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. 2021 Jul 27;12:4563. doi: 10.1038/s41467-021-24814-1

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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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 3 — a Genes were classified into three different categories based on NF54-expression with and without HS-exposure across all three parasite lines (Supplementary Data File 3, “Methods” section): upregulated in HS (↑, n = 415), downregulated in HS (↓, n = 611), or not regulated by HS (⎯, n = 1541). Genes expressed above threshold in NF54 and both HS-Sensitive mutants (n = 1298) were then assigned into six HS expression categories based on phenotype in NF54 vs. mutants ΔLRR5 and ΔDHC. HS-regulated genes shared between NF54 and both mutants are indicated in red (↑↑↑, n = 94) or blue (↓↓↓, n = 205) for upregulated and downregulated genes, respectively. Genes dysregulated in one or both HS-Sensitive mutants fell into two main expression-profile categories: those upregulated in NF54 that failed to be regulated in the mutants (↑⤯⤯, n = 83), and genes not regulated in response to HS in NF54 that were inappropriately upregulated in the mutants (⎯ ↑↑, n = 74). Most remaining genes were not regulated in response to HS in any parasite line (n = 615). b Functional enrichment analyses between wild-type/mutant HS-expression profiles. Red: Shared upregulated HS-responsive GO-terms between NF54 and the two HS-Sensitive pB-mutants (↑↑↑). Blue: Shared downregulated GO-terms (↓↓↓). Ocher: GO-terms upregulated in NF54 but dysregulated in both mutants (↑⤯⤯). Tan: GO-terms enriched in genes not regulated in the wild-type HS-response but upregulated in the mutants (⎯ ↑↑). Only enriched GO-terms are shown (two-tailed Fisher/elim-hybrid test p-value ≤ 0.05), with the highest significance indicated in dark green. Fraction of significant genes mapping to a GO-term in an HS expression-profile category vs. genes mapping to that GO-term in the entire analysis is indicated by distance to the center of the circle. Source data are provided as a Source Data file. c Several apicoplasts and isoprenoid biosynthesis-related genes were upregulated in the wild-type response to HS and were dysregulated in one or both HS-Sensitive pB-mutant clones (↑⤯⤯). *Isoprenoid biosynthesis-related genes upregulated by HS confirmed in the pooled HS-Screen.