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Update app.py
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app.py
CHANGED
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@@ -1,5 +1,6 @@
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import gradio as gr
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import torch
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import numpy as np
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from itertools import product
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import torch.nn as nn
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@@ -7,7 +8,6 @@ import matplotlib.pyplot as plt
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import matplotlib.colors as mcolors
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import io
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from PIL import Image
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from scipy.interpolate import interp1d
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###############################################################################
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# 1. MODEL DEFINITION
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@@ -71,7 +71,7 @@ def sequence_to_kmer_vector(sequence: str, k: int = 4) -> np.ndarray:
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total_kmers = len(sequence) - k + 1
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if total_kmers > 0:
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vec
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return vec
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@@ -86,10 +86,12 @@ def calculate_shap_values(model, x_tensor):
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"""
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model.eval()
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with torch.no_grad():
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baseline_output = model(x_tensor)
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baseline_probs = torch.softmax(baseline_output, dim=1)
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baseline_prob = baseline_probs[0, 1].item() # Probability of 'human'
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shap_values = []
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x_zeroed = x_tensor.clone()
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for i in range(x_tensor.shape[1]):
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@@ -100,7 +102,7 @@ def calculate_shap_values(model, x_tensor):
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prob = probs[0, 1].item()
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impact = baseline_prob - prob
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shap_values.append(impact)
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x_zeroed[0, i] = original_val
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return np.array(shap_values), baseline_prob
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###############################################################################
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@@ -108,6 +110,10 @@ def calculate_shap_values(model, x_tensor):
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###############################################################################
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def compute_positionwise_scores(sequence, shap_values, k=4):
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kmers = [''.join(p) for p in product("ACGT", repeat=k)]
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kmer_dict = {km: i for i, km in enumerate(kmers)}
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@@ -132,13 +138,20 @@ def compute_positionwise_scores(sequence, shap_values, k=4):
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###############################################################################
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def find_extreme_subregion(shap_means, window_size=500, mode="max"):
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n = len(shap_means)
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if n == 0:
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return (0, 0, 0.0)
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if window_size >= n:
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avg_val = float(np.mean(shap_means))
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return (0, n, avg_val)
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csum = np.zeros(n + 1, dtype=np.float32)
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csum[1:] = np.cumsum(shap_means)
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@@ -165,6 +178,7 @@ def find_extreme_subregion(shap_means, window_size=500, mode="max"):
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###############################################################################
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def fig_to_image(fig):
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buf = io.BytesIO()
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fig.savefig(buf, format='png', bbox_inches='tight', dpi=150)
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buf.seek(0)
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@@ -173,14 +187,27 @@ def fig_to_image(fig):
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return img
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def get_zero_centered_cmap():
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colors = [
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(0.0, 'blue'),
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(0.5, 'white'),
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(1.0, 'red')
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]
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def plot_linear_heatmap(shap_means, title="Per-base SHAP Heatmap", start=None, end=None):
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if start is not None and end is not None:
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local_shap = shap_means[start:end]
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subtitle = f" (positions {start}-{end})"
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@@ -191,46 +218,73 @@ def plot_linear_heatmap(shap_means, title="Per-base SHAP Heatmap", start=None, e
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if len(local_shap) == 0:
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local_shap = np.array([0.0])
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heatmap_data = local_shap.reshape(1, -1)
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min_val = np.min(local_shap)
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max_val = np.max(local_shap)
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extent = max(abs(min_val), abs(max_val))
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cmap = get_zero_centered_cmap()
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cax = ax.imshow(
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heatmap_data,
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aspect='auto',
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cmap=
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vmin=-extent,
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vmax
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)
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cbar = plt.colorbar(
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cax,
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orientation='horizontal',
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pad=0.25,
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aspect=40,
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shrink=0.8
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)
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cbar.ax.tick_params(labelsize=8)
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cbar.set_label('SHAP Contribution', fontsize=9, labelpad=5)
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ax.set_yticks([])
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ax.set_xlabel('Position in Sequence', fontsize=10)
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ax.set_title(f"{title}{subtitle}", pad=10)
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return fig
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def create_importance_bar_plot(shap_values, kmers, top_k=10):
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plt.rcParams.update({'font.size': 10})
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fig = plt.figure(figsize=(10, 5))
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indices = np.argsort(np.abs(shap_values))[-top_k:]
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values = shap_values[indices]
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features = [kmers[i] for i in indices]
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colors = ['#99ccff' if v < 0 else '#ff9999' for v in values]
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plt.barh(range(len(values)), values, color=colors)
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plt.yticks(range(len(values)), features)
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plt.xlabel('SHAP Value (impact on model output)')
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@@ -240,6 +294,9 @@ def create_importance_bar_plot(shap_values, kmers, top_k=10):
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return fig
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def plot_shap_histogram(shap_array, title="SHAP Distribution in Region"):
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fig, ax = plt.subplots(figsize=(6, 4))
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ax.hist(shap_array, bins=30, color='gray', edgecolor='black')
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ax.axvline(0, color='red', linestyle='--', label='0.0')
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@@ -251,102 +308,119 @@ def plot_shap_histogram(shap_array, title="SHAP Distribution in Region"):
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return fig
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def compute_gc_content(sequence):
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if not sequence:
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return 0
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gc_count = sequence.count('G') + sequence.count('C')
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return (gc_count / len(sequence)) * 100.0
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###############################################################################
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# 7.
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###############################################################################
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device = torch.device("cuda" if torch.cuda.is_available() else "cpu")
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model = VirusClassifier(256)
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model.load_state_dict(torch.load("model.pt", map_location=device))
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model.to(device)
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model.eval()
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KMERS_4 = [''.join(p) for p in product("ACGT", repeat=4)]
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def analyze_sequence(file_path, top_k=10, fasta_text="", window_size=500):
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"""
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"""
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try:
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if not fasta_text.strip():
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return ("Error: No sequence provided", None, None, {}, "")
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sequences = parse_fasta(fasta_text)
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if not sequences:
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return ("Error: No valid FASTA sequences found", None, None, {}, "")
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header, sequence = sequences[0]
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x = sequence_to_kmer_vector(sequence, k=4)
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x_tensor = torch.tensor(x).float().unsqueeze(0).to(device)
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with torch.no_grad():
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output = model(x_tensor)
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probs = torch.softmax(output, dim=1)
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pred_human = probs[0, 1].item()
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classification = "Human" if pred_human > 0.5 else "Non-human"
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shap_values, baseline_prob = calculate_shap_values(model, x_tensor)
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shap_means = compute_positionwise_scores(sequence, shap_values, k=4)
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start_max, end_max, avg_max = find_extreme_subregion(shap_means, window_size, mode="max")
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start_min, end_min, avg_min = find_extreme_subregion(shap_means, window_size, mode="min")
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results = (
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f"Classification: {classification} "
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f"(probability of human = {pred_human:.3f})\n\n"
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f"Sequence length: {len(sequence):,} bases\n"
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f"Overall GC content: {compute_gc_content(sequence):.1f}%\n\n"
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f"Most human-like {window_size} bp region:\n"
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f"Position {start_max:,} to {end_max:,}\n"
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f"Average SHAP: {avg_max:.4f}\n"
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f"GC content: {compute_gc_content(sequence[start_max:end_max]):.1f}%\n\n"
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f"Least human-like {window_size} bp region:\n"
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f"Position {start_min:,} to {end_min:,}\n"
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f"Average SHAP: {avg_min:.4f}\n"
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f"GC content: {compute_gc_content(sequence[start_min:end_min]):.1f}%"
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)
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kmer_fig = create_importance_bar_plot(shap_values, KMERS_4, top_k=top_k)
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kmer_img = fig_to_image(kmer_fig)
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heatmap_fig = plot_linear_heatmap(shap_means)
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heatmap_img = fig_to_image(heatmap_fig)
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state = {
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"seq": sequence,
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"shap_means": shap_means
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}
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return results, kmer_img, heatmap_img, state, header
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except Exception as e:
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return (f"Error
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###############################################################################
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# 8. SUBREGION ANALYSIS
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###############################################################################
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def analyze_subregion(state, header, region_start, region_end):
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if not state or "seq" not in state or "shap_means" not in state:
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return ("No sequence data found. Please run Step 1 first.", None, None)
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seq = state["seq"]
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shap_means = state["shap_means"]
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region_start = int(region_start)
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region_end = int(region_end)
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if region_end <= region_start:
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return ("Invalid region range. End must be > Start.", None, None)
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region_seq = seq[region_start:region_end]
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region_shap = shap_means[region_start:region_end]
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gc_percent = compute_gc_content(region_seq)
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avg_shap = float(np.mean(region_shap))
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positive_fraction = np.mean(region_shap > 0)
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negative_fraction = np.mean(region_shap < 0)
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if avg_shap > 0.05:
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region_classification = "Likely pushing toward human"
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elif avg_shap < -0.05:
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f"Subregion interpretation: {region_classification}\n"
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)
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heatmap_fig = plot_linear_heatmap(
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shap_means,
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title="Subregion SHAP",
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heatmap_img = fig_to_image(heatmap_fig)
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hist_fig = plot_shap_histogram(region_shap, title="SHAP Distribution in Subregion")
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hist_img = fig_to_image(hist_fig)
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return (region_info, heatmap_img, hist_img)
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###############################################################################
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# 9. COMPARISON ANALYSIS FUNCTIONS
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###############################################################################
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def normalize_shap_lengths(shap1, shap2, num_points=1000):
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x1 = np.linspace(0, 1, len(shap1))
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x2 = np.linspace(0, 1, len(shap2))
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f1 = interp1d(x1, shap1, kind='linear')
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f2 = interp1d(x2, shap2, kind='linear')
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x_new = np.linspace(0, 1, num_points)
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shap1_norm = f1(x_new)
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shap2_norm = f2(x_new)
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return shap1_norm, shap2_norm
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def compute_shap_difference(shap1_norm, shap2_norm):
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return shap2_norm - shap1_norm
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def plot_comparative_heatmap(shap_diff, title="SHAP Difference Heatmap"):
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heatmap_data = shap_diff.reshape(1, -1)
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extent = max(abs(np.min(shap_diff)), abs(np.max(shap_diff)))
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cmap = get_zero_centered_cmap()
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fig, ax = plt.subplots(figsize=(12, 1.8))
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cax = ax.imshow(
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heatmap_data,
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aspect='auto',
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cmap=cmap,
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vmin=-extent,
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vmax=extent
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)
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cbar = plt.colorbar(
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cax,
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orientation='horizontal',
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pad=0.25,
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aspect=40,
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shrink=0.8
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)
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cbar.ax.tick_params(labelsize=8)
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cbar.set_label('SHAP Difference (Seq2 - Seq1)', fontsize=9, labelpad=5)
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ax.set_yticks([])
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ax.set_xlabel('Normalized Position (0-100%)', fontsize=10)
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ax.set_title(title, pad=10)
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plt.subplots_adjust(bottom=0.25, left=0.05, right=0.95)
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return fig
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def analyze_sequence_comparison(file1, file2, fasta1="", fasta2=""):
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results1 = analyze_sequence(file1, top_k=10, fasta_text=fasta1, window_size=500)
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if isinstance(results1[0], str) and "Error" in results1[0]:
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return (f"Error in sequence 1: {results1[0]}", None, None)
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| 452 |
-
|
| 453 |
-
results2 = analyze_sequence(file2, top_k=10, fasta_text=fasta2, window_size=500)
|
| 454 |
-
if isinstance(results2[0], str) and "Error" in results2[0]:
|
| 455 |
-
return (f"Error in sequence 2: {results2[0]}", None, None)
|
| 456 |
-
|
| 457 |
-
shap1 = results1[3]["shap_means"]
|
| 458 |
-
shap2 = results2[3]["shap_means"]
|
| 459 |
-
|
| 460 |
-
shap1_norm, shap2_norm = normalize_shap_lengths(shap1, shap2)
|
| 461 |
-
shap_diff = compute_shap_difference(shap1_norm, shap2_norm)
|
| 462 |
-
|
| 463 |
-
avg_diff = np.mean(shap_diff)
|
| 464 |
-
std_diff = np.std(shap_diff)
|
| 465 |
-
max_diff = np.max(shap_diff)
|
| 466 |
-
min_diff = np.min(shap_diff)
|
| 467 |
-
|
| 468 |
-
threshold = 0.05
|
| 469 |
-
substantial_diffs = np.abs(shap_diff) > threshold
|
| 470 |
-
frac_different = np.mean(substantial_diffs)
|
| 471 |
-
|
| 472 |
-
classification1 = results1[0].split('Classification: ')[1].split('\n')[0].strip()
|
| 473 |
-
classification2 = results2[0].split('Classification: ')[1].split('\n')[0].strip()
|
| 474 |
-
|
| 475 |
-
len1_formatted = "{:,}".format(len(shap1))
|
| 476 |
-
len2_formatted = "{:,}".format(len(shap2))
|
| 477 |
-
frac_formatted = "{:.2%}".format(frac_different)
|
| 478 |
-
|
| 479 |
-
comparison_text = (
|
| 480 |
-
"Sequence Comparison Results:\n"
|
| 481 |
-
f"Sequence 1: {results1[4]}\n"
|
| 482 |
-
f"Length: {len1_formatted} bases\n"
|
| 483 |
-
f"Classification: {classification1}\n\n"
|
| 484 |
-
f"Sequence 2: {results2[4]}\n"
|
| 485 |
-
f"Length: {len2_formatted} bases\n"
|
| 486 |
-
f"Classification: {classification2}\n\n"
|
| 487 |
-
"Comparison Statistics:\n"
|
| 488 |
-
f"Average SHAP difference: {avg_diff:.4f}\n"
|
| 489 |
-
f"Standard deviation: {std_diff:.4f}\n"
|
| 490 |
-
f"Max difference: {max_diff:.4f} (Seq2 more human-like)\n"
|
| 491 |
-
f"Min difference: {min_diff:.4f} (Seq1 more human-like)\n"
|
| 492 |
-
f"Fraction of positions with substantial differences: {frac_formatted}\n\n"
|
| 493 |
-
"Interpretation:\n"
|
| 494 |
-
"Positive values (red) indicate regions where Sequence 2 is more 'human-like'\n"
|
| 495 |
-
"Negative values (blue) indicate regions where Sequence 1 is more 'human-like'"
|
| 496 |
-
)
|
| 497 |
-
|
| 498 |
-
heatmap_fig = plot_comparative_heatmap(shap_diff)
|
| 499 |
-
heatmap_img = fig_to_image(heatmap_fig)
|
| 500 |
-
|
| 501 |
-
hist_fig = plot_shap_histogram(shap_diff, title="Distribution of SHAP Differences")
|
| 502 |
-
hist_img = fig_to_image(hist_fig)
|
| 503 |
-
|
| 504 |
-
return comparison_text, heatmap_img, hist_img
|
| 505 |
|
| 506 |
###############################################################################
|
| 507 |
-
#
|
| 508 |
###############################################################################
|
| 509 |
|
| 510 |
css = """
|
|
@@ -535,14 +507,14 @@ with gr.Blocks(css=css) as iface:
|
|
| 535 |
placeholder=">sequence_name\nACGTACGT...",
|
| 536 |
lines=5
|
| 537 |
)
|
| 538 |
-
|
| 539 |
minimum=5,
|
| 540 |
maximum=30,
|
| 541 |
value=10,
|
| 542 |
step=1,
|
| 543 |
label="Number of top k-mers to display"
|
| 544 |
)
|
| 545 |
-
|
| 546 |
minimum=100,
|
| 547 |
maximum=5000,
|
| 548 |
value=500,
|
|
@@ -561,9 +533,10 @@ with gr.Blocks(css=css) as iface:
|
|
| 561 |
seq_state = gr.State()
|
| 562 |
header_state = gr.State()
|
| 563 |
|
|
|
|
| 564 |
analyze_btn.click(
|
| 565 |
analyze_sequence,
|
| 566 |
-
inputs=[file_input,
|
| 567 |
outputs=[results_box, kmer_img, genome_img, seq_state, header_state]
|
| 568 |
)
|
| 569 |
|
|
@@ -592,61 +565,6 @@ with gr.Blocks(css=css) as iface:
|
|
| 592 |
inputs=[seq_state, header_state, region_start, region_end],
|
| 593 |
outputs=[subregion_info, subregion_img, subregion_hist_img]
|
| 594 |
)
|
| 595 |
-
|
| 596 |
-
with gr.Tab("3) Comparative Analysis"):
|
| 597 |
-
gr.Markdown("""
|
| 598 |
-
**Compare Two Sequences**
|
| 599 |
-
Upload or paste two FASTA sequences to compare their SHAP patterns.
|
| 600 |
-
The sequences will be normalized to the same length for comparison.
|
| 601 |
-
|
| 602 |
-
**Color Scale**:
|
| 603 |
-
- Red: Sequence 2 is more human-like in this region
|
| 604 |
-
- Blue: Sequence 1 is more human-like in this region
|
| 605 |
-
- White: No substantial difference
|
| 606 |
-
""")
|
| 607 |
-
|
| 608 |
-
with gr.Row():
|
| 609 |
-
with gr.Column(scale=1):
|
| 610 |
-
file_input1 = gr.File(
|
| 611 |
-
label="Upload first FASTA file",
|
| 612 |
-
file_types=[".fasta", ".fa", ".txt"],
|
| 613 |
-
type="filepath"
|
| 614 |
-
)
|
| 615 |
-
text_input1 = gr.Textbox(
|
| 616 |
-
label="Or paste first FASTA sequence",
|
| 617 |
-
placeholder=">sequence1\nACGTACGT...",
|
| 618 |
-
lines=5
|
| 619 |
-
)
|
| 620 |
-
|
| 621 |
-
with gr.Column(scale=1):
|
| 622 |
-
file_input2 = gr.File(
|
| 623 |
-
label="Upload second FASTA file",
|
| 624 |
-
file_types=[".fasta", ".fa", ".txt"],
|
| 625 |
-
type="filepath"
|
| 626 |
-
)
|
| 627 |
-
text_input2 = gr.Textbox(
|
| 628 |
-
label="Or paste second FASTA sequence",
|
| 629 |
-
placeholder=">sequence2\nACGTACGT...",
|
| 630 |
-
lines=5
|
| 631 |
-
)
|
| 632 |
-
|
| 633 |
-
compare_btn = gr.Button("Compare Sequences", variant="primary")
|
| 634 |
-
|
| 635 |
-
comparison_text = gr.Textbox(
|
| 636 |
-
label="Comparison Results",
|
| 637 |
-
lines=12,
|
| 638 |
-
interactive=False
|
| 639 |
-
)
|
| 640 |
-
|
| 641 |
-
with gr.Row():
|
| 642 |
-
diff_heatmap = gr.Image(label="SHAP Difference Heatmap")
|
| 643 |
-
diff_hist = gr.Image(label="Distribution of SHAP Differences")
|
| 644 |
-
|
| 645 |
-
compare_btn.click(
|
| 646 |
-
analyze_sequence_comparison,
|
| 647 |
-
inputs=[file_input1, file_input2, text_input1, text_input2],
|
| 648 |
-
outputs=[comparison_text, diff_heatmap, diff_hist]
|
| 649 |
-
)
|
| 650 |
|
| 651 |
gr.Markdown("""
|
| 652 |
### Interface Features
|
|
@@ -660,22 +578,7 @@ with gr.Blocks(css=css) as iface:
|
|
| 660 |
- GC content
|
| 661 |
- Fraction of positions pushing human vs. non-human
|
| 662 |
- Simple logic-based classification
|
| 663 |
-
- **Sequence Comparison**:
|
| 664 |
-
- Compare two sequences to identify regions of difference
|
| 665 |
-
- Normalized comparison to handle different sequence lengths
|
| 666 |
-
- Statistical summary of differences
|
| 667 |
""")
|
| 668 |
|
| 669 |
if __name__ == "__main__":
|
| 670 |
-
|
| 671 |
-
plt.rcParams['figure.figsize'] = [10, 6]
|
| 672 |
-
plt.rcParams['figure.dpi'] = 100
|
| 673 |
-
plt.rcParams['font.size'] = 10
|
| 674 |
-
|
| 675 |
-
iface.launch(
|
| 676 |
-
share=False,
|
| 677 |
-
server_name="0.0.0.0",
|
| 678 |
-
server_port=7860,
|
| 679 |
-
show_api=False,
|
| 680 |
-
debug=False
|
| 681 |
-
)
|
|
|
|
| 1 |
import gradio as gr
|
| 2 |
import torch
|
| 3 |
+
import joblib
|
| 4 |
import numpy as np
|
| 5 |
from itertools import product
|
| 6 |
import torch.nn as nn
|
|
|
|
| 8 |
import matplotlib.colors as mcolors
|
| 9 |
import io
|
| 10 |
from PIL import Image
|
|
|
|
| 11 |
|
| 12 |
###############################################################################
|
| 13 |
# 1. MODEL DEFINITION
|
|
|
|
| 71 |
|
| 72 |
total_kmers = len(sequence) - k + 1
|
| 73 |
if total_kmers > 0:
|
| 74 |
+
vec = vec / total_kmers
|
| 75 |
|
| 76 |
return vec
|
| 77 |
|
|
|
|
| 86 |
"""
|
| 87 |
model.eval()
|
| 88 |
with torch.no_grad():
|
| 89 |
+
# Baseline
|
| 90 |
baseline_output = model(x_tensor)
|
| 91 |
baseline_probs = torch.softmax(baseline_output, dim=1)
|
| 92 |
+
baseline_prob = baseline_probs[0, 1].item() # Probability of 'human' class
|
| 93 |
|
| 94 |
+
# Zeroing each feature to measure impact
|
| 95 |
shap_values = []
|
| 96 |
x_zeroed = x_tensor.clone()
|
| 97 |
for i in range(x_tensor.shape[1]):
|
|
|
|
| 102 |
prob = probs[0, 1].item()
|
| 103 |
impact = baseline_prob - prob
|
| 104 |
shap_values.append(impact)
|
| 105 |
+
x_zeroed[0, i] = original_val # restore
|
| 106 |
return np.array(shap_values), baseline_prob
|
| 107 |
|
| 108 |
###############################################################################
|
|
|
|
| 110 |
###############################################################################
|
| 111 |
|
| 112 |
def compute_positionwise_scores(sequence, shap_values, k=4):
|
| 113 |
+
"""
|
| 114 |
+
Returns an array of per-base SHAP contributions by averaging
|
| 115 |
+
the k-mer SHAP values of all k-mers covering that base.
|
| 116 |
+
"""
|
| 117 |
kmers = [''.join(p) for p in product("ACGT", repeat=k)]
|
| 118 |
kmer_dict = {km: i for i, km in enumerate(kmers)}
|
| 119 |
|
|
|
|
| 138 |
###############################################################################
|
| 139 |
|
| 140 |
def find_extreme_subregion(shap_means, window_size=500, mode="max"):
|
| 141 |
+
"""
|
| 142 |
+
Finds the subregion of length `window_size` that has the maximum
|
| 143 |
+
(mode="max") or minimum (mode="min") average SHAP.
|
| 144 |
+
Returns (best_start, best_end, best_avg).
|
| 145 |
+
"""
|
| 146 |
n = len(shap_means)
|
| 147 |
if n == 0:
|
| 148 |
return (0, 0, 0.0)
|
| 149 |
if window_size >= n:
|
| 150 |
+
# entire sequence
|
| 151 |
avg_val = float(np.mean(shap_means))
|
| 152 |
return (0, n, avg_val)
|
| 153 |
|
| 154 |
+
# We'll build csum of length n+1
|
| 155 |
csum = np.zeros(n + 1, dtype=np.float32)
|
| 156 |
csum[1:] = np.cumsum(shap_means)
|
| 157 |
|
|
|
|
| 178 |
###############################################################################
|
| 179 |
|
| 180 |
def fig_to_image(fig):
|
| 181 |
+
"""Convert a Matplotlib figure to a PIL Image for Gradio."""
|
| 182 |
buf = io.BytesIO()
|
| 183 |
fig.savefig(buf, format='png', bbox_inches='tight', dpi=150)
|
| 184 |
buf.seek(0)
|
|
|
|
| 187 |
return img
|
| 188 |
|
| 189 |
def get_zero_centered_cmap():
|
| 190 |
+
"""
|
| 191 |
+
Creates a custom diverging colormap that is:
|
| 192 |
+
- Blue for negative
|
| 193 |
+
- White for zero
|
| 194 |
+
- Red for positive
|
| 195 |
+
"""
|
| 196 |
colors = [
|
| 197 |
+
(0.0, 'blue'), # negative
|
| 198 |
+
(0.5, 'white'), # zero
|
| 199 |
+
(1.0, 'red') # positive
|
| 200 |
]
|
| 201 |
+
cmap = mcolors.LinearSegmentedColormap.from_list("blue_white_red", colors)
|
| 202 |
+
return cmap
|
| 203 |
|
| 204 |
def plot_linear_heatmap(shap_means, title="Per-base SHAP Heatmap", start=None, end=None):
|
| 205 |
+
"""
|
| 206 |
+
Plots a 1D heatmap of per-base SHAP contributions with a custom colormap:
|
| 207 |
+
- Negative = blue
|
| 208 |
+
- 0 = white
|
| 209 |
+
- Positive = red
|
| 210 |
+
"""
|
| 211 |
if start is not None and end is not None:
|
| 212 |
local_shap = shap_means[start:end]
|
| 213 |
subtitle = f" (positions {start}-{end})"
|
|
|
|
| 218 |
if len(local_shap) == 0:
|
| 219 |
local_shap = np.array([0.0])
|
| 220 |
|
| 221 |
+
# Build 2D array for imshow
|
| 222 |
heatmap_data = local_shap.reshape(1, -1)
|
| 223 |
+
|
| 224 |
+
# Force symmetrical range
|
| 225 |
min_val = np.min(local_shap)
|
| 226 |
max_val = np.max(local_shap)
|
| 227 |
extent = max(abs(min_val), abs(max_val))
|
|
|
|
| 228 |
|
| 229 |
+
# Create custom colormap
|
| 230 |
+
custom_cmap = get_zero_centered_cmap()
|
| 231 |
+
|
| 232 |
+
# Create figure with adjusted height ratio
|
| 233 |
+
fig, ax = plt.subplots(figsize=(12, 1.8)) # Reduced height
|
| 234 |
+
|
| 235 |
+
# Plot heatmap
|
| 236 |
cax = ax.imshow(
|
| 237 |
heatmap_data,
|
| 238 |
aspect='auto',
|
| 239 |
+
cmap=custom_cmap,
|
| 240 |
vmin=-extent,
|
| 241 |
+
vmax=+extent
|
| 242 |
)
|
| 243 |
+
|
| 244 |
+
# Configure colorbar with more subtle positioning
|
| 245 |
cbar = plt.colorbar(
|
| 246 |
cax,
|
| 247 |
orientation='horizontal',
|
| 248 |
+
pad=0.25, # Reduced padding
|
| 249 |
+
aspect=40, # Make colorbar thinner
|
| 250 |
+
shrink=0.8 # Make colorbar shorter than plot width
|
| 251 |
)
|
|
|
|
|
|
|
| 252 |
|
| 253 |
+
# Style the colorbar
|
| 254 |
+
cbar.ax.tick_params(labelsize=8) # Smaller tick labels
|
| 255 |
+
cbar.set_label(
|
| 256 |
+
'SHAP Contribution',
|
| 257 |
+
fontsize=9,
|
| 258 |
+
labelpad=5
|
| 259 |
+
)
|
| 260 |
+
|
| 261 |
+
# Configure main plot
|
| 262 |
ax.set_yticks([])
|
| 263 |
ax.set_xlabel('Position in Sequence', fontsize=10)
|
| 264 |
ax.set_title(f"{title}{subtitle}", pad=10)
|
| 265 |
+
|
| 266 |
+
# Fine-tune layout
|
| 267 |
+
plt.subplots_adjust(
|
| 268 |
+
bottom=0.25, # Reduced bottom margin
|
| 269 |
+
left=0.05, # Tighter left margin
|
| 270 |
+
right=0.95 # Tighter right margin
|
| 271 |
+
)
|
| 272 |
|
| 273 |
return fig
|
| 274 |
|
| 275 |
def create_importance_bar_plot(shap_values, kmers, top_k=10):
|
| 276 |
+
"""Create a bar plot of the most important k-mers."""
|
| 277 |
plt.rcParams.update({'font.size': 10})
|
| 278 |
fig = plt.figure(figsize=(10, 5))
|
| 279 |
|
| 280 |
+
# Sort by absolute importance
|
| 281 |
indices = np.argsort(np.abs(shap_values))[-top_k:]
|
| 282 |
values = shap_values[indices]
|
| 283 |
features = [kmers[i] for i in indices]
|
| 284 |
|
| 285 |
+
# negative -> blue, positive -> red
|
| 286 |
colors = ['#99ccff' if v < 0 else '#ff9999' for v in values]
|
| 287 |
+
|
| 288 |
plt.barh(range(len(values)), values, color=colors)
|
| 289 |
plt.yticks(range(len(values)), features)
|
| 290 |
plt.xlabel('SHAP Value (impact on model output)')
|
|
|
|
| 294 |
return fig
|
| 295 |
|
| 296 |
def plot_shap_histogram(shap_array, title="SHAP Distribution in Region"):
|
| 297 |
+
"""
|
| 298 |
+
Simple histogram of SHAP values in the subregion.
|
| 299 |
+
"""
|
| 300 |
fig, ax = plt.subplots(figsize=(6, 4))
|
| 301 |
ax.hist(shap_array, bins=30, color='gray', edgecolor='black')
|
| 302 |
ax.axvline(0, color='red', linestyle='--', label='0.0')
|
|
|
|
| 308 |
return fig
|
| 309 |
|
| 310 |
def compute_gc_content(sequence):
|
| 311 |
+
"""Compute %GC in the sequence (A, C, G, T)."""
|
| 312 |
if not sequence:
|
| 313 |
return 0
|
| 314 |
gc_count = sequence.count('G') + sequence.count('C')
|
| 315 |
return (gc_count / len(sequence)) * 100.0
|
| 316 |
|
| 317 |
###############################################################################
|
| 318 |
+
# 7. MAIN ANALYSIS STEP (Gradio Step 1)
|
| 319 |
###############################################################################
|
| 320 |
|
| 321 |
+
def analyze_sequence(file_obj, top_kmers=10, fasta_text="", window_size=500):
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
| 322 |
"""
|
| 323 |
+
Analyzes the entire genome, returning classification, full-genome heatmap,
|
| 324 |
+
top k-mer bar plot, and identifies subregions with strongest positive/negative push.
|
| 325 |
"""
|
| 326 |
+
# Handle input
|
| 327 |
+
if fasta_text.strip():
|
| 328 |
+
text = fasta_text.strip()
|
| 329 |
+
elif file_obj is not None:
|
| 330 |
+
try:
|
| 331 |
+
with open(file_obj, 'r') as f:
|
| 332 |
+
text = f.read()
|
| 333 |
+
except Exception as e:
|
| 334 |
+
return (f"Error reading file: {str(e)}", None, None, None, None)
|
| 335 |
+
else:
|
| 336 |
+
return ("Please provide a FASTA sequence.", None, None, None, None)
|
| 337 |
+
|
| 338 |
+
# Parse FASTA
|
| 339 |
+
sequences = parse_fasta(text)
|
| 340 |
+
if not sequences:
|
| 341 |
+
return ("No valid FASTA sequences found.", None, None, None, None)
|
| 342 |
+
|
| 343 |
+
header, seq = sequences[0]
|
| 344 |
+
|
| 345 |
+
# Load model and scaler
|
| 346 |
+
device = torch.device('cuda' if torch.cuda.is_available() else 'cpu')
|
| 347 |
try:
|
| 348 |
+
# Use weights_only=True for safer loading
|
| 349 |
+
state_dict = torch.load('model.pt', map_location=device, weights_only=True)
|
| 350 |
+
model = VirusClassifier(256).to(device)
|
| 351 |
+
model.load_state_dict(state_dict)
|
|
|
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|
| 352 |
|
| 353 |
+
scaler = joblib.load('scaler.pkl')
|
| 354 |
except Exception as e:
|
| 355 |
+
return (f"Error loading model/scaler: {str(e)}", None, None, None, None)
|
| 356 |
+
|
| 357 |
+
# Vectorize + scale
|
| 358 |
+
freq_vector = sequence_to_kmer_vector(seq)
|
| 359 |
+
scaled_vector = scaler.transform(freq_vector.reshape(1, -1))
|
| 360 |
+
x_tensor = torch.FloatTensor(scaled_vector).to(device)
|
| 361 |
+
|
| 362 |
+
# SHAP + classification
|
| 363 |
+
shap_values, prob_human = calculate_shap_values(model, x_tensor)
|
| 364 |
+
prob_nonhuman = 1.0 - prob_human
|
| 365 |
+
|
| 366 |
+
classification = "Human" if prob_human > 0.5 else "Non-human"
|
| 367 |
+
confidence = max(prob_human, prob_nonhuman)
|
| 368 |
+
|
| 369 |
+
# Per-base SHAP
|
| 370 |
+
shap_means = compute_positionwise_scores(seq, shap_values, k=4)
|
| 371 |
+
|
| 372 |
+
# Find the most "human-pushing" region
|
| 373 |
+
(max_start, max_end, max_avg) = find_extreme_subregion(shap_means, window_size, mode="max")
|
| 374 |
+
# Find the most "non-human–pushing" region
|
| 375 |
+
(min_start, min_end, min_avg) = find_extreme_subregion(shap_means, window_size, mode="min")
|
| 376 |
+
|
| 377 |
+
# Build results text
|
| 378 |
+
results_text = (
|
| 379 |
+
f"Sequence: {header}\n"
|
| 380 |
+
f"Length: {len(seq):,} bases\n"
|
| 381 |
+
f"Classification: {classification}\n"
|
| 382 |
+
f"Confidence: {confidence:.3f}\n"
|
| 383 |
+
f"(Human Probability: {prob_human:.3f}, Non-human Probability: {prob_nonhuman:.3f})\n\n"
|
| 384 |
+
f"---\n"
|
| 385 |
+
f"**Most Human-Pushing {window_size}-bp Subregion**:\n"
|
| 386 |
+
f"Start: {max_start}, End: {max_end}, Avg SHAP: {max_avg:.4f}\n\n"
|
| 387 |
+
f"**Most Non-Human–Pushing {window_size}-bp Subregion**:\n"
|
| 388 |
+
f"Start: {min_start}, End: {min_end}, Avg SHAP: {min_avg:.4f}"
|
| 389 |
+
)
|
| 390 |
+
|
| 391 |
+
# K-mer importance plot
|
| 392 |
+
kmers = [''.join(p) for p in product("ACGT", repeat=4)]
|
| 393 |
+
bar_fig = create_importance_bar_plot(shap_values, kmers, top_kmers)
|
| 394 |
+
bar_img = fig_to_image(bar_fig)
|
| 395 |
+
|
| 396 |
+
# Full-genome SHAP heatmap
|
| 397 |
+
heatmap_fig = plot_linear_heatmap(shap_means, title="Genome-wide SHAP")
|
| 398 |
+
heatmap_img = fig_to_image(heatmap_fig)
|
| 399 |
+
|
| 400 |
+
# Store data for subregion analysis
|
| 401 |
+
state_dict_out = {
|
| 402 |
+
"seq": seq,
|
| 403 |
+
"shap_means": shap_means
|
| 404 |
+
}
|
| 405 |
+
|
| 406 |
+
return (results_text, bar_img, heatmap_img, state_dict_out, header)
|
| 407 |
|
| 408 |
###############################################################################
|
| 409 |
+
# 8. SUBREGION ANALYSIS (Gradio Step 2)
|
| 410 |
###############################################################################
|
| 411 |
|
| 412 |
def analyze_subregion(state, header, region_start, region_end):
|
| 413 |
+
"""
|
| 414 |
+
Takes stored data from step 1 and a user-chosen region.
|
| 415 |
+
Returns a subregion heatmap, histogram, and some stats (GC, average SHAP).
|
| 416 |
+
"""
|
| 417 |
if not state or "seq" not in state or "shap_means" not in state:
|
| 418 |
return ("No sequence data found. Please run Step 1 first.", None, None)
|
| 419 |
|
| 420 |
seq = state["seq"]
|
| 421 |
shap_means = state["shap_means"]
|
| 422 |
|
| 423 |
+
# Validate bounds
|
| 424 |
region_start = int(region_start)
|
| 425 |
region_end = int(region_end)
|
| 426 |
|
|
|
|
| 429 |
if region_end <= region_start:
|
| 430 |
return ("Invalid region range. End must be > Start.", None, None)
|
| 431 |
|
| 432 |
+
# Subsequence
|
| 433 |
region_seq = seq[region_start:region_end]
|
| 434 |
region_shap = shap_means[region_start:region_end]
|
| 435 |
|
| 436 |
+
# Some stats
|
| 437 |
gc_percent = compute_gc_content(region_seq)
|
| 438 |
avg_shap = float(np.mean(region_shap))
|
| 439 |
|
| 440 |
+
# Fraction pushing toward human vs. non-human
|
| 441 |
positive_fraction = np.mean(region_shap > 0)
|
| 442 |
negative_fraction = np.mean(region_shap < 0)
|
| 443 |
|
| 444 |
+
# Simple logic-based interpretation
|
| 445 |
if avg_shap > 0.05:
|
| 446 |
region_classification = "Likely pushing toward human"
|
| 447 |
elif avg_shap < -0.05:
|
|
|
|
| 459 |
f"Subregion interpretation: {region_classification}\n"
|
| 460 |
)
|
| 461 |
|
| 462 |
+
# Plot region as small heatmap
|
| 463 |
heatmap_fig = plot_linear_heatmap(
|
| 464 |
shap_means,
|
| 465 |
title="Subregion SHAP",
|
|
|
|
| 468 |
)
|
| 469 |
heatmap_img = fig_to_image(heatmap_fig)
|
| 470 |
|
| 471 |
+
# Plot histogram of SHAP in region
|
| 472 |
hist_fig = plot_shap_histogram(region_shap, title="SHAP Distribution in Subregion")
|
| 473 |
hist_img = fig_to_image(hist_fig)
|
| 474 |
|
| 475 |
return (region_info, heatmap_img, hist_img)
|
| 476 |
|
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|
| 477 |
|
| 478 |
###############################################################################
|
| 479 |
+
# 9. BUILD GRADIO INTERFACE
|
| 480 |
###############################################################################
|
| 481 |
|
| 482 |
css = """
|
|
|
|
| 507 |
placeholder=">sequence_name\nACGTACGT...",
|
| 508 |
lines=5
|
| 509 |
)
|
| 510 |
+
top_k = gr.Slider(
|
| 511 |
minimum=5,
|
| 512 |
maximum=30,
|
| 513 |
value=10,
|
| 514 |
step=1,
|
| 515 |
label="Number of top k-mers to display"
|
| 516 |
)
|
| 517 |
+
win_size = gr.Slider(
|
| 518 |
minimum=100,
|
| 519 |
maximum=5000,
|
| 520 |
value=500,
|
|
|
|
| 533 |
seq_state = gr.State()
|
| 534 |
header_state = gr.State()
|
| 535 |
|
| 536 |
+
# analyze_sequence(...) returns 5 items
|
| 537 |
analyze_btn.click(
|
| 538 |
analyze_sequence,
|
| 539 |
+
inputs=[file_input, top_k, text_input, win_size],
|
| 540 |
outputs=[results_box, kmer_img, genome_img, seq_state, header_state]
|
| 541 |
)
|
| 542 |
|
|
|
|
| 565 |
inputs=[seq_state, header_state, region_start, region_end],
|
| 566 |
outputs=[subregion_info, subregion_img, subregion_hist_img]
|
| 567 |
)
|
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|
| 568 |
|
| 569 |
gr.Markdown("""
|
| 570 |
### Interface Features
|
|
|
|
| 578 |
- GC content
|
| 579 |
- Fraction of positions pushing human vs. non-human
|
| 580 |
- Simple logic-based classification
|
|
|
|
|
|
|
|
|
|
|
|
|
| 581 |
""")
|
| 582 |
|
| 583 |
if __name__ == "__main__":
|
| 584 |
+
iface.launch()
|
|
|
|
|
|
|
|
|
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|
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