Sangam: A Confluence of Knowledge Streams

Self-supervised learning of cell type specificity from immunohistochemical images

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dc.contributor Massachusetts Institute of Technology. Department of Biological Engineering
dc.creator Murphy, Michael
dc.creator Jegelka, Stefanie
dc.creator Fraenkel, Ernest
dc.date 2023-01-31T19:11:55Z
dc.date 2023-01-31T19:11:55Z
dc.date 2022-06-24
dc.date 2023-01-31T18:58:14Z
dc.date.accessioned 2023-02-17T20:27:46Z
dc.date.available 2023-02-17T20:27:46Z
dc.identifier https://hdl.handle.net/1721.1/147819
dc.identifier Murphy, Michael, Jegelka, Stefanie and Fraenkel, Ernest. 2022. "Self-supervised learning of cell type specificity from immunohistochemical images." Bioinformatics, 38 (Supplement_1).
dc.identifier.uri http://localhost:8080/xmlui/handle/CUHPOERS/242588
dc.description <jats:title>Abstract</jats:title> <jats:sec> <jats:title>Motivation</jats:title> <jats:p>Advances in bioimaging now permit in situ proteomic characterization of cell–cell interactions in complex tissues, with important applications across a spectrum of biological problems from development to disease. These methods depend on selection of antibodies targeting proteins that are expressed specifically in particular cell types. Candidate marker proteins are often identified from single-cell transcriptomic data, with variable rates of success, in part due to divergence between expression levels of proteins and the genes that encode them. In principle, marker identification could be improved by using existing databases of immunohistochemistry for thousands of antibodies in human tissue, such as the Human Protein Atlas. However, these data lack detailed annotations of the types of cells in each image.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>We develop a method to predict cell type specificity of protein markers from unlabeled images. We train a convolutional neural network with a self-supervised objective to generate embeddings of the images. Using non-linear dimensionality reduction, we observe that the model clusters images according to cell types and anatomical regions for which the stained proteins are specific. We then use estimates of cell type specificity derived from an independent single-cell transcriptomics dataset to train an image classifier, without requiring any human labelling of images. Our scheme demonstrates superior classification of known proteomic markers in kidney compared to selection via single-cell transcriptomics.</jats:p> </jats:sec> <jats:sec> <jats:title>Availability and implementation</jats:title> <jats:p>Code and trained model are available at www.github.com/murphy17/HPA-SimCLR.</jats:p> </jats:sec> <jats:sec> <jats:title>Supplementary information</jats:title> <jats:p>Supplementary data are available at Bioinformatics online.</jats:p> </jats:sec>
dc.format application/pdf
dc.language en
dc.publisher Oxford University Press (OUP)
dc.relation 10.1093/bioinformatics/btac263
dc.relation Bioinformatics
dc.rights Creative Commons Attribution 4.0 International license
dc.rights https://creativecommons.org/licenses/by/4.0/
dc.source Oxford University Press
dc.title Self-supervised learning of cell type specificity from immunohistochemical images
dc.type Article
dc.type http://purl.org/eprint/type/JournalArticle


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