Predicting drug-target interactions by measuring confidence with consistent causal neighborhood interventions.

Predicting drug-target interactions (DTI) is a crucial stage in drug discovery and development. Understanding the interaction between drugs and targets is essential for pinpointing the specific relationship between drug molecules and targets, akin to solving a link prediction problem using information technology. While knowledge graph (KG) and knowledge graph embedding (KGE) methods have been rapid advancements and demonstrated impressive performance in drug discovery, they often lack authenticity and accuracy in identifying DTI. This leads to increased misjudgment rates and reduced efficiency in drug development. To address these challenges, our focus lies in refining the accuracy of DTI prediction models through KGE, with a specific emphasis on causal intervention confidence measures (CI). These measures aim to assess triplet scores, enhancing the precision of the predictions. Comparative experiments conducted on three datasets and utilizing 9 KGE models reveal that our proposed confidence measure approach via causal intervention, significantly improves the accuracy of DTI link prediction compared to traditional approaches. Furthermore, our experimental analysis delves deeper into the embedding of intervention values, offering valuable insights for guiding the design and development of subsequent drug development experiments. As a result, our predicted outcomes serve as valuable guidance in the pursuit of more efficient drug development processes.

Toward Unique and Unbiased Causal Effect Estimation From Data With Hidden Variables.

Causal effect estimation from observational data is a crucial but challenging task. Currently, only a limited number of data-driven causal effect estimation methods are available. These methods either provide only a bound estimation of causal effects of treatment on the outcome or generate a unique estimation of the causal effect but making strong assumptions on data and having low efficiency. In this article, we identify a problem setting with the Cause Or Spouse of the treatment Only (COSO) variable assumption and propose an approach to achieving a unique and unbiased estimation of causal effects from data with hidden variables. For the approach, we have developed the theorems to support the discovery of the proper covariate sets for confounding adjustment (adjustment sets). Based on the theorems, two algorithms are proposed for finding the proper adjustment sets from data with hidden variables to obtain unbiased and unique causal effect estimation. Experiments with synthetic datasets generated using five benchmark Bayesian networks and four real-world datasets have demonstrated the efficiency and effectiveness of the proposed algorithms, indicating the practicability of the identified problem setting and the potential of the proposed approach in real-world applications.

Discovering Ancestral Instrumental Variables for Causal Inference From Observational Data.

Instrumental variable (IV) is a powerful approach to inferring the causal effect of a treatment on an outcome of interest from observational data even when there exist latent confounders between the treatment and the outcome. However, existing IV methods require that an IV is selected and justified with domain knowledge. An invalid IV may lead to biased estimates. Hence, discovering a valid IV is critical to the applications of IV methods. In this article, we study and design a data-driven algorithm to discover valid IVs from data under mild assumptions. We develop the theory based on partial ancestral graphs (PAGs) to support the search for a set of candidate ancestral IVs (AIVs), and for each possible AIV, the identification of its conditioning set. Based on the theory, we propose a data-driven algorithm to discover a pair of IVs from data. The experiments on synthetic and real-world datasets show that the developed IV discovery algorithm estimates accurate estimates of causal effects in comparison with the state-of-the-art IV-based causal effect estimators.