Fig. 6: Mutagenesis of puncta(+) expressed FOs. | Nature Communications

Fig. 6: Mutagenesis of puncta(+) expressed FOs.

From: Defining the condensate landscape of fusion oncoproteins

Fig. 6

a SHapley Additive exPlanations (SHAP) (top) and feature value (bottom) analysis for unmutated (orange) and mutated (purple shades) FOs. Positive SHAP contribution values indicate the magnitude of contributions to puncta(+) predictions, while negative SHAP contribution values indicate the magnitude of contributions to puncta(-) predictions. The five features with the largest SHAP contributions based on absolute values are listed for each FO and those used in mutant design are highlighted in gray. See Figure S6 and Supplementary Dataset 7 for the full complement of features and values for all eight FOs that were mutated. See Supplementary Dataset 5 for additional information on the physicochemical features used in these analyses. b The top three amino acid enrichments or depletions within the intrinsically disordered regions (IDRs) of the specified unmutated (orange) and mutated (purple shades) FOs. Those used in mutant design are highlighted in gray. See Figure S6 and Supplementary Dataset 7 for the full complement of IDR amino acid enrichments or depletions for the eight FOs that were mutated. c Plot of the FO-puncta ML model condensation probability prediction on the y-axis and experimentally determined percentage of puncta(+) cells on the x-axis. Unmutated FOs are in orange. Mutated FOs that were correctly predicted as puncta(-) are in purple. Mutant FOs that were puncta(+) are in gray. Lines connect unmutated FOs to their mutated counterparts and are color-coded based on the group (Group 1–4) from which the original FO was derived. FO names are indicated along the lines. The FO-Puncta ML model cut-off for puncta(-) classification is less than 0.83. The experimental puncta(-) cut-off is less than 17% of cells with puncta. See Fig. S7 for representative cell images of each unmutated and mutated FO. All source data are provided as a Source Data File.

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