Optimal adjustment sets for causal query estimation in partially observed biomolecular networks

Author:

Mohammad-Taheri Sara1,Tewari Vartika1,Kapre Rohan1,Rahiminasab Ehsan2,Sachs Karen345,Tapley Hoyt Charles6,Zucker Jeremy7,Vitek Olga1

Affiliation:

1. Khoury College of Computer Sciences, Northeastern University , Boston, MA 02115, USA

2. Google, Cambridge , MA 02142, USA

3. Next Generation Analytics, Palo Alto California , USA

4. Modulo Bio Inc , Los Altos, California, USA

5. Answer ALS , New Orleans, LA, USA

6. Laboratory of Systems Pharmacology, Harvard Medical School , Boston, Massachusetts, USA

7. Pacific Northwest National Laboratory , Richland, Washington 99354, USA

Abstract

Abstract Causal query estimation in biomolecular networks commonly selects a ‘valid adjustment set’, i.e. a subset of network variables that eliminates the bias of the estimator. A same query may have multiple valid adjustment sets, each with a different variance. When networks are partially observed, current methods use graph-based criteria to find an adjustment set that minimizes asymptotic variance. Unfortunately, many models that share the same graph topology, and therefore same functional dependencies, may differ in the processes that generate the observational data. In these cases, the topology-based criteria fail to distinguish the variances of the adjustment sets. This deficiency can lead to sub-optimal adjustment sets, and to miss-characterization of the effect of the intervention. We propose an approach for deriving ‘optimal adjustment sets’ that takes into account the nature of the data, bias and finite-sample variance of the estimator, and cost. It empirically learns the data generating processes from historical experimental data, and characterizes the properties of the estimators by simulation. We demonstrate the utility of the proposed approach in four biomolecular Case studies with different topologies and different data generation processes. The implementation and reproducible Case studies are at https://github.com/srtaheri/OptimalAdjustmentSet.

Funder

DOE

Predictive Phenomics Initiative at Pacific Northwest National Laboratory

Laboratory Directed Research and Development Program

Department of Energy

Defense Advanced Research

Young Faculty

Automating Scientific Knowledge Extraction and Modeling

NIH

Publisher

Oxford University Press (OUP)

Subject

Computational Mathematics,Computational Theory and Mathematics,Computer Science Applications,Molecular Biology,Biochemistry,Statistics and Probability

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