Mitigating pathogenesis for target discovery and disease subtyping.

Eric V Strobl, Thomas A Lasko, Eric R Gamazon
Author Information
  1. Eric V Strobl: Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, 1601 23rd Avenue South, Nashville, TN 37232, United States of America. Electronic address: eric.strobl@vumc.org.
  2. Thomas A Lasko: Department of Biomedical Informatics, Vanderbilt University Medical Center, United States of America.
  3. Eric R Gamazon: Department of Medicine, Vanderbilt University Medical Center, United States of America.

Abstract

Treatments ideally mitigate pathogenesis, or the detrimental effects of the root causes of disease. However, existing definitions of treatment effect fail to account for pathogenic mechanism. We therefore introduce the Treated Root causal Effects (TRE) metric which measures the ability of a treatment to modify root causal effects. We leverage TREs to automatically identify treatment targets and cluster patients who respond similarly to treatment. The proposed algorithm learns a partially linear causal model to extract the root causal effects of each variable and then estimates TREs for target discovery and downstream subtyping. We maintain interpretability even without assuming an invertible structural equation model. Experiments across a range of datasets corroborate the generality of the proposed approach.

Keywords

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Grants

  1. R01 HG011138/NHGRI NIH HHS
  2. R21 LM013807/NLM NIH HHS

MeSH Term

Humans
Models, Theoretical
Algorithms

Word Cloud

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