J Biomed Inform. 2024 Jan 6:104585. doi: 10.1016/j.jbi.2024.104585. Online ahead of print.

ABSTRACT

OBJECTIVE: Root causes of disease intuitively correspond to root vertices of a causal model that increase the likelihood of a diagnosis. This description of a root cause nevertheless lacks the rigorous mathematical formulation needed for the development of computer algorithms designed to automatically detect root causes from data. We seek a definition of patient-specific root causes of disease that models the intuitive procedure routinely utilized by physicians to uncover root causes in the clinic.

METHODS: We use structural equation models, interventional counterfactuals and the recently developed mathematical formalization of backtracking counterfactuals to propose a counterfactual formulation of patient-specific root causes of disease matching clinical intuition.

RESULTS: We introduce a definition of patient-specific root causes of disease that climbs to the third rung of Pearl’s Ladder of Causation and matches clinical intuition given factual patient data and a working causal model. We then show how to assign a root causal contribution score to each variable using Shapley values from explainable artificial intelligence.

CONCLUSION: The proposed counterfactual formulation of patient-specific root causes of disease accounts for noisy labels, adapts to disease prevalence and admits fast computation without the need for counterfactual simulation.

PMID:38191012 | DOI:10.1016/j.jbi.2024.104585