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Practical Causal Evaluation Metrics for Biological Networks

Sato, Noriaki, Scutari, Marco, Kawano, Shuichi, Yamaguchi, Rui, Imoto, Seiya

arXiv.org Artificial Intelligence

Estimating causal networks from biological data is a critical step in systems biology. When evaluating the inferred network, assessing the networks based on their intervention effects is particularly important for downstream probabilistic reasoning and the identification of potential drug targets. In the context of gene regulatory network inference, biological databases are often used as reference sources. These databases typically describe relationships in a qualitative rather than quantitative manner. However, few evaluation metrics have been developed that take this qualitative nature into account. To address this, we developed a metric, the sign-augmented Structural Intervention Distance (sSID), and a weighted sSID that incorporates the net effects of the intervention. Through simulations and analyses of real transcriptomic datasets, we found that our proposed metrics could identify a different algorithm as optimal compared to conventional metrics, and the network selected by sSID had a superior performance in the classification task of clinical covariates using transcriptomic data. This suggests that sSID can distinguish networks that are structurally correct but functionally incorrect, highlighting its potential as a more biologically meaningful and practical evaluation metric.



Causal Mediation Analysis with Multiple Mediators: A Simulation Approach

Zhou, Jesse, Wodtke, Geoffrey T.

arXiv.org Machine Learning

Analyses of causal mediation often involve exposure-induced confounders or, relatedly, multiple mediators. In such applications, researchers aim to estimate a variety of different quantities, including interventional direct and indirect effects, multivariate natural direct and indirect effects, and/or path-specific effects. This study introduces a general approach to estimating all these quantities by simulating potential outcomes from a series of distribution models for each mediator and the outcome. Building on similar methods developed for analyses with only a single mediator (Imai et al. 2010), we first outline how to implement this approach with parametric models. The parametric implementation can accommodate linear and nonlinear relationships, both continuous and discrete mediators, and many different types of outcomes. However, it depends on correct specification of each model used to simulate the potential outcomes. To address the risk of misspecification, we also introduce an alternative implementation using a novel class of nonparametric models, which leverage deep neural networks to approximate the relevant distributions without relying on strict assumptions about functional form. We illustrate both methods by reanalyzing the effects of media framing on attitudes toward immigration (Brader et al. 2008) and the effects of prenatal care on preterm birth (VanderWeele et al. 2014).


CodeSCM: Causal Analysis for Multi-Modal Code Generation

Gupta, Mukur, Bhatt, Noopur, Jana, Suman

arXiv.org Artificial Intelligence

In this paper, we propose CodeSCM, a Structural Causal Model (SCM) for analyzing multi-modal code generation using large language models (LLMs). By applying interventions to CodeSCM, we measure the causal effects of different prompt modalities, such as natural language, code, and input-output examples, on the model. CodeSCM introduces latent mediator variables to separate the code and natural language semantics of a multi-modal code generation prompt. Using the principles of Causal Mediation Analysis on these mediators we quantify direct effects representing the model's spurious leanings. We find that, in addition to natural language instructions, input-output examples significantly influence code generation.


PCM Selector: Penalized Covariate-Mediator Selection Operator for Evaluating Linear Causal Effects

Nanmo, Hisayoshi, Kuroki, Manabu

arXiv.org Artificial Intelligence

For a data-generating process for random variables that can be described with a linear structural equation model, we consider a situation in which (i) a set of covariates satisfying the back-door criterion cannot be observed or (ii) such a set can be observed, but standard statistical estimation methods cannot be applied to estimate causal effects because of multicollinearity/high-dimensional data problems. We propose a novel two-stage penalized regression approach, the penalized covariate-mediator selection operator (PCM Selector), to estimate the causal effects in such scenarios. Unlike existing penalized regression analyses, when a set of intermediate variables is available, PCM Selector provides a consistent or less biased estimator of the causal effect. In addition, PCM Selector provides a variable selection procedure for intermediate variables to obtain better estimation accuracy of the causal effects than does the back-door criterion.


Robust Causal Analysis of Linear Cyclic Systems With Hidden Confounders

Lorbeer, Boris, Küpper, Axel

arXiv.org Machine Learning

We live in a world full of complex systems which we need to improve our understanding of. To accomplish this, purely probabilistic investigations are often not enough. They are only the first step and must be followed by learning the system's underlying mechanisms. This is what the discipline of causality is concerned with. Many of those complex systems contain feedback loops which means that our methods have to allow for cyclic causal relations. Furthermore, systems are rarely sufficiently isolated, which means that there are usually hidden confounders, i.e., unmeasured variables that each causally affects more than one measured variable. Finally, data is often distorted by contaminating processes, and we need to apply methods that are robust against such distortions. That's why we consider the robustness of LLC, see \cite{llc}, one of the few causal analysis methods that can deal with cyclic models with hidden confounders. Following a theoretical analysis of LLC's robustness properties, we also provide robust extensions of LLC. To facilitate reproducibility and further research in this field, we make the source code publicly available.


Deep Causal Inference for Point-referenced Spatial Data with Continuous Treatments

Jiang, Ziyang, Calhoun, Zach, Liu, Yiling, Duan, Lei, Carlson, David

arXiv.org Artificial Intelligence

Causal reasoning is often challenging with spatial data, particularly when handling high-dimensional inputs. To address this, we propose a neural network (NN) based framework integrated with an approximate Gaussian process to manage spatial interference and unobserved confounding. Additionally, we adopt a generalized propensity-score-based approach to address partially observed outcomes when estimating causal effects with continuous treatments. We evaluate our framework using synthetic, semi-synthetic, and real-world data inferred from satellite imagery. Our results demonstrate that NN-based models significantly outperform linear spatial regression models in estimating causal effects. Furthermore, in real-world case studies, NN-based models offer more reasonable predictions of causal effects, facilitating decision-making in relevant applications.


Causal reasoning in difference graphs

Assaad, Charles K.

arXiv.org Artificial Intelligence

In epidemiology, understanding causal mechanisms across different populations is essential for designing effective public health interventions. Recently, difference graphs have been introduced as a tool to visually represent causal variations between two distinct populations. While there has been progress in inferring these graphs from data through causal discovery methods, there remains a gap in systematically leveraging their potential to enhance causal reasoning. This paper addresses that gap by establishing conditions for identifying causal changes and effects using difference graphs and observational data. It specifically focuses on identifying total causal changes and total effects in a nonparametric framework, as well as direct causal changes and direct effects in a linear context. In doing so, it provides a novel approach to causal reasoning that holds potential for various public health applications.


Identifying macro conditional independencies and macro total effects in summary causal graphs with latent confounding

Ferreira, Simon, Assaad, Charles K.

arXiv.org Artificial Intelligence

Understanding causal relationships in dynamic systems is essential for numerous scientific fields, including epidemiology, economics, and biology. While causal inference methods have been extensively studied, they often rely on fully specified causal graphs, which may not always be available or practical in complex dynamic systems. Partially specified causal graphs, such as summary causal graphs (SCGs), provide a simplified representation of causal relationships, omitting temporal information and focusing on high-level causal structures. This simplification introduces new challenges concerning the types of queries of interest: macro queries, which involve relationships between clusters represented as vertices in the graph, and micro queries, which pertain to relationships between variables that are not directly visible through the vertices of the graph. In this paper, we first clearly distinguish between macro conditional independencies and micro conditional independencies and between macro total effects and micro total effects. Then, we demonstrate the soundness and completeness of the d-separation to identify macro conditional independencies in SCGs. Furthermore, we establish that the do-calculus is sound and complete for identifying macro total effects in SCGs. Conversely, we also show through various examples that these results do not hold when considering micro conditional independencies and micro total effects.


Toward identifiability of total effects in summary causal graphs with latent confounders: an extension of the front-door criterion

Assaad, Charles K.

arXiv.org Artificial Intelligence

Conducting experiments to estimate total effects can be challenging due to cost, ethical concerns, or practical limitations. As an alternative, researchers often rely on causal graphs to determine if it is possible to identify these effects from observational data. Identifying total effects in fully specified non-temporal causal graphs has garnered considerable attention, with Pearl's front-door criterion enabling the identification of total effects in the presence of latent confounding even when no variable set is sufficient for adjustment. However, specifying a complete causal graph is challenging in many domains. Extending these identifiability results to partially specified graphs is crucial, particularly in dynamic systems where causal relationships evolve over time. This paper addresses the challenge of identifying total effects using a specific and well-known partially specified graph in dynamic systems called a summary causal graph, which does not specify the temporal lag between causal relations and can contain cycles. In particular, this paper presents sufficient graphical conditions for identifying total effects from observational data, even in the presence of hidden confounding and when no variable set is sufficient for adjustment, contributing to the ongoing effort to understand and estimate causal effects from observational data using summary causal graphs.