Nonparametric Identification and Inference for Counterfactual Distributions with Confounding

We propose nonparametric identification and semiparametric estimation of joint potential outcome distributions in the presence of confounding. First, in settings with observed confounding, we derive tighter, covariate-informed bounds on the joint distribution by leveraging conditional copulas. To overcome the non-differentiability of bounding min/max operators, we establish the asymptotic properties for both a direct estimator with polynomial margin condition and a smooth approximation with log-sum-exp operator, facilitating valid inference for individual-level effects under the canonical rank-preserving assumption. Second, we tackle the challenge of unmeasured confounding by introducing a causal representation learning framework. By utilizing instrumental variables, we prove the nonparametric identifiability of the latent confounding subspace under injectivity and completeness conditions. We develop a ``triple machine learning" estimator that employs cross-fitting scheme to sequentially handle the learned representation, nuisance parameters, and target functional. We characterize the asymptotic distribution with variance inflation induced by representation learning error, and provide conditions for semiparametric efficiency. We also propose a practical VAE-based algorithm for confounding representation learning. Simulations and real-world analysis validate the effectiveness of proposed methods. By bridging classical semiparametric theory with modern representation learning, this work provides a robust statistical foundation for distributional and counterfactual inference in complex causal systems.

When Selection Meets Intervention: Additional Complexities in Causal Discovery

We address the common yet often-overlooked selection bias in interventional studies, where subjects are selectively enrolled into experiments. For instance, participants in a drug trial are usually patients of the relevant disease; A/B tests on mobile applications target existing users only, and gene perturbation studies typically focus on specific cell types, such as cancer cells. Ignoring this bias leads to incorrect causal discovery results. Even when recognized, the existing paradigm for interventional causal discovery still fails to address it. This is because subtle differences in when and where interventions happen can lead to significantly different statistical patterns. We capture this dynamic by introducing a graphical model that explicitly accounts for both the observed world (where interventions are applied) and the counterfactual world (where selection occurs while interventions have not been applied). We characterize the Markov property of the model, and propose a provably sound algorithm to identify causal relations as well as selection mechanisms up to the equivalence class, from data with soft interventions and unknown targets. Through synthetic and real-world experiments, we demonstrate that our algorithm effectively identifies true causal relations despite the presence of selection bias.

Rethinking the BERT-like Pretraining for DNA Sequences

With the success of large-scale pretraining in NLP, there is an increasing trend of applying it to the domain of life sciences. In particular, pretraining methods based on DNA sequences have garnered growing attention due to their potential to capture generic information about genes. However, existing pretraining methods for DNA sequences largely rely on direct adoptions of BERT pretraining from NLP, lacking a comprehensive understanding and a specifically tailored approach. To address this research gap, we first conducted a series of exploratory experiments and gained several insightful observations: 1) In the fine-tuning phase of downstream tasks, when using K-mer overlapping tokenization instead of K-mer non-overlapping tokenization, both overlapping and non-overlapping pretraining weights show consistent performance improvement.2) During the pre-training process, using K-mer overlapping tokenization quickly produces clear K-mer embeddings and reduces the loss to a very low level, while using K-mer non-overlapping tokenization results in less distinct embeddings and continuously decreases the loss. 3) Using overlapping tokenization causes the self-attention in the intermediate layers of pre-trained models to tend to overly focus on certain tokens, reflecting that these layers are not adequately optimized. In summary, overlapping tokenization can benefit the fine-tuning of downstream tasks but leads to inadequate pretraining with fast convergence. To unleash the pretraining potential, we introduce a novel approach called RandomMask, which gradually increases the task difficulty of BERT-like pretraining by continuously expanding its mask boundary, forcing the model to learn more knowledge. RandomMask is simple but effective, achieving top-tier performance across 26 datasets of 28 datasets spanning 7 downstream tasks.