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Table 1.

Ethanol-metabolizing genes of interest (n = 11), with annotation indicating whether they were present in the gnomAD gene constraints file (10), in the mouse brain expression set (1), and in the invertebrate set (5).

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Table 2.

Correlations between the gene metrics from the gnomAD database.

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Table 2 Expand

Fig 1.

(a) Flow diagram with gene counts for the human GOI set, the mouse expression set, and the invertebrate set, through filtering and combination for hypothesis testing sets, and (b) Venn diagram illustrating the overlap of genes in the sets of interest, after filtering for presence in gnomAD. (Figure created with BioRender.com).

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Fig 1 Expand

Fig 2.

Example gene clusters plotted to show three of the 10 clustering gene metrics, SYN z-score, transcript length, and pLI.

The 4 clusters in orange, green, blue, and pink represent actual gene clusters from the data, while the genes in gray represent a random selection of genes.

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Fig 2 Expand

Fig 3.

Flow chart demonstrating the analysis framework.

(Figure created with BioRender.com).

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Fig 3 Expand

Fig 4.

Example of one branch (cluster of interest) from the final, pruned hierarchical clustering tree.

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Fig 5.

Relationship between median number of genes per cluster of interest and proportion of the exome included in the cluster of interest.

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Fig 5 Expand

Table 3.

For each of the three GOI test sets, median cluster size (Med. Size), number of total genes, combined across all clusters of interest (No.Genes), and proportion of the exome retained in the clusters of interest (Prop. Gen) for hierarchical clustering trees cut at various heights.

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Fig 6.

Simulation estimates of parameter values with standard deviations and true simulated values.

One standard deviation from the point estimate is shown in the same color as the plotted point with one additional standard deviation shown in gray. The starred point shows the true, simulated point value. Estimates shown for (a) LOF, (b) MIS, and (c) SYN variants.

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Fig 6 Expand

Table 4.

Logistic regression results.

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Table 4 Expand