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. 2021 Aug 16;11:16605. doi: 10.1038/s41598-021-95747-4

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© The Author(s) 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Overview of modeling approaches and inference. Overview of the histologic-subtype approach (top) and the weakly supervised approach (bottom). In the histologic-subtype approach, feature maps of histologic patterns produced by LungCNN-Histo in stage 1 and are combined with clinical features to predict TMB-status in stage 2. The weakly supervised approach also utilizes a two stage approach, whereby a weakly supervised model (WS-S1) is developed to produce patch-level TMB predictions at inference. The patch-level data are aggregated over the entire tissue area in stage 1 and combined with clinical features to provide TMB classification in stage 2.