A Logical Characterization of Constraint-Based Causal Discovery

We present a novel approach to constraint-based causal discovery, that takes the form of straightforward logical inference, applied to a list of simple, logical statements about causal relations that are derived directly from observed (in)dependencies. It is both sound and complete, in the sense that all invariant features of the corresponding partial ancestral graph (PAG) are identified, even in the presence of latent variables and selection bias. The approach shows that every identifiable causal relation corresponds to one of just two fundamental forms. More importantly, as the basic building blocks of the method do not rely on the detailed (graphical) structure of the corresponding PAG, it opens up a range of new opportunities, including more robust inference, detailed accountability, and application to large models

Causal Inference through a Witness Protection Program

One of the most fundamental problems in causal inference is the estimation of a causal effect when variables are confounded. This is difficult in an observational study because one has no direct evidence that all confounders have been adjusted for. We introduce a novel approach for estimating causal effects that exploits observational conditional independencies to suggest weak'' paths in a unknown causal graph. The widely used faithfulness condition of Spirtes et al. is relaxed to allow for varying degrees of path cancellations'' that will imply conditional independencies but do not rule out the existence of confounding causal paths. The outcome is a posterior distribution over bounds on the average causal effect via a linear programming approach and Bayesian inference. We claim this approach should be used in regular practice to complement other default tools in observational studies

Causal Inference through a Witness Protection Program

One of the most fundamental problems in causal inference is the estimation of a causal effect when variables are confounded. This is difficult in an observational study, because one has no direct evidence that all confounders have been adjusted for. We introduce a novel approach for estimating causal effects that exploits observational conditional independencies to suggest "weak" paths in a unknown causal graph. The widely used faithfulness condition of Spirtes et al. is relaxed to allow for varying degrees of "path cancellations" that imply conditional independencies but do not rule out the existence of confounding causal paths. The outcome is a posterior distribution over bounds on the average causal effect via a linear programming approach and Bayesian inference. We claim this approach should be used in regular practice along with other default tools in observational studies.Comment: 41 pages, 7 figure

Challenges and Opportunities with Causal Discovery Algorithms: Application to Alzheimer’s Pathophysiology

© 2020, The Author(s). Causal Structure Discovery (CSD) is the problem of identifying causal relationships from large quantities of data through computational methods. With the limited ability of traditional association-based computational methods to discover causal relationships, CSD methodologies are gaining popularity. The goal of the study was to systematically examine whether (i) CSD methods can discover the known causal relationships from observational clinical data and (ii) to offer guidance to accurately discover known causal relationships. We used Alzheimer’s disease (AD), a complex progressive disease, as a model because the well-established evidence provides a “gold-standard” causal graph for evaluation. We evaluated two CSD methods, Fast Causal Inference (FCI) and Fast Greedy Equivalence Search (FGES) in their ability to discover this structure from data collected by the Alzheimer’s Disease Neuroimaging Initiative (ADNI). We used structural equation models (which is not designed for CSD) as control. We applied these methods under three scenarios defined by increasing amounts of background knowledge provided to the methods. The methods were evaluated by comparing the resulting causal relationships with the “gold standard” graph that was constructed from literature. Dedicated CSD methods managed to discover graphs that nearly coincided with the gold standard. For best results, CSD algorithms should be used with longitudinal data providing as much prior knowledge as possible

Bayesian network analysis of multi-compartmentalized immune responses in a murine model of sepsis and direct lung injury

Abstract Background Inflammatory disease processes involve complex and interrelated systems of mediators. Determining the causal relationships among these mediators becomes more complicated when two, concurrent inflammatory conditions occur. In those cases, the outcome may also be dependent upon the timing, severity and compartmentalization of the insults. Unfortunately, standard methods of experimentation and analysis of data sets may investigate a single scenario without uncovering many potential associations among mediators. However, Bayesian network analysis is able to model linear, nonlinear, combinatorial, and stochastic relationships among variables to explore complex inflammatory disease systems. In these studies, we modeled the development of acute lung injury from an indirect insult (sepsis induced by cecal ligation and puncture) complicated by a direct lung insult (aspiration). To replicate multiple clinical situations, the aspiration injury was delivered at different severities and at different time intervals relative to the septic insult. For each scenario, we measured numerous inflammatory cell types and cytokines in samples from the local compartments (peritoneal and bronchoalveolar lavage fluids) and the systemic compartment (plasma). We then analyzed these data by Bayesian networks and standard methods. Results Standard data analysis demonstrated that the lung injury was actually reduced when two insults were involved as compared to one lung injury alone. Bayesian network analysis determined that both the severity of lung insult and presence of sepsis influenced neutrophil recruitment and the amount of injury to the lung. However, the levels of chemoattractant cytokines responsible for neutrophil recruitment were more strongly linked to the timing and severity of the lung insult compared to the presence of sepsis. This suggests that something other than sepsis-driven exacerbation of chemokine levels was influencing the lung injury, contrary to previous theories. Conclusions To our knowledge, these studies are the first to use Bayesian networks together with experimental studies to examine the pathogenesis of sepsis-associated lung injury. Compared to standard statistical analysis and inference, these analyses elucidated more intricate relationships among the mediators, immune cells and insult-related variables (timing, compartmentalization and severity) that cause lung injury. Bayesian networks are an effective tool for evaluating complex models of inflammation.http://deepblue.lib.umich.edu/bitstream/2027.42/113666/1/13104_2015_Article_1488.pd