Methods for causal inference from gene perturbation experiments and validation

TY - JOUR

T1 - Methods for causal inference from gene perturbation experiments and validation

AU - Meinshausen, Nicolai

AU - Hauser, Alain

AU - Mooij, Joris M

AU - Peters, Jonas

AU - Versteeg, Philip

AU - Bühlmann, Peter

PY - 2016/7/5

Y1 - 2016/7/5

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.1073/pnas.1510493113

DO - 10.1073/pnas.1510493113

M3 - Journal article

C2 - 27382150

SN - 0027-8424

VL - 113

SP - 7361

EP - 7368

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 27

ER -