arXiv subjects

Sara Mohammad-Taheri

Publications and source records attributed to Sara Mohammad-Taheri.

3 recordsLinked to original sources

arXiv2022

Experimental design for causal query estimation in partially observed biomolecular networks

Estimating a causal query from observational data is an essential task in the analysis of biomolecular networks. Estimation takes as input a network topology, a query estimation method, and observational measurements on the network variables. However, estimations involving many variables can be experimentally expensive, and computationally intractable. Moreover, using the full set of variables can be detrimental, leading to bias, or increasing the variance in the estimation. Therefore, designing an experiment based on a well-chosen subset of network components can increase estimation accuracy, and reduce experimental and computational costs. We propose a simulation-based algorithm for selecting sub-networks that support unbiased estimators of the causal query under a constraint of cost, ranked with respect to the variance of the estimators. The simulations are constructed based on historical experimental data, or based on known properties of the biological system. Three case studies demonstrated the effectiveness of well-chosen network subsets for estimating causal queries from observational data. All the case studies are reproducible and available at https://github.com/srtaheri/Simplified_LVM.

q-bio.BM↗

arXiv2022

Do-calculus enables estimation of causal effects in partially observed biomolecular pathways

Estimating causal queries, such as changes in protein abundance in response to a perturbation, is a fundamental task in the analysis of biomolecular pathways. The estimation requires experimental measurements on the pathway components. However, in practice many pathway components are left unobserved (latent) because they are either unknown, or difficult to measure. Latent variable models (LVMs) are well-suited for such estimation. Unfortunately, LVM-based estimation of causal queries can be inaccurate when parameters of the latent variables are not uniquely identified, or when the number of latent variables is misspecified. This has limited the use of LVMs for causal inference in biomolecular pathways. In this manuscript, we propose a general and practical approach for LVM-based estimation of causal queries. We prove that, despite the challenges above, LVM-based estimators of causal queries are accurate if the queries are identifiable according to Pearl's do-calculus, and describe an algorithm for its estimation. We illustrate the breadth and the practical utility of this approach for estimating causal queries in four synthetic and two experimental case studies, where structures of biomolecular pathways challenge the existing methods for causal query estimation. The code and the data documenting all the case studies are available at \url{https://github.com/srtaheri/LVMwithDoCalculus}

cs.LG↗

arXiv2021

Leveraging Structured Biological Knowledge for Counterfactual Inference: a Case Study of Viral Pathogenesis

Counterfactual inference is a useful tool for comparing outcomes of interventions on complex systems. It requires us to represent the system in form of a structural causal model, complete with a causal diagram, probabilistic assumptions on exogenous variables, and functional assignments. Specifying such models can be extremely difficult in practice. The process requires substantial domain expertise, and does not scale easily to large systems, multiple systems, or novel system modifications. At the same time, many application domains, such as molecular biology, are rich in structured causal knowledge that is qualitative in nature. This manuscript proposes a general approach for querying a causal biological knowledge graph, and converting the qualitative result into a quantitative structural causal model that can learn from data to answer the question. We demonstrate the feasibility, accuracy and versatility of this approach using two case studies in systems biology. The first demonstrates the appropriateness of the underlying assumptions and the accuracy of the results. The second demonstrates the versatility of the approach by querying a knowledge base for the molecular determinants of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced cytokine storm, and performing counterfactual inference to estimate the causal effect of medical countermeasures for severely ill patients.

q-bio.QM↗