File size: 7,710 Bytes
ccd282b
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125
126
127
128
129
130
131
132
133
134
135
136
137
138
139
140
141
142
143
144
145
146
147
148
149
150
151
152
153
154
155
156
157
158
159
160
161
162
163
164
165
166
167
168
169
170
171
172
173
174
175
176
177
178
179
180
181
182
183
184
185
186
187
188
189
190
191
192
193
194
195
196
197
198
199
200
201
202
203
204
205
206
207
208
209
210
211
212
213
#!/usr/bin/env python
"""
NB-Transformer Example Usage Script

This script demonstrates the basic usage of NB-Transformer for fast
Negative Binomial GLM parameter estimation. 

Run this script to see NB-Transformer in action:
    python example_usage.py
"""

import numpy as np
from nb_transformer import load_pretrained_model, quick_inference_example

def basic_example():
    """Basic parameter estimation example."""
    print("🚀 NB-TRANSFORMER BASIC EXAMPLE")
    print("=" * 50)
    
    # Load the pre-trained model
    print("Loading pre-trained NB-Transformer model...")
    model = load_pretrained_model()
    print("✅ Model loaded successfully!")
    
    # Example data (log10(CPM + 1) transformed)
    control_samples = [2.1, 1.8, 2.3, 2.0, 1.9]        # 5 control samples
    treatment_samples = [1.5, 1.2, 1.7, 1.4, 1.6]      # 5 treatment samples
    
    print(f"\n📊 INPUT DATA")
    print(f"Control samples (n={len(control_samples)}): {control_samples}")
    print(f"Treatment samples (n={len(treatment_samples)}): {treatment_samples}")
    
    # Predict NB GLM parameters
    print(f"\n⚡ RUNNING INFERENCE...")
    params = model.predict_parameters(control_samples, treatment_samples)
    
    # Display results
    print(f"\n📈 RESULTS")
    print(f"μ̂ (base mean, log scale): {params['mu']:.3f}")
    print(f"β̂ (log fold change): {params['beta']:.3f}")
    print(f"α̂ (log dispersion): {params['alpha']:.3f}")
    
    # Interpret results
    fold_change = np.exp(params['beta'])
    if fold_change > 1:
        direction = "upregulated"
        magnitude = f"{fold_change:.2f}x"
    else:
        direction = "downregulated" 
        magnitude = f"{1/fold_change:.2f}x"
    
    print(f"\n🧬 BIOLOGICAL INTERPRETATION")
    print(f"Fold change: {fold_change:.2f}x")
    print(f"Gene appears to be {direction} ({magnitude})")
    print(f"Base expression level: {np.exp(params['mu']):.2f}")
    print(f"Dispersion parameter: {np.exp(params['alpha']):.3f}")
    
    return params


def statistical_inference_example():
    """Complete statistical inference example with p-values."""
    print(f"\n\n🔬 COMPLETE STATISTICAL INFERENCE EXAMPLE")
    print("=" * 50)
    
    from nb_transformer.inference import compute_nb_glm_inference
    
    # Load model
    model = load_pretrained_model()
    
    # Simulate realistic RNA-seq data
    print("📊 SIMULATING REALISTIC RNA-SEQ DATA")
    
    # Control condition
    control_counts = np.array([1520, 1280, 1650, 1400, 1350])
    control_lib_sizes = np.array([1e6, 1.1e6, 0.9e6, 1.05e6, 0.95e6])
    
    # Treatment condition (downregulated gene)
    treatment_counts = np.array([980, 890, 1100, 950, 850])
    treatment_lib_sizes = np.array([1e6, 1.0e6, 1.1e6, 0.95e6, 1.02e6])
    
    print(f"Control counts: {control_counts}")
    print(f"Treatment counts: {treatment_counts}")
    print(f"Control library sizes: {np.mean(control_lib_sizes)/1e6:.2f}M (avg)")
    print(f"Treatment library sizes: {np.mean(treatment_lib_sizes)/1e6:.2f}M (avg)")
    
    # Transform to log10(CPM + 1) 
    control_transformed = np.log10(1e4 * control_counts / control_lib_sizes + 1)
    treatment_transformed = np.log10(1e4 * treatment_counts / treatment_lib_sizes + 1)
    
    print(f"\n⚡ PARAMETER ESTIMATION")
    params = model.predict_parameters(control_transformed, treatment_transformed)
    
    print(f"\n🧮 STATISTICAL INFERENCE")  
    # Complete statistical analysis with p-values
    results = compute_nb_glm_inference(
        params['mu'], params['beta'], params['alpha'],
        control_counts, treatment_counts,
        control_lib_sizes, treatment_lib_sizes
    )
    
    print(f"Parameter estimates:")
    print(f"  μ̂ = {results['mu']:.3f} (base mean)")
    print(f"  β̂ = {results['beta']:.3f} ± {results['se_beta']:.3f} (log fold change)")
    print(f"  α̂ = {results['alpha']:.3f} (log dispersion)")
    
    print(f"\nStatistical test results:")
    print(f"  Wald statistic: {results['wald_stat']:.3f}")
    print(f"  P-value: {results['pvalue']:.2e}")
    print(f"  Significant (α=0.05): {'✅ Yes' if results['pvalue'] < 0.05 else '❌ No'}")
    
    # Confidence interval
    z_alpha = 1.96  # 95% CI
    ci_lower = results['beta'] - z_alpha * results['se_beta']
    ci_upper = results['beta'] + z_alpha * results['se_beta']
    
    print(f"\n📊 95% CONFIDENCE INTERVAL")
    print(f"Log fold change: [{ci_lower:.3f}, {ci_upper:.3f}]")
    print(f"Fold change: [{np.exp(ci_lower):.3f}x, {np.exp(ci_upper):.3f}x]")
    
    return results


def speed_comparison_example():
    """Demonstrate speed advantage over classical methods."""
    print(f"\n\n⚡ SPEED COMPARISON EXAMPLE") 
    print("=" * 50)
    
    import time
    
    # Load model
    model = load_pretrained_model()
    
    # Generate test data
    n_tests = 100
    print(f"Running {n_tests} parameter estimation tests...")
    
    test_cases = []
    for _ in range(n_tests):
        control = np.random.lognormal(0, 0.5, 5)
        treatment = np.random.lognormal(0, 0.5, 5) 
        test_cases.append((control, treatment))
    
    # Time NB-Transformer
    print(f"\n🚀 Testing NB-Transformer speed...")
    start_time = time.perf_counter()
    
    for control, treatment in test_cases:
        params = model.predict_parameters(control, treatment)
    
    transformer_time = time.perf_counter() - start_time
    transformer_avg = (transformer_time / n_tests) * 1000  # ms per test
    
    print(f"NB-Transformer: {transformer_time:.3f}s total, {transformer_avg:.3f}ms per test")
    
    # Compare with Method of Moments (fastest baseline)
    print(f"\n📊 Testing Method of Moments speed...")
    from nb_transformer import estimate_batch_parameters_vectorized
    
    start_time = time.perf_counter()
    
    control_batch = [case[0] for case in test_cases]
    treatment_batch = [case[1] for case in test_cases]
    results = estimate_batch_parameters_vectorized(control_batch, treatment_batch)
    
    mom_time = time.perf_counter() - start_time
    mom_avg = (mom_time / n_tests) * 1000  # ms per test
    
    print(f"Method of Moments: {mom_time:.3f}s total, {mom_avg:.3f}ms per test")
    
    # Speed comparison
    if mom_avg > 0:
        speedup = mom_avg / transformer_avg
        print(f"\n🏃 SPEED COMPARISON")
        print(f"NB-Transformer vs Method of Moments: {speedup:.1f}x {'faster' if speedup > 1 else 'slower'}")
    
    print(f"\n💡 Note: Classical GLM is typically ~15x slower than NB-Transformer")
    print(f"Expected classical GLM time: ~{transformer_avg * 15:.1f}ms per test")


def main():
    """Run all examples."""
    print("🧬 NB-TRANSFORMER DEMONSTRATION")
    print("=" * 60)
    print("Fast Negative Binomial GLM Parameter Estimation")
    print("A modern replacement for DESeq2 statistical analysis")
    print("=" * 60)
    
    try:
        # Run examples
        basic_example()
        statistical_inference_example()  
        speed_comparison_example()
        
        print(f"\n\n✨ QUICK INFERENCE EXAMPLE")
        print("=" * 50)
        quick_inference_example()
        
        print(f"\n\n🎉 ALL EXAMPLES COMPLETED SUCCESSFULLY!")
        print("=" * 50)
        print("🚀 Ready to use NB-Transformer in your research!")
        print("📚 See examples/ directory for validation scripts")
        print("🔗 Visit https://huggingface.co/valsv/nb-transformer for more info")
        
    except Exception as e:
        print(f"\n❌ Error running examples: {e}")
        print("Please ensure nb-transformer is properly installed:")
        print("   pip install nb-transformer")
        raise


if __name__ == '__main__':
    main()