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Stefan Schrod

Publications and source records attributed to Stefan Schrod.

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Querying Counterfactuals on Tissue Graphs with Supervised Disentanglement

Tissue graph counterfactuals ask how a cell's expression would change under altered spatial neighbor contexts. Such queries are central to predicting cell behavior in tissues, but lack a unified definition, with existing methods targeting specific intervention types or treating cells as i.i.d. In this work, we first formalize tissue graph counterfactuals as a class of spatial interventions that either rewire connections between cells (edge perturbation) or modify the expression of their neighbors (node perturbation). We then introduce Cellina (https://cellina.readthedocs.io) - a framework that uses supervised disentanglement to decompose a cell's intrinsic state from its spatial context, using the latter as a conditioning input for counterfactual predictions. Across benchmarks spanning over 2.5 million spatially-resolved cells in colorectal cancer and mouse brain, Cellina outperforms spatially-informed and non-spatial competitors in in-silico graph perturbations, disentanglement, and scalability. Additionally, we show that Cellina reveals biologically distinct cancer subdomains in an unsupervised manner and enables targeted neighbor perturbation simulations.

q-bio.GN

Adversarial Distribution Balancing for Counterfactual Reasoning

The development of causal prediction models is challenged by the fact that the outcome is only observable for the applied (factual) intervention and not for its alternatives (the so-called counterfactuals); in medicine we only know patients' survival for the administered drug and not for other therapeutic options. Machine learning approaches for counterfactual reasoning have to deal with both unobserved outcomes and distributional differences due to non-random treatment administration. Unsupervised domain adaptation (UDA) addresses similar issues; one has to deal with unobserved outcomes -- the labels of the target domain -- and distributional differences between source and target domain. We propose Adversarial Distribution Balancing for Counterfactual Reasoning (ADBCR), which directly uses potential outcome estimates of the counterfactuals to remove spurious causal relations. We show that ADBCR outcompetes state-of-the-art methods on three benchmark datasets, and demonstrate that ADBCR's performance can be further improved if unlabeled validation data are included in the training procedure to better adapt the model to the validation domain.

cs.LG

FACT: Federated Adversarial Cross Training

Federated Learning (FL) facilitates distributed model development to aggregate multiple confidential data sources. The information transfer among clients can be compromised by distributional differences, i.e., by non-i.i.d. data. A particularly challenging scenario is the federated model adaptation to a target client without access to annotated data. We propose Federated Adversarial Cross Training (FACT), which uses the implicit domain differences between source clients to identify domain shifts in the target domain. In each round of FL, FACT cross initializes a pair of source clients to generate domain specialized representations which are then used as a direct adversary to learn a domain invariant data representation. We empirically show that FACT outperforms state-of-the-art federated, non-federated and source-free domain adaptation models on three popular multi-source-single-target benchmarks, and state-of-the-art Unsupervised Domain Adaptation (UDA) models on single-source-single-target experiments. We further study FACT's behavior with respect to communication restrictions and the number of participating clients.

cs.LG

BITES: Balanced Individual Treatment Effect for Survival data

Estimating the effects of interventions on patient outcome is one of the key aspects of personalized medicine. Their inference is often challenged by the fact that the training data comprises only the outcome for the administered treatment, and not for alternative treatments (the so-called counterfactual outcomes). Several methods were suggested for this scenario based on observational data, i.e.~data where the intervention was not applied randomly, for both continuous and binary outcome variables. However, patient outcome is often recorded in terms of time-to-event data, comprising right-censored event times if an event does not occur within the observation period. Albeit their enormous importance, time-to-event data is rarely used for treatment optimization. We suggest an approach named BITES (Balanced Individual Treatment Effect for Survival data), which combines a treatment-specific semi-parametric Cox loss with a treatment-balanced deep neural network; i.e.~we regularize differences between treated and non-treated patients using Integral Probability Metrics (IPM). We show in simulation studies that this approach outperforms the state of the art. Further, we demonstrate in an application to a cohort of breast cancer patients that hormone treatment can be optimized based on six routine parameters. We successfully validated this finding in an independent cohort. BITES is provided as an easy-to-use python implementation.

stat.ME