{"about":{"site":"https://codewithpapers.app","non_affiliation":"Code with Papers and Syntology are not affiliated with, endorsed by, or sponsored by Papers with Code, Meta, or the pwc-archive mirror.","licence":"CC BY-SA 4.0","licence_url":"https://creativecommons.org/licenses/by-sa/4.0/legalcode","attribution":"https://codewithpapers.app/attribution","modified":"archive material modified by Syntology; see the attribution page"},"url":"/paper/causal-integration-of-chemical-structures","title":"Causal integration of chemical structures improves representations of microscopy images for morphological profiling","arxiv_id":"2504.09544","date":"2025-04-13","proceeding":null,"authors":["Yemin Yu","Neil Tenenholtz","Lester Mackey","Ying WEI","David Alvarez-Melis","Ava P. Amini","Alex X. Lu"],"abstract":"Recent advances in self-supervised deep learning have improved our ability to quantify cellular morphological changes in high-throughput microscopy screens, a process known as morphological profiling. However, most current methods only learn from images, despite many screens being inherently multimodal, as they involve both a chemical or genetic perturbation as well as an image-based readout. We hypothesized that incorporating chemical compound structure during self-supervised pre-training could improve learned representations of images in high-throughput microscopy screens. We introduce a representation learning framework, MICON (Molecular-Image Contrastive Learning), that models chemical compounds as treatments that induce counterfactual transformations of cell phenotypes. MICON significantly outperforms classical hand-crafted features such as CellProfiler and existing deep-learning-based representation learning methods in challenging evaluation settings where models must identify reproducible effects of drugs across independent replicates and data-generating centers. We demonstrate that incorporating chemical compound information into the learning process provides consistent improvements in our evaluation setting and that modeling compounds specifically as treatments in a causal framework outperforms approaches that directly align images and compounds in a single representation space. Our findings point to a new direction for representation learning in morphological profiling, suggesting that methods should explicitly account for the multimodal nature of microscopy screening data.","url_abs":"https://arxiv.org/abs/2504.09544v2","url_pdf":"https://arxiv.org/pdf/2504.09544v2.pdf","source":{"archive":"pwc-archive (Hugging Face), CC BY-SA 4.0","snapshot":"2025-07-28","licence_url":"https://creativecommons.org/licenses/by-sa/4.0/legalcode","row_kind":"abstracts"},"code_links":[{"paper_slug":"causal-integration-of-chemical-structures","repo_url":"https://github.com/microsoft/micon","is_official":1,"mentioned_in_paper":1,"mentioned_in_github":0,"framework":"pytorch","reach":null}],"tasks":[{"task_slug":"contrastive-learning","task_name":"Contrastive Learning"},{"task_slug":"representation-learning","task_name":"Representation Learning"},{"task_slug":null,"task_name":"counterfactual"}],"methods":[{"method_slug":"align","method_name":"ALIGN"}],"datasets_introduced":[],"methods_introduced":[],"results":[],"syntology":{"atlas_url":"https://app.syntology.ai/?focus=2504.09544","mcp":null,"developers":"https://syntology.ai/developers"},"arxiv_metadata":null,"syntology_extracted_results":null}