MOSBY enables multi-omic inference and spatial biomarker discovery from whole slide images

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Bibliografske podrobnosti
izdano v:Scientific Reports (Nature Publisher Group) vol. 14, no. 1 (2024), p. 18271
Glavni avtor: Şenbabaoğlu, Yasin
Drugi avtorji: Prabhakar, Vignesh, Khormali, Aminollah, Eastham, Jeff, Liu, Evan, Warner, Elisa, Nabet, Barzin, Srivastava, Minu, Ballinger, Marcus, Liu, Kai
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Nature Publishing Group
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022 |a 2045-2322 
024 7 |a 10.1038/s41598-024-69198-6  |2 doi 
035 |a 3089709561 
045 2 |b d20240101  |b d20241231 
084 |a 274855  |2 nlm 
100 1 |a Şenbabaoğlu, Yasin  |u Genentech, Inc., South San Francisco, USA (ISNI:0000 0004 5899 3818) 
245 1 |a MOSBY enables multi-omic inference and spatial biomarker discovery from whole slide images 
260 |b Nature Publishing Group  |c 2024 
513 |a Journal Article 
520 3 |a The utility of deep neural nets has been demonstrated for mapping hematoxylin-and-eosin (H&E) stained image features to expression of individual genes. However, these models have not been employed to discover clinically relevant spatial biomarkers. Here we develop MOSBY (Multi-Omic translation of whole slide images for Spatial Biomarker discoverY) that leverages contrastive self-supervised pretraining to extract improved H&E whole slide images features, learns a mapping between image and bulk omic profiles (RNA, DNA, and protein), and utilizes tile-level information to discover spatial biomarkers. We validate MOSBY gene and gene set predictions with spatial transcriptomic and serially-sectioned CD8 IHC image data. We demonstrate that MOSBY-inferred colocalization features have survival-predictive power orthogonal to gene expression, and enable concordance indices highly competitive with survival-trained multimodal networks. We identify and validate (1) an ER stress-associated colocalization feature as a chemotherapy-specific risk factor in lung adenocarcinoma, and (2) the colocalization of T effector cell vs cysteine signatures as a negative prognostic factor in multiple cancer indications. The discovery of clinically relevant biologically interpretable spatial biomarkers showcases the utility of the model in unraveling novel insights in cancer biology as well as informing clinical decision-making. 
653 |a Peptide mapping 
653 |a Lung cancer 
653 |a Biomarkers 
653 |a Gene mapping 
653 |a Risk factors 
653 |a Adenocarcinoma 
653 |a Gene expression 
653 |a Transcriptomics 
653 |a Information processing 
653 |a Chemotherapy 
653 |a CD8 antigen 
653 |a Decision making 
653 |a Environmental 
700 1 |a Prabhakar, Vignesh  |u Genentech, Inc., South San Francisco, USA (ISNI:0000 0004 5899 3818) 
700 1 |a Khormali, Aminollah  |u Genentech, Inc., South San Francisco, USA (ISNI:0000 0004 5899 3818) 
700 1 |a Eastham, Jeff  |u Genentech, Inc., South San Francisco, USA (ISNI:0000 0004 5899 3818) 
700 1 |a Liu, Evan  |u Genentech, Inc., South San Francisco, USA (ISNI:0000 0004 5899 3818) 
700 1 |a Warner, Elisa  |u Genentech, Inc., South San Francisco, USA (ISNI:0000 0004 5899 3818) 
700 1 |a Nabet, Barzin  |u Genentech, Inc., South San Francisco, USA (ISNI:0000 0004 5899 3818) 
700 1 |a Srivastava, Minu  |u Genentech, Inc., South San Francisco, USA (ISNI:0000 0004 5899 3818) 
700 1 |a Ballinger, Marcus  |u Genentech, Inc., South San Francisco, USA (ISNI:0000 0004 5899 3818) 
700 1 |a Liu, Kai  |u Genentech, Inc., South San Francisco, USA (ISNI:0000 0004 5899 3818) 
773 0 |t Scientific Reports (Nature Publisher Group)  |g vol. 14, no. 1 (2024), p. 18271 
786 0 |d ProQuest  |t Science Database 
856 4 1 |3 Citation/Abstract  |u https://www.proquest.com/docview/3089709561/abstract/embedded/7BTGNMKEMPT1V9Z2?source=fedsrch 
856 4 0 |3 Full Text - PDF  |u https://www.proquest.com/docview/3089709561/fulltextPDF/embedded/7BTGNMKEMPT1V9Z2?source=fedsrch