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. 2023 Feb 8;614(7949):742–751. doi: 10.1038/s41586-022-05688-9

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© The Author(s), under exclusive licence to Springer Nature Limited 2023

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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Extended Data Fig. 4 — (a—d) Schematic for perturbation score (PS) calculation. CellOracle calculates a PS by comparing the direction of the simulated cell state transition with the direction of cell differentiation. (a) Schematic for differentiation vector calculations. First, the pseudotime data are summarized by grid points. Then, CellOracle calculates a 2D gradient vector of the pseudotime data representing the directionality of differentiation pseudotime. (b) Calculation of the inner-product value between the differentiation vector and gene perturbation vectors. First, the results of the perturbation simulation are converted into the same vector field format as the differentiation vector field, and the inner product of these vectors is calculated to produce a PS. (c) A positive PS (magenta) suggests the perturbation vector and differentiation vector share a similar direction, thus, suggesting the TF perturbation would promote differentiation. In contrast, a negative PS (green) represents inhibited differentiation. (d) Schematic for perturbation score interpretation. A positive perturbation score (green) predicts that the perturbation promotes differentiation. A negative perturbation score (purple) represents inhibited differentiation.