Deep Causal Graphs for Causal Inference, Black-Box Explainability and Fairness

Causal Estimation is usually tackled as a two-step process: identification, to transform a causal query into a statistical estimand, and modelling, to compute this estimand by using data. This reliance on the derived statistical estimand makes these methods ad hoc, used to answer one and only one query. We present an alternative framework called Deep Causal Graphs: with a single model, it answers any identifiable causal query without compromising on performance, thanks to the use of Normalizing Causal Flows, and outputs complex counterfactual distributions instead of single-point estimations of their expected value. We conclude with applications of the framework to Machine Learning Explainability and Fairness.

Normalized Multivariate Time Series Causality Analysis and Causal Graph Reconstruction

Causality analysis is an important problem lying at the heart of science, and is of particular importance in data science and machine learning. An endeavor during the past 16 years viewing causality as a real physical notion so as to formulate it from first principles, however, seems to have gone unnoticed. This study introduces to the community this line of work, with a long-due generalization of the information flow-based bivariate time series causal inference to multivariate series, based on the recent advance in theoretical development. The resulting formula is transparent, and can be implemented as a computationally very efficient algorithm for application. It can be normalized and tested for statistical significance. Different from the previous work along this line where only information flows are estimated, here an algorithm is also implemented to quantify the influence of a unit to itself. While this forms a challenge in some causal inferences, here it comes naturally, and hence the identification of self-loops in a causal graph is fulfilled automatically as the causalities along edges are inferred. To demonstrate the power of the approach, presented here are two applications in extreme situations. The first is a network of multivariate processes buried in heavy noises (with the noise-to-signal ratio exceeding 100), and the second a network with nearly synchronized chaotic oscillators. In both graphs, confounding processes exist. While it seems to be a challenge to reconstruct from given series these causal graphs, an easy application of the algorithm immediately reveals the desideratum. Particularly, the confounding processes have been accurately differentiated. Considering the surge of interest in the community, this study is very timely.

MRPC: An R Package for Inference of Causal Graphs

Understanding the causal relationships between variables is a central goal of many scientific inquiries. Causal relationships may be represented by directed edges in a graph (or equivalently, a network). In biology, for example, gene regulatory networks may be viewed as a type of causal networks, where X→Y represents gene X regulating (i.e., being causal to) gene Y. However, existing general-purpose graph inference methods often result in a high number of false edges, whereas current causal inference methods developed for observational data in genomics can handle only limited types of causal relationships. We present MRPC (a PC algorithm with the principle of Mendelian Randomization), an R package that learns causal graphs with improved accuracy over existing methods. Our algorithm builds on the powerful PC algorithm (named after its developers Peter Spirtes and Clark Glymour), a canonical algorithm in computer science for learning directed acyclic graphs. The improvements in MRPC result in increased accuracy in identifying v-structures (i.e., X→Y←Z), and robustness to how the nodes are arranged in the input data. In the special case of genomic data that contain genotypes and phenotypes (e.g., gene expression) at the individual level, MRPC incorporates the principle of Mendelian randomization as constraints on edge direction to help orient the edges. MRPC allows for inference of causal graphs not only for general purposes, but also for biomedical data where multiple types of data may be input to provide evidence for causality. The R package is available on CRAN and is a free open-source software package under a GPL (≥2) license.

Homeostatic Property Cluster Theory without Homeostatic Mechanisms: Two Recent Attempts and their Costs

The homeostatic property cluster theory (HPC) is widely influential for its ability to account for many natural-kind terms in the life sciences. However, the notion of homeostatic mechanism has never been fully explicated. In 2009, Carl Craver interpreted the notion in the sense articulated in discussions on mechanistic explanation and pointed out that the HPC account equipped with such notion invites interest-relativity. In this paper, we analyze two recent refinements on HPC: one that avoids any reference to the causes of the clustering of properties and one that replaces homeostatic mechanisms with causal networks represented by causal graphs. We argue that the former is too slender to account for some inductive inference in science and the latter, thicker account invites interest-relativity, as the original HPC does. This suggests that human interest will be an un-eliminative part of a satisfactory account of natural kindness. We conclude by discussing the implication of interest-relativity to the naturalness, reality, or objectivity of kinds and indicating an overlooked aspect of natural kinds that requires further studies.

DCI: learning causal differences between gene regulatory networks

Summary Designing interventions to control gene regulation necessitates modeling a gene regulatory network by a causal graph. Currently, large-scale gene expression datasets from different conditions, cell types, disease states, and developmental time points are being collected. However, application of classical causal inference algorithms to infer gene regulatory networks based on such data is still challenging, requiring high sample sizes and computational resources. Here, we describe an algorithm that efficiently learns the differences in gene regulatory mechanisms between different conditions. Our difference causal inference (DCI) algorithm infers changes (i.e. edges that appeared, disappeared, or changed weight) between two causal graphs given gene expression data from the two conditions. This algorithm is efficient in its use of samples and computation since it infers the differences between causal graphs directly without estimating each possibly large causal graph separately. We provide a user-friendly Python implementation of DCI and also enable the user to learn the most robust difference causal graph across different tuning parameters via stability selection. Finally, we show how to apply DCI to single-cell RNA-seq data from different conditions and cell states, and we also validate our algorithm by predicting the effects of interventions. Availability and implementation Python package freely available at http://uhlerlab.github.io/causaldag/dci. Supplementary information Supplementary data are available at Bioinformatics online.

A case study and proposal for publishing directed acyclic graphs: The effectiveness of the quadrivalent HPV vaccine in perinatally HIV exposed girls

Background: Developing a causal graph is an important step in etiologic research planning and can be used to highlight data flaws and irreparable bias and confounding. Recent findings have suggested that the human papillomavirus (HPV) vaccine is less effective in protection against HPV associated disease in a population of girls living with HIV. Development: In order to understand the relationship between HIV status and HPV vaccine effectiveness, it is important to outline the key assumptions of the causal mechanisms before designing a study to investigate the effect of the HPV vaccine in girls living with HIV infection. Application: We present a causal graph to describe our assumptions and proposed approach to explore this relationship. We hope to obtain feedback on our assumptions prior to data analysis and exemplify the process for designing an etiologic study.Conclusion: The approach we lay out in this paper may be useful for other researchers who have an interest in using causal graphs to describe and assess assumptions in their own research prior to undergoing data collection and/or analysis.

Causal graphs for the analysis of genetic cohort data

The increasing availability of genetic cohort data has led to many genome-wide association studies (GWAS) successfully identifying genetic associations with an ever-expanding list of phenotypic traits. Association, however, does not imply causation, and therefore methods have been developed to study the issue of causality. Under additional assumptions, Mendelian randomization (MR) studies have proved popular in identifying causal effects between two phenotypes, often using GWAS summary statistics. Given the widespread use of these methods, it is more important than ever to understand, and communicate, the causal assumptions upon which they are based, so that methods are transparent, and findings are clinically relevant. Causal graphs can be used to represent causal assumptions graphically and provide insights into the limitations associated with different analysis methods. Here we review GWAS and MR from a causal perspective, to build up intuition for causal diagrams in genetic problems. We also examine issues of confounding by ancestry and comment on approaches for dealing with such confounding, as well as discussing approaches for dealing with selection biases arising from study design.