within the environmental and political psychology literatures. Overall, the two networks were found to be characterized by many similarities, for example, in global connectivity and patterns of node strength. Yet, the results also revealed differences in the most central nodes of right and left networks, as well as theoretically interesting differences in the predictors of important nodes. We discuss the implications of the findings for communication and engagement efforts.

The genetic architecture of biological age in nine human organ systems.

Investigating the genetic underpinnings of human aging is essential for unraveling the etiology of and developing actionable therapies for chronic diseases. Here, we characterize the genetic architecture of the biological age gap (BAG; the difference between machine learning-predicted age and chronological age) across nine human organ systems in 377,028 participants of European ancestry from the UK Biobank. The BAGs were computed using cross-validated support vector machines, incorporating imaging, physical traits and physiological measures. We identify 393 genomic loci-BAG pairs (P < 5 × 10-8) linked to the brain, eye, cardiovascular, hepatic, immune, metabolic, musculoskeletal, pulmonary and renal systems. Genetic variants associated with the nine BAGs are predominantly specific to the respective organ system (organ specificity) while exerting pleiotropic links with other organ systems (interorgan cross-talk). We find that genetic correlation between the nine BAGs mirrors their phenotypic correlation. Further, a multiorgan causal network established from two-sample Mendelian randomization and latent causal variance models revealed potential causality between chronic diseases (for example, Alzheimer's disease and diabetes), modifiable lifestyle factors (for example, sleep duration and body weight) and multiple BAGs. Our results illustrate the potential for improving human organ health via a multiorgan network, including lifestyle interventions and drug repurposing strategies.

Early Warning of Systemic Risk in Commodity Markets Based on Transfer Entropy Networks: Evidence from China.

This study aims to employ a causal network model based on transfer entropy for the early warning of systemic risk in commodity markets. We analyzed the dynamic causal relationships of prices for 25 commodities related to China (including futures and spot prices of energy, industrial metals, precious metals, and agricultural products), validating the effect of the causal network structure among commodity markets on systemic risk. Our research results identified commodities and categories playing significant roles, revealing that industry and precious metal markets possess stronger market information transmission capabilities, with price fluctuations impacting a broader range and with greater force on other commodity markets. Under the influence of different types of crisis events, such as economic crises and the Russia-Ukraine conflict, the causal network structure among commodity markets exhibited distinct characteristics. The results of the effect of external shocks to the causal network structure of commodity markets on the entropy of systemic risk suggest that network structure indicators can warn of systemic risk. This article can assist investors and policymakers in managing systemic risk to avoid unexpected losses.

Multilayer networks for measuring interconnectedness among global stock markets through the lens of trading volume-price relationship

Using daily data spanning from 5 January 2004 to 22 November 2022, we quantify the spillover effects between 42 global stock markets. Specifically, combining causal structure learning and Elastic-Net-VAR methods, we innovatively construct multilayer causal networks based on volume-price relationship. Then, we analyze the network characteristics of multilayer spillover networks from system and market levels. Our findings indicate that there is heterogeneity in risk spillovers of price and volume networks, highlighting how trading volume spillover network play an important role in the risk contagion. Furthermore, multilayer interconnected networks confirm the risk spillovers between volume and price, and it exhibits significant differences compared to single-layer network. In addition, at system-level, each network layer shows unique network structures and dynamic evolution characteristics. At market-level, global stock markets play different roles in emitting or receiving shocks through various transmission channels. Our study emphasizes the importance of intra- and inter-layer risk propagation in multilayer networks based on volume and price, and has significant implications for developing investment strategies and global portfolio risk management.

The subcortical brain regions influence the cortical areas during resting-state: an fMRI study.

Numerous modes or patterns of neural activity can be seen in the brain of individuals during the resting state. However, those functions do not persist long, and they are continuously altering in the brain. We have hypothesized that the brain activations during the resting state should themselves be responsible for this alteration of the activities. Using the resting-state fMRI data of 63 healthy young individuals, we estimated the causality effects of each resting-state activation map on all other networks. The resting-state networks were identified, their causality effects on the other components were extracted, the networks with the top 20% of the causality were chosen, and the networks which were under the influence of those causal networks were also identified. Our results showed that the influence of each activation component over other components is different. The brain areas which showed the highest causality coefficients were subcortical regions, such as the brain stem, thalamus, and amygdala. On the other hand, nearly all the areas which were mostly under the causal effects were cortical regions. In summary, our results suggest that subcortical brain areas exert a higher influence on cortical regions during the resting state, which could help in a better understanding the dynamic nature of brain functions.

Processes and principles for producing credible climate change attribution messages: lessons from Australia and New Zealand

Extreme event attribution (EEA) information is increasingly in demand from climate services. EEA messages can: raise awareness about the effect climate change has already imposed, inform climate change liability conversations, and be combined with climate projections to inform adaptation. However, due to limitations in observations, models and methods, there are barriers towards operationalising EEA in practice. Operational services will need EEA to be done transparently and using preset formats. Here we review recent experience and practice in EEA in Australia and New Zealand with a view to inform the design of an EEA component of climate services. We present a flow chart of the processes involved, noting particular care is needed on the trigger, event definition, and climate model evaluation, with effective stage gates. We also promote the use of tailored causal network diagrams as a standard tool to inform an EEA study and communicate results, with particular care needed for messages on events with lower confidence or complex sets of influences, including tropical cyclones and extratropical cyclones. We suggest that extending EEA to impact attribution is essential for making EEA messages salient but requires an uplift in forming interdisciplinary teams and in granular exposure and vulnerability datasets and is likely to raise new interdisciplinary methodological questions. Finally, we suggest communication of EEA messages can learn more from its origins in medical epidemiology.

Causal prior-embedded physics-informed neural networks and a case study on metformin transport in porous media

This study introduces a novel approach to transport modelling by integrating experimentally derived causal priors into neural networks. We illustrate this paradigm using a case study of metformin, a ubiquitous pharmaceutical emerging pollutant, and its transport behaviour in sandy media. Specifically, data from metformin's sandy column transport experiment was used to estimate unobservable parameters through a physics-based model Hydrus-1D, followed by a data augmentation to produce a more comprehensive dataset. A causal graph incorporating key variables was constructed, aiding in identifying impactful variables and estimating their causal dynamics or “causal prior.” The causal priors extracted from the augmented dataset included underexplored system parameters such as the type-1 sorption fraction F, first-order reaction rate coefficient α, and transport system scale. Their moderate impact on the transport process has been quantitatively evaluated (normalized causal effect 0.0423, -0.1447 and -0.0351, respectively) with adequate confounders considered for the first time. The prior was later embedded into multilayer neural networks via two methods: causal weight initialization and causal prior regularization. Based on the results from AutoML hyperparameter tuning experiments, using two embedding methods simultaneously emerged as a more advantageous practice since our proposed causal weight initialization technique can enhance model stability, particularly when used in conjunction with causal prior regularization. amongst those experiments utilizing both techniques, the R-squared values peaked at 0.881. This study demonstrates a balanced approach between expert knowledge and data-driven methods, providing enhanced interpretability in black-box models such as neural networks for environmental modelling.

Changing effects of external forcing on Atlantic–Pacific interactions

Abstract. Recent studies have highlighted the increasingly dominant role of external forcing in driving Atlantic and Pacific Ocean variability during the second half of the 20th century. This paper provides insights into the underlying mechanisms driving interactions between modes of variability over the two basins. We define a set of possible drivers of these interactions and apply causal discovery to reanalysis data, two ensembles of pacemaker simulations where sea surface temperatures in either the tropical Pacific or the North Atlantic are nudged to observations, and a pre-industrial control run. We also utilize large-ensemble means of historical simulations from the Coupled Model Intercomparison Project Phase 6 (CMIP6) to quantify the effect of external forcing and improve the understanding of its impact. A causal analysis of the historical time series between 1950 and 2014 identifies a regime switch in the interactions between major modes of Atlantic and Pacific climate variability in both reanalysis and pacemaker simulations. A sliding window causal analysis reveals a decaying El Niño–Southern Oscillation (ENSO) effect on the Atlantic as the North Atlantic fluctuates towards an anomalously warm state. The causal networks also demonstrate that external forcing contributed to strengthening the Atlantic's negative-sign effect on ENSO since the mid-1980s, where warming tropical Atlantic sea surface temperatures induce a La Niña-like cooling in the equatorial Pacific during the following season through an intensification of the Pacific Walker circulation. The strengthening of this effect is not detected when the historical external forcing signal is removed in the Pacific pacemaker ensemble. The analysis of the pre-industrial control run supports the notion that the Atlantic and Pacific modes of natural climate variability exert contrasting impacts on each other even in the absence of anthropogenic forcing. The interactions are shown to be modulated by the (multi)decadal states of temperature anomalies of both basins with stronger connections when these states are “out of phase”. We show that causal discovery can detect previously documented connections and provides important potential for a deeper understanding of the mechanisms driving changes in regional and global climate variability.

The Genetic Architecture of Biological Age in Nine Human Organ Systems.

Understanding the genetic basis of biological aging in multi-organ systems is vital for elucidating age-related disease mechanisms and identifying therapeutic interventions. This study characterized the genetic architecture of the biological age gap (BAG) across nine human organ systems in 377,028 individuals of European ancestry from the UK Biobank. We discovered 393 genomic loci-BAG pairs (P-value<5×10-8) linked to the brain, eye, cardiovascular, hepatic, immune, metabolic, musculoskeletal, pulmonary, and renal systems. We observed BAG-organ specificity and inter-organ connections. Genetic variants associated with the nine BAGs are predominantly specific to the respective organ system while exerting pleiotropic effects on traits linked to multiple organ systems. A gene-drug-disease network confirmed the involvement of the metabolic BAG-associated genes in drugs targeting various metabolic disorders. Genetic correlation analyses supported Cheverud's Conjecture1 - the genetic correlation between BAGs mirrors their phenotypic correlation. A causal network revealed potential causal effects linking chronic diseases (e.g., Alzheimer's disease), body weight, and sleep duration to the BAG of multiple organ systems. Our findings shed light on promising therapeutic interventions to enhance human organ health within a complex multi-organ network, including lifestyle modifications and potential drug repositioning strategies for treating chronic diseases. All results are publicly available at https://labs-laboratory.com/medicine.

CAT: A causal graph attention network for trimming heterophilic graphs

The local attention-guided message passing mechanism (LAMP) adopted in graph attention networks (GATs) can adaptively learn the importance of neighboring nodes and perform local aggregation better, thus demonstrating a stronger discrimination ability. However, existing GATs suffer from significant discrimination ability degradations in heterophilic graphs. The reason is that a high proportion of dissimilar neighbors can weaken the self-attention of the central node, resulting in the central node deviating from its similar nodes in the representation space. This type of influence caused by neighboring nodes is referred to as Distraction Effect (DE) in this paper. To estimate and weaken the DE induced by neighboring nodes, we propose a Causal graph Attention network for Trimming heterophilic graphs (CAT). To estimate the DE, since DE is generated through two paths, we adopt the total effect as the metric for estimating DE; To weaken the DE, we identify the neighbors with the highest DE (we call them Distraction Neighbors) and remove them. We adopt three representative GATs as the base model within the proposed CAT framework and conduct experiments on seven heterophilic datasets of three different sizes. Comparative experiments show that CAT can improve the node classification accuracies of all base GAT models. Ablation experiments and visualization further validate the enhanced discrimination ability of CATs. In addition, CAT is a plug-and-play framework and can be introduced to any LAMP-driven GAT because it learns a trimmed graph in the attention-learning stage, instead of modifying the model architecture or globally searching for new neighbors.

The impact of variable ordering on Bayesian network structure learning

Causal Bayesian Networks (CBNs) provide an important tool for reasoning under uncertainty with potential application to many complex causal systems. Structure learning algorithms that can tell us something about the causal structure of these systems are becoming increasingly important. In the literature, the validity of these algorithms is often tested for sensitivity over varying sample sizes, hyper-parameters, and occasionally objective functions, but the effect of the order in which the variables are read from data is rarely quantified. We show that many commonly-used algorithms, both established and state-of-the-art, are more sensitive to variable ordering than these other factors when learning CBNs from discrete variables. This effect is strongest in hill-climbing and its variants where we explain how it arises, but extends to hybrid, and to a lesser-extent, constraint-based algorithms. Because the variable ordering is arbitrary, any significant effect it has on learnt graph accuracy is concerning, and raises questions about the validity of both many older and more recent results produced by these algorithms in practical applications and their rankings in performance evaluations.

FABP4 Is an Indispensable Factor for Regulating Cellular Metabolic Functions of the Human Retinal Choroid.

The purpose of the current study was to elucidate the physiological roles of intraocularly present fatty acid-binding protein 4 (FABP4). Using four representative intraocular tissue-derived cell types, including human non-pigmented ciliary epithelium (HNPCE) cells, retinoblastoma (RB) cells, adult retinal pigment epithelial19 (ARPE19) cells and human ocular choroidal fibroblast (HOCF) cells, the intraocular origins of FABP4 were determined by qPCR analysis, and the intracellular functions of FABP4 were investigated by seahorse cellular metabolic measurements and RNA sequencing analysis using a specific inhibitor for FABP4, BMS309403. Among these four different cell types, FABP4 was exclusively expressed in HOCF cells. In HOCF cells, both mitochondrial and glycolytic functions were significantly decreased to trace levels by BMS309403 in a dose-dependent manner. In the RNA sequencing analysis, 67 substantially up-regulated and 94 significantly down-regulated differentially expressed genes (DEGs) were identified in HOCF cells treated with BMS309403 and those not treated with BMS309403. The results of Gene Ontology enrichment analysis and ingenuity pathway analysis (IPA) revealed that the DEGs were most likely involved in G-alpha (i) signaling, cAMP-response element-binding protein (CREB) signaling in neurons, the S100 family signaling pathway, visual phototransduction and adrenergic receptor signaling. Furthermore, upstream analysis using IPA suggested that NKX2-1 (thyroid transcription factor1), HOXA10 (homeobox A10), GATA2 (gata2 protein), and CCAAT enhancer-binding protein A (CEBPA) were upstream regulators and that NKX homeobox-1 (NKX2-1), SFRP1 (Secreted frizzled-related protein 1) and TREM2 (triggering receptor expressed on myeloid cells 2) were causal network master regulators. The findings in this study suggest that intraocularly present FABP4 originates from the ocular choroid and may be a critical regulator for the cellular homeostasis of non-adipocyte HOCF cells.