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Real-world deployment of computer vision systems, including in the discovery processes of biomedical research, requires causal representations that are invariant to contextual nuisances and generalize to new data. Leveraging the internal replicate structure of two novel single-cell fluorescent microscopy datasets, we propose generally applicable tests to assess the extent to which models learn causal representations across increasingly challenging levels of OODgeneralization. We show that despite seemingly strong performance as assessed by other established metrics, both naive and contemporary baselines designed to ward against confounding, collapse to random on these tests. We introduce a new method, Interventional Style Transfer (IST), that substantially improves OOD generalization by generating interventional training distributions in which spurious correlations between biological causes and nuisances are mitigated. We publish our code and datasets. 

Abstract MotivationHigh-quality curation of the proteins and interactions in signaling pathways is slow and painstaking. As a result, many experimentally detected interactions are not annotated to any pathways. A natural question that arises is whether or not it is possible to automatically leverage existing pathway annotations to identify new interactions for inclusion in a given pathway. ResultsWe present RegLinker, an algorithm that achieves this purpose by computing multiple short paths from pathway receptors to transcription factors within a background interaction network. The key idea underlying RegLinker is the use of regular language constraints to control the number of non-pathway interactions that are present in the computed paths. We systematically evaluate RegLinker and five alternative approaches against a comprehensive set of 15 signaling pathways and demonstrate that RegLinker recovers withheld pathway proteins and interactions with the best precision and recall. We used RegLinker to propose new extensions to the pathways. We discuss the literature that supports the inclusion of these proteins in the pathways. These results show the broad potential of automated analysis to attenuate difficulties of traditional manual inquiry. Availability and implementationhttps://github.com/Murali-group/RegLinker. Supplementary informationSupplementary data are available at Bioinformatics online.