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. 2021 Aug 13;10:e66417. doi: 10.7554/eLife.66417

Figure 5. Genes and pathways induced in the SARS-CoV-2-infected lung organoid monolayers (disease model) are induced also in the lungs of COVID-19 patients (actual disease).

(A–C) Adult lung organoid monolayers infected or not with SARS-CoV-2 were analyzed by RNA seq and differential expression analysis. Differentially expressed genes (DEGs; B) are displayed as a heatmap in (C). While only selected genes are labeled in panel (C) (which represent overlapping DEGs between our organoid model and publicly available COVID-19 lung dataset, GSE151764), the same heatmap is presented in Figure 5—figure supplement 1 with all genes labeled. (D) Reactome-pathway analysis shows the major pathways upregulated in SARS-CoV-2-infected lung organoid monolayers. See also Figure 5—figure supplement 2 for visualization as hierarchical ReacFoam. (E) A Venn diagram showing overlaps in DEGs between model (current work; B) and disease (COVID-19 lung dataset, GSE151764; Figure 4). (F) Bar plots display the ability of the DEGs in infected lung monolayers to classify human normal vs. COVID-19 respiratory samples from five independent cohorts. (G–I) Bar (top) and violin (bottom) plots compare the accuracy of disease modeling in three publicly available human lung datasets, as determined by the significant induction of the DEGs that were identified in the SARS-CoV-2-challenged monolayers. See also Table 6, which enlists details regarding the patient cohorts/tissue or cell types represented in each transcriptomic dataset.

Figure 5.

Figure 5—figure supplement 1. Differential expression analysis of RNA seq datasets from adult lung organoid monolayers, infected or not, with SARS-CoV-2.

Figure 5—figure supplement 1.

Adult lung organoid (ALO)-derived grown in transwells as submerged monolayers were infected or not with SARS-CoV-2 were analyzed by RNA seq and differential expression analysis. Differentially expressed genes are displayed as a heatmap.
Figure 5—figure supplement 2. Reactome-pathway analysis of differentially expressed genes in lung organoid monolayers infected with SARS-CoV-2.

Figure 5—figure supplement 2.

Reactome-pathway analysis of the differentially expressed genes shows the major pathways upregulated in SARS-CoV-2-infected lung organoid monolayers. Top: visualization as flattened (left) and hierarchical (right, insets) ReacFoam. Bottom: visualization of the same data as tables with statistical analysis indicative of the degree of pathway enrichment.
Figure 5—figure supplement 3. Head-to-head comparison of our adult lung organoid (ALO)-derived model of COVID-19 versus another lung organoid model in their ability to recapitulate the differentially expressed genes (DEGs) observed in lung tissues from fatal cases of COVID-19.

Figure 5—figure supplement 3.

(A) Venn diagrams show the number of overlapping and nonoverlapping DEGs (both up- and downregulated genes) between our organoid model and four human COVID-19 patient-derived samples (left). GSE151764 represents postmortem COVID-19 and normal lung tissues; GSE156063 represents upper airway samples from patients with COVID-19; GSE145926 represents sorted epithelial population from bronchoalveolar lavage fluid (BALF) derived from patients with varying severity of COVID-19; GSE157526 represents tracheal-bronchial cells infected with SARS-Cov2. (B) Venn diagrams as in (A), comparing a publicly available SARS-Cov2-infected human lung organoid model (GSE160435) and the same four human COVID-19 respiratory cohorts as in (A). (C) Venn diagrams show the DEGs between our organoid model and the publicly available lung organoid model. The comparison was carried out by calculating the percentage of the common up/down DEGs represented within the total up/down DEG for the two models in each Venn diagram.