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. 2024 Jan 9;16:8. doi: 10.1186/s13073-023-01279-z

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© The Author(s) 2024

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/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 1 — A Pan-cancer analysis of transformation state from pan-tissue single-cell reference atlases. Fit quality and embryonic signal of bulk transcriptomes with increasingly complete reference atlases: Fractional contribution of embryonic reference (y-axis, early embryo + gastrulation for full reference, early embryo otherwise) in explaining bulk transcriptomes (dots) as a function of goodness of fit (x-axis, pseudo R-squared) when fit using single cell reference consisting of cells from the early embryo (yellow), early embryo and gastrulation (dark red), or early embryo, gastrulation, foetal, and mature pan-tissue reference (green). Bulk cancer transcriptomes are circled in black and genuinely embryonal controls (blastoids) are circled in grey. B Relative contribution of references to explaining the bulk transcriptomes of a range of adult and childhood cancers: Average relative contribution of early embryo (yellow), gastrulation (dark red), foetal (purple), and adult (green) single cell reference populations in explaining bulk transcriptomes (y-axis) for different combinations of these references (x-axis, labels at top). Bulk transcriptomes are organised by source (labels on the right). C Childhood cancers have a stronger foetal contribution than adult cancers or control populations: Relative contribution of foetal reference (y-axis) in explaining bulk cancer transcriptomes (dots), when provided a complete set of the early embryo, gastrulation, foetal, and adult single-cell references. Bulk transcriptomes are split into childhood (purple), adult (green), and blastoid control (orange) and then by cancer type (x-axis). Distributions are summarised by median (horizontal lines), 1st and 3rd quartiles (horizontal lines for cancer types, shaded coloured areas for childhood/adult/control), and 1.5 times inter-quartile range (light-shaded areas)