Protein Fitness Landscape

Overview

This tool visualizes protein fitness landscapes and epistatic interactions between amino acid positions in PAM sequences. The data is based on published experimental data and models from the paper:

Citation:
"Custom CRISPR–Cas9 PAM variants via scalable engineering and machine learning"
Nature (2025)
DOI: 10.1038/s41586-025-09021-y

Controls

• Position A/B: Select two amino acid positions to compare
• Metric: Choose which PAM sequence to analyze (Max shows the maximum across all PAMs)
• Mode: Toggle between Landscape (3D surface) and Interaction (epistatic analysis) views

Visualization Modes

Landscape Mode: Shows a 3D surface plot of fitness values for all amino acid combinations at the selected positions. The orange diamond marks the wild-type variant.

Interaction Mode: Displays epistatic coefficients as a heatmap alongside a scatter plot comparing observed vs. predicted additive effects. R² indicates how well mutations combine additively.

Interacting with Plots

• Click and drag to rotate 3D plots
• Scroll to zoom in/out
• Double-click to reset view
• Hover over data points for details

Export & Share

Use the export buttons to save plots as PNG or SVG files. The share link button copies a URL with your current settings that you can share with colleagues.