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. Author manuscript; available in PMC: 2021 Mar 25.
Published in final edited form as: Cell Syst. 2020 Mar 4;10(3):265–274.e11. doi: 10.1016/j.cels.2020.02.003

Figure 3: Scribe recovers a core regulatory network responsible for myelopoiesis.

Figure 3:

(A) A core network describes key regulators during the specification of monocytes and granulocytes (Olsson et al., 2016). (B) Examples of gene-target pair kinetic curves over pseudotime along the monocyte lineage. (C) Scribe infers the expected core regulatory network interactions for myelopoiesis. (D) Visualization of combinatorial gene regulation from Irf8 and Gfi1 to Zeb2 or Per3. (E) The normalized rank of lineage-specific genes’ total outgoing RDI sum. (F) Lineage-specific network of significant regulators during erythropoiesis. Edges supported by the SPRING database are colored as red lines. For panels E (F), BEAM analysis was used to identify significant branching genes associated with the four (one) lineage bifurcation events shown in the haematopoietic trajectory from ref. (Qiu et al., 2017a) based on the paul dataset (Paul et al., 2015). The top 1,000 differentially expressed genes associated with each bifurcation were chosen to build a causal network for each relevant lineage. A set of TFs relevant to specific lineages described previously is used for panel E or F. Neu: Neutrophil; Ery: Erythroid, Mk: Megakaryocyte; Mono: Monocyte; DC: Dendritic Cell; BE: Basophil / Eosinophil. (G, H) Receiver Operating Curves or ROC (G, top) and Area Under Curve or AUC (H, bottom) of the inferred causal network based on Scribe, GC and CCM, from left to right, on the Dendritic Cells (DC) dataset, the granulocyte or monocyte branch of the Olsson dataset, the erythroid branch of the Paul dataset. Four different variants of causal inference implemented in Scribe are tested: RDI ( L = 0): the default RDI method without conditioning on any other gene; RDI (L = 1): the RDI method based on conditioning on the incoming gene with highest causality score, except the current target; uRDI: the method based on the uniformization technique applied on the actual distribution in RDI; uRDI ( L = 1): the uRDI method but also with the conditioning on the incoming gene with the highest causality score, except the current target. (I) The network of the gene-set as included in the panel (panel F) retrieved from the STRING database.