Linear non-Gaussian Acyclic Model Research Articles

Solving the puzzle of quality of life in cancer: integrating causal inference and machine learning for data-driven insights

BackgroundUnderstanding the determinants of global quality of life in cancer patients is crucial for improving their overall well-being. While correlations between various factors and quality of life have been established, the causal relationships remain largely unexplored. This study aimed to identify the causal factors influencing global quality of life in cancer patients and compare them with known correlative factors.MethodsWe conducted a retrospective analysis of European Organization for Research and Treatment of Cancer Quality of Life Questionnaire data, alongside demographic and disease-related features, collected from new cancer patients during their initial visit to an oncology outpatient clinic. Correlations with global quality of life were identified using univariate and multivariate regression analyses. Causal inference analysis was performed using two approaches. First, we employed the Dowhy Python library for causal analysis, incorporating prior information and manual characterization of an acyclic graph. Second, we utilized the Linear Non-Gaussian Acyclic Model (LiNGAM) machine learning algorithm from the Lingam Python library, which automatically generated an acyclic graph without prior information. The significance level was set at p < 0.05.ResultsMultivariate analysis of 469 new admissions revealed that disease stage, role functioning, emotional functioning, social functioning, fatigue, pain and diarrhea were linked with global quality of life. The most influential direct causal factors were emotional functioning, social functioning, and physical functioning, while the most influential indirect factors were physical functioning, emotional functioning, and fatigue. Additionally, the most prominent total causal factors were identified as type of cancer (diagnosis), cancer stage, and sex, with total causal effect ratios of -9.47, -4.67, and − 1.48, respectively. The LiNGAM algorithm identified type of cancer (diagnosis), nausea and vomiting and social functioning as significant, with total causal effect ratios of -9.47, -0.42, and 0.42, respectively.ConclusionsThis study identified that causal factors for global quality of life in new cancer patients are distinct from correlative factors. Understanding these causal relationships could provide valuable insights into the complex dynamics of quality of life in cancer patients and guide targeted interventions to improve their well-being.

A Bayesian incorporated linear non-Gaussian acyclic model for multiple directed graph estimation to study brain emotion circuit development in adolescence

Abstract Emotion perception is essential to affective and cognitive development which involves distributed brain circuits. Emotion identification skills emerge in infancy and continue to develop throughout childhood and adolescence. Understanding the development of the brain’s emotion circuitry may help us explain the emotional changes during adolescence. In this work, we aim to deepen our understanding of emotion-related functional connectivity (FC) from association to causation. We proposed a Bayesian incorporated linear non-Gaussian acyclic model (BiLiNGAM), which incorporated association model into the estimation pipeline. Simulation results indicated stable and accurate performance over various settings, especially when the sample size was small. We used fMRI data from the Philadelphia Neurodevelopmental Cohort (PNC) to validate the approach. It included 855 individuals aged 8–22 years who were divided into five different adolescent stages. Our network analysis revealed the development of emotion-related intra- and intermodular connectivity and pinpointed several emotion-related hubs. We further categorized the hubs into two types: in-hubs and out-hubs, as the center of receiving and distributing information, respectively. In addition, several unique developmental hub structures and group-specific patterns were discovered. Our findings help provide a directed FC template of brain network organization underlying emotion processing during adolescence.

Prediction and causal inference of hyperuricemia using gut microbiota.

Hyperuricemia (HUA) is a symptom of high blood uric acid (UA) levels, which causes disorders such as gout and renal urinary calculus. Prolonged HUA is often associated with hypertension, atherosclerosis, diabetes mellitus, and chronic kidney disease. Studies have shown that gut microbiota (GM) affect these chronic diseases. This study aimed to determine the relationship between HUA and GM. The microbiome of 224 men and 254 women aged 40years was analyzed through next-generation sequencing and machine learning. We obtained GM data through 16S rRNA-based sequencing of the fecal samples, finding that alpha-diversity by Shannon index was significantly low in the HUA group. Linear discriminant effect size analysis detected a high abundance of the genera Collinsella and Faecalibacterium in the HUA and non-HUA groups. Based on light gradient boosting machine learning, we propose that HUA can be predicted with high AUC using four clinical characteristics and the relative abundance of nine bacterial genera, including Collinsella and Dorea. In addition, analysis of causal relationships using a direct linear non-Gaussian acyclic model indicated a positive effect of the relative abundance of the genus Collinsella on blood UA levels. Our results suggest abundant Collinsella in the gut can increase blood UA levels.

Problematic social media use and psychological symptoms in adolescents.

This study examined time trends in significant child and adolescent psychological symptoms and explored the association of frequent and problematic social media use with these symptoms. Time trends in psychological symptoms were assessed using data from five waves of the international survey of Health Behavior in School-aged Children (HBSC), conducted between 2001 and 2018 (N = 1,036,869). The associations of frequent and problematic social media use with significant psychological symptoms were assessed by hierarchical multinomial logistic regression using data from 2001-2002 and the 2017-2018 survey waves. The direction of effect between social media use variables and psychological symptoms was explored using Linear Non-Gaussian Acyclic Models (LiNGAM). Prevalence of more severe psychological symptoms increased from 6.7% in 2001-2002 to 10.4% in the 2017-2018 survey waves. The increase was especially large among 15-year old and older girls: from 10.9 to 19.1%. The higher prevalence of more severe psychological symptoms in 2017-2018 compared with 2001-2002 was eliminated after adjusting the model for problematic social media use. LiNGAM analysis supported the direction of effect going from social media use and problematic social media use to psychological symptoms. The findings suggest that frequent and problematic use of social media contribute to the increasing trend of psychological symptoms in adolescents in recent years.

Determining causality in travel mode choice

This article presents one of the pioneering studies on causal modeling in travel mode choice decision-making using causal discovery algorithms. These models are a major advancement from conventional correlation-based techniques. We propose a novel methodology that combines causal discovery with structural equation modeling (SEM). This modeling approach overcomes some of the limitations of SEM by combining the strengths of both causal discovery and SEM. Causal discovery algorithms determine causal graphs from observational data and domain knowledge, and SEMs estimate direct causal effects and test the performance of causal discovery algorithms. In this study, we test four causal discovery algorithms: Peter-Clark (PC), Fast Causal Inference (FCI), Fast Greedy Equivalence Search (FGES), and Direct Linear Non-Gaussian Acyclic Models (DirectLiNGAM). The results show that DirectLiNGAM based SEM model best captures causality in mode choice behavior. It passes several goodness-of-fit tests, including Root Mean Square Error of Approximation (RMSEA) and Goodness-of-Fit Index (GFI), and it achieves the lowest Bayesian Information Criterion (BIC) value. The analyses are conducted on data collected from the 2017 National Household Travel Survey in the New York Metropolitan area.

Functional linear non-Gaussian acyclic model for causal discovery

Functional linear non-Gaussian acyclic model for causal discovery

Contemporaneous causality among office property prices of major Chinese cities with vector error correction modeling and directed acyclic graphs

PurposeThis study aims to investigate dynamic relations among office property price indices of 10 major cities in China for the years 2005–2021.Design/methodology/approachUsing monthly data, the authors adopt vector error correction modeling and the directed acyclic graph for the characterization of contemporaneous causality among the 10 indices.FindingsThe PC algorithm identifies the causal pattern, and the linear non-Gaussian acyclic model algorithm further determines the causal path from which we perform innovation accounting analysis. Sophisticated price dynamics are found in price adjustment processes following price shocks, which are generally dominated by the top tier of cities.Originality/valueThis suggests that policies on office property prices, in the long run, might need to be planned with particular attention paid to the top tier of cities.

Impact of gut microbiome on the renin-aldosterone system: Shika-machi Super Preventive Health Examination results.

The renin-angiotensin-aldosterone system (RAAS) is a regulatory mechanism of the endocrine system and is associated with various diseases, including hypertension and renal and cardiovascular diseases. The gut microbiota (GM) have been associated with various diseases, mainly in animal models. However, to our knowledge, no studies have examined the relationship between the RAAS and GM in humans. The present study aimed to assess the association between the systemic RAAS and GM genera and their causal relationships. The study participants were 377 members of the general population aged 40 years or older in Shika-machi, Japan. Plasma renin activity (PRA), plasma aldosterone concentration (PAC), aldosterone-renin ratio (ARR), and GM composition were analyzed using the 16S rRNA method. The participants were divided into high and low groups according to the PRA, PAC, and ARR values. U-tests, one-way analysis of covariance, and linear discriminant analysis of effect size were used to identify the important bacterial genera between the two groups, and binary classification modeling using Random Forest was used to calculate the importance of the features. The results showed that Blautia, Bacteroides, Akkermansia, and Bifidobacterium were associated with the RAAS parameters. Causal inference analysis using the linear non-Gaussian acyclic model revealed a causal effect of Blautia on PAC via SBP. These results strengthen the association between the systemic RAAS and GM in humans, and interventions targeting the GM may provide new preventive measures and treatments for hypertension and renal disease.

ParaLiNGAM: Parallel causal structure learning for linear non-Gaussian acyclic models

One of the key objectives in many fields in machine learning is to discover causal relationships among a set of variables from observational data. In linear non-Gaussian acyclic models (LiNGAM), it can be shown that the true underlying causal structure can be identified uniquely from merely observational data. The DirectLiNGAM algorithm is a well-known solution to learn the true causal structure in a high dimensional setting. DirectLiNGAM algorithm executes in a sequence of iterations and it performs a set of comparisons between pairs of variables in each iteration. Unfortunately, the runtime of this algorithm grows significantly as the number of variables increases. In this paper, we propose a parallel algorithm, called ParaLiNGAM, to learn casual structures based on DirectLiNGAM algorithm. We propose a threshold mechanism that can reduce the number of comparisons remarkably compared with the sequential solution. Moreover, in order to further reduce runtime, we employ a messaging mechanism between workers. We also present an implementation of ParaLiNGAM on GPU, considering hardware constraints. Experimental results on synthetic and real data show that our proposed solution outperforms DirectLiNGAM by a factor up to 4788X, and by a median of 2344X.

An integrated vector error correction and directed acyclic graph method for investigating contemporaneous causalities

This study introduces an integrated vector error correction and directed acyclic graph method for investigating contemporaneous causalities with application to regional scrap steel prices in east, north, south, central, northeast, and southwest China. We use daily data and combine the Peter and Clark (PC) and Linear NonGaussian Acyclic Model (LiNGAM) algorithms to discover contemporaneous causalities. The vector error correction model shows each of the six series is part of cointegration relationships, and prices of north and southwest regions do not respond to long-run equilibrium disturbances. The PC algorithm shows the causal patterns, and the LiNGAM algorithm discovers the causal paths that enable the analysis of innovation accounting. Based upon impulse responses, we sort out sophisticated dynamics among price adjustment processes following shocks, for which north and southwest regions dominate price adjustment processes compared to the other four regions. The proposed approach provides short-term and long-term pricing policies for scrap steel throughout China.

Application of quantum computing to a linear non-Gaussian acyclic model for novel medical knowledge discovery.

Recently, the utilization of real-world medical data collected from clinical sites has been attracting attention. Especially as the number of variables in real-world medical data increases, causal discovery becomes more and more effective. On the other hand, it is necessary to develop new causal discovery algorithms suitable for small data sets for situations where sample sizes are insufficient to detect reasonable causal relationships, such as rare diseases and emerging infectious diseases. This study aims to develop a new causal discovery algorithm suitable for a small number of real-world medical data using quantum computing, one of the emerging information technologies attracting attention for its application in machine learning. In this study, a new algorithm that applies the quantum kernel to a linear non-Gaussian acyclic model, one of the causal discovery algorithms, is developed. Experiments on several artificial data sets showed that the new algorithm proposed in this study was more accurate than existing methods with the Gaussian kernel under various conditions in the low-data regime. When the new algorithm was applied to real-world medical data, a case was confirmed in which the causal structure could be correctly estimated even when the amount of data was small, which was not possible with existing methods. Furthermore, the possibility of implementing the new algorithm on real quantum hardware was discussed. This study suggests that the new proposed algorithm using quantum computing might be a good choice among the causal discovery algorithms in the low-data regime for novel medical knowledge discovery.

Causal analysis of nitrogen oxides emissions process in coal-fired power plant with LiNGAM

Coal has been an important energy source worldwide; however, it is the largest source of nitrogen oxide (NOx) emissions because the amount of nitrogen in coal is larger than that of other fossil fuels. Precise control of NOx emissions is required in operations of coal-fired power plants from the viewpoint of air pollution control. Although theoretical analyses of NOx generation from a coal-fired power plant have been conducted, it is difficult to precisely predict NOx generation in an actual plant. NOx generation is affected by various factors, such as furnace design and operating conditions, and there are complicated relationships among them. Thus, it is necessary to identify important operating factors that affect NOx generation in actual coal-fired power plants. A linear non-Gaussian acyclic model (LiNGAM) is an exploratory causal analysis method that identifies a causal ordering of variables and their connection strengths without any prior knowledge of causal relationships among variables. In this study, we analyzed real operation data collected from a coal-fired power plant using LiNGAM to identify factors of NOx generation. The causal relationship between process variables and NOx generation was estimated by means of LiNGAM, and the connectional strengths of the variables on NOx generation were derived. The analysis results agreed with previous reports on NOx generation mechanisms, such as combustion air temperature, steam temperature on a specific side of the furnace, and air flow rate of forced draft fans. In addition, we found the steam flow rate and the furnace pressure as new candidate factors of NOx generation through causal analysis using LiNGAM, which heretofore has not been suggested. Our analysis result should contribute to reducing NOx emissions from coal-fired power plants in the future.

Impact of gut microbiome on serum IgG4 levels in the general population: Shika-machi super preventive health examination results.

Immunoglobulin G4 (IgG4) is a member of the human immunoglobulin G (IgG) subclass, a protein involved in immunity to pathogens and the body's resistance system. IgG4-related diseases (IgG4-RD) are intractable diseases in which IgG4 levels in the blood are elevated, causing inflammation in organs such as the liver, pancreas, and salivary glands. IgG4-RD are known to be more prevalent in males than in females, but the etiology remains to be elucidated. This study was conducted to investigate the relationship between gut microbiota (GM) and serum IgG4 levels in the general population. In this study, the relationship between IgG4 levels and GM evaluated in male and female groups of the general population using causal inference. The study included 191 men and 207 women aged 40 years or older from Shika-machi, Ishikawa. GM DNA was analyzed for the 16S rRNA gene sequence using next-generation sequencing. Participants were bifurcated into high and low IgG4 groups, depending on median serum IgG4 levels. ANCOVA, Tukey's HSD, linear discriminant analysis effect size, least absolute shrinkage and selection operator logistic regression model, and correlation analysis revealed that Anaerostipes, Lachnospiraceae, Megasphaera, and [Eubacterium] hallii group were associated with IgG4 levels in women, while Megasphaera, [Eubacterium] hallii group, Faecalibacterium, Ruminococcus.1, and Romboutsia were associated with IgG4 levels in men. Linear non-Gaussian acyclic model indicated three genera, Megasphaera, [Eubacterium] hallii group, and Anaerostipes, and showed a presumed causal association with IgG4 levels in women. This differential impact of the GM on IgG4 levels based on sex is a novel and intriguing finding.

Computational estimation of sediment symbiotic bacterial structures of seagrasses overgrowing downstream of onshore aquaculture

Coastal seagrass meadows are essential in blue carbon and aquatic ecosystem services. However, this ecosystem has suffered severe eutrophication and destruction due to the expansion of aquaculture. Therefore, methods for the flourishing of seagrass are still being explored. Here, data from 49 public coastal surveys on the distribution of seagrass and seaweed around the onshore aquaculture facilities are revalidated, and an exceptional area where the seagrass Zostera marina thrives was found near the shore downstream of the onshore aquaculture facility. To evaluate the characteristics of the sediment for growing seagrass, physicochemical properties and bacterial ecological evaluations of the sediment were conducted. Evaluation of chemical properties in seagrass sediments confirmed a significant increase in total carbon and a decrease in zinc content. Association analysis and linear discriminant analysis refined bacterial candidates specified in seagrass overgrown- and nonovergrown-sediment. Energy landscape analysis indicated that the symbiotic bacterial groups of seagrass sediment were strongly affected by the distance close to the seagrass-growing aquaculture facility despite their bacterial population appearing to fluctuate seasonally. The bacterial population there showed an apparent decrease in the pathogen candidates belonging to the order Flavobacteriales. Moreover, structure equation modeling and a linear non-Gaussian acyclic model based on the machine learning data estimated an optimal sediment symbiotic bacterial group candidate for seagrass growth as follows: the Lachnospiraceae and Ruminococcaceae families as gut-inhabitant bacteria, Rhodobacteraceae as photosynthetic bacteria, and Desulfobulbaceae as cable bacteria modulating oxygen or nitrate reduction and oxidation of sulfide. These observations confer a novel perspective on the sediment symbiotic bacterial structures critical for blue carbon and low-pathogenic marine ecosystems in aquaculture.

Causal Plot: Causal-Based Fault Diagnosis Method Based on Causal Analysis

Fault diagnosis is crucial for realizing safe process operation when a fault occurs. Multivariate statistical process control (MSPC) has widely been adopted for fault detection in real processes, and contribution plots based on MSPC are a well-known fault diagnosis method, but it does not always correctly diagnose the causes of faults. This study proposes a new fault diagnosis method based on the causality between process variables and a monitored index for fault detection, which is referred to as a causal plot. The proposed causal plot utilizes a linear non-Gaussian acyclic model (LiNGAM), which is a data-driven causal inference algorithm. LiNGAM estimates a causal structure only from data. In the proposed causal plot, the causality of a monitored index of fault detection methods, in addition to process variables, is estimated with LiNGAM when a fault is detected with the monitored index. The process variables having significant causal relationships with the monitored indexes are identified as causes of faults. In this study, the proposed causal plot was applied to fault diagnosis problems of a vinyl acetate monomer (VAM) manufacturing process. The application results showed that the proposed causal plot diagnosed appropriate causes of faults even when conventional contribution plots could not do the same. In addition, we discuss the effects of the presence of a recycle flow on fault diagnosis results based on the analysis result of the VAM process. The proposed causal plot contributes to realizing safe and efficient process operations.

Impact of gut microbiome on dyslipidemia in japanese adults: Assessment of the Shika-machi super preventive health examination results for causal inference.

Dyslipidemia (DL) is one of the most common lifestyle-related diseases. There are few reports showing the causal relationship between gut microbiota (GM) and DL. In the present study, we used a linear non-Gaussian acyclic model (LiNGAM) to evaluate the causal relationship between GM and DL. A total of 79 men and 82 women aged 40 years or older living in Shika-machi, Ishikawa Prefecture, Japan were included in the analysis, and their clinical information was investigated. DNA extracted from the GM was processed to sequence the 16S rRNA gene using next-generation sequencing. Participants were divided into four groups based on sex and lipid profile information. The results of one-way analysis of covariance, linear discriminant analysis effect size, and least absolute value reduction and selection operator logistic regression model indicated that several bacteria between men and women may be associated with DL. The LiNGAM showed a presumed causal relationship between different bacteria and lipid profiles in men and women. In men, Prevotella 9 and Bacteroides were shown to be potentially associated with changes in low- and high-density lipoprotein cholesterol levels. In women, the LiNGAM results showed two bacteria, Akkermansia and Escherichia/Shigella, had a presumptive causal relationship with lipid profiles. These results may provide a new sex-based strategy to reduce the risk of developing DL and to treat DL through the regulation of the intestinal environment using specific GM.

Causal Discovery in Linear Non-Gaussian Acyclic Model With Multiple Latent Confounders.

Causal discovery from observational data is a fundamental problem in science. Though the linear non-Gaussian acyclic model (LiNGAM) has shown promising results in various applications, it still faces the following challenges in the data with multiple latent confounders: 1) how to detect the latent confounders and 2) how to uncover the causal relations among observed and latent variables. To address these two challenges, we propose a hybrid causal discovery method for the LiNGAM with multiple latent confounders (MLCLiNGAM). First, we utilize the constraint-based method to learn the causal skeleton. Second, we identify the causal directions, by conducting regression and independence tests on the adjacent pairs in the causal skeleton. Third, we detect the latent confounders with the help of the maximal clique patterns raised by the latent confounders and reconstruct the causal structure with latent variables. Theoretical results show the correctness and efficiency of the algorithms. We conduct extensive experiments on synthetic and real data, which illustrates the efficiency and effectiveness of the proposed algorithms.

Elucidation of the mechanism of cognitive decline in mild cognitive impairment using causal discovery

Mild cognitive impairment (MCI) is the stage between the expected cognitive decline of normal aging and the more serious decline of dementia. Since MCI may increase risk of later developing dementia caused by Alzheimer's disease (AD) or other neurological conditions, it is important to detect and treat MCI early in order to prevent dementia. Causal discovery, which can visualize causal relationships (cause and effect) among data, has recently been attracting attention. One of its algorithms, the Linear Non-Gaussian Acyclic Model (LiNGAM), can extract causal relationships among variables from statistical data only, using probability distributions of variables that are generally non-Gaussian. In this study, we used LiNGAM to analyze gene expression data in the hippocampus of healthy subjects and of MCI patients, and also the Mini-Mental State Examination (MMSE) scores, which are used to assess cognitive decline. We found that cell adhesion molecule 4 (CADM4) gene regulates cognitive processes that are measured in terms of MMSE scores. Our results revealed a causal relationship between gene expression changes and MMSE scores, and allowed us to identify the genes responsible for cognitive decline..

Contemporaneous causality among residential housing prices of ten major Chinese cities

PurposeThis study aims to investigate dynamic relationships among residential housing price indices of ten major Chinese cities for the years 2005–2021.Design/methodology/approachUsing monthly data, this study uses vector error correction modeling and the directed acyclic graph for characterization of contemporaneous causality among the ten indices.FindingsThe PC algorithm identifies the causal pattern and the Linear Non-Gaussian Acyclic Model algorithm further determines the causal path, from which this study conducts innovation accounting analysis. Sophisticated price dynamics are found in price adjustment processes following price shocks, which are generally dominated by the top tiers of cities.Originality/valueThis study suggests that policies on residential housing prices in the long run might need to be planned with particular attention paid to these top tiers of cities.

Medical checkup data analysis method based on LiNGAM and its application to nonalcoholic fatty liver disease

Although medical checkup data would be useful for identifying unknown factors of disease progression, a causal relationship between checkup items should be taken into account for precise analysis. Missing values in medical checkup data must be appropriately imputed because checkup items vary from person to person, and items that have not been tested include missing values. In addition, the patients with target diseases or disorders are small in comparison with the total number of persons recorded in the data, which means medical checkup data is an imbalanced data analysis. We propose a new method for analyzing the causal relationship in medical checkup data to discover disease progression factors based on a linear non-Gaussian acyclic model (LiNGAM), a machine learning technique for causal inference. In the proposed method, specific regression coefficients calculated through LiNGAM were compared to estimate the causal strength of the checkup items on disease progression, which is referred to as LiNGAM-beta. We also propose an analysis framework consisting of LiNGAM-beta, collaborative filtering (CF), and a sampling approach for causal inference of medical checkup data. CF and the sampling approach are useful for missing value imputation and balancing of the data distribution. We applied the proposed analysis framework to medical checkup data for identifying factors of Nonalcoholic fatty liver disease (NAFLD) development. The checkup items related to metabolic syndrome and age showed high causal effects on NAFLD severity. The level of blood urea nitrogen (BUN) would have a negative effect on NAFLD severity. Snoring frequency, which is associated with obstructive sleep apnea, affected NAFLD severity, particularly in the male group. Sleep duration also affected NAFLD severity in persons over fifty years old. These analysis results are consistent with previous reports about the causes of NAFLD; for example, NAFLD and metabolic syndrome are mutual and bi-directionally related, and BUN has a negative effect on NAFLD progression. Thus, our analysis result is plausible. The proposed analysis framework including LiNGAM-beta can be applied to various medical checkup data and will contribute to discovering unknown disease factors.