A model of CRX and NRL-driven cis-regulatory activity in Crx^-/- retina.

(A) The performance of different model architectures measured by Pearson correlation coefficients, wild-type retina. (B) Estimates of model parameter uncertainties for additive (left) and pairwise interaction (right) parameters, generated by the built-in MAVE-NN function to estimate uncertainties. Interaction parameters are ordered by rank for visualization. (C) Model parameters for position-specific pairwise contributions of CRX and NRL sites in wild-type retina. Forward and reverse orientation of binding sites is indicated by capital or lower case letter. CRX sites are either high (C or c), medium (M or m), or low (L or l) affinity. NRL sites are labeled N or n and the Rho promoter is labeled R. There are no model parameters for Hsp68 (H, used as the overall basal sequence) or the placeholder site _ used to equalize the lengths of input sequences. See methods for details. (D) Anomalous activity of reverse medium affinity CRX site, compared to the forward site. Additive parameters shown for independently trained pairwise models initialized from different random seeds (n = 8). (E, F) Performance of different model architectures fit to MPRA measurements of the CRX-NRL library in Crx^-/- retina. (G) Estimates of model parameter uncertainties for additive (left) and pairwise interaction (right) parameters in Crx^-/- retina. (H) Observed activity (y-axis) of test set sequences vs the latent phenotype inferred by the pairwise model of Crx^-/- retina. (I) Observed activity (y-axis) of test set sequences vs predicted activity of the pairwise model of Crx^-/- retina. (J) Position-specific pairwise contributions of CRX and NRL sites to activity in Crx^-/- retina.

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