Methods for causal inference from gene perturbation experiments and validation

Proc Natl Acad Sci U S A. 2016 Jul 5;113(27):7361-8. doi: 10.1073/pnas.1510493113.

Abstract

Inferring causal effects from observational and interventional data is a highly desirable but ambitious goal. Many of the computational and statistical methods are plagued by fundamental identifiability issues, instability, and unreliable performance, especially for large-scale systems with many measured variables. We present software and provide some validation of a recently developed methodology based on an invariance principle, called invariant causal prediction (ICP). The ICP method quantifies confidence probabilities for inferring causal structures and thus leads to more reliable and confirmatory statements for causal relations and predictions of external intervention effects. We validate the ICP method and some other procedures using large-scale genome-wide gene perturbation experiments in Saccharomyces cerevisiae The results suggest that prediction and prioritization of future experimental interventions, such as gene deletions, can be improved by using our statistical inference techniques.

Keywords: genome database validation; graphical models; interventional–observational data; invariant causal prediction.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Algorithms
  • Flow Cytometry
  • Gene Deletion
  • Models, Genetic*
  • Saccharomyces cerevisiae
  • Software
  • Statistics as Topic*