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"sdm_cost_max": 118638.0 + "sdm_cost_max": 118638.0, + "fold_sampling": 6.0, + "skew": 1.5 } ] \ No newline at end of file diff --git a/docs/cost_data/default_costs.json b/docs/cost_data/default_costs.json index 7ca4d24..87d86a4 100644 --- a/docs/cost_data/default_costs.json +++ b/docs/cost_data/default_costs.json @@ -2,11 +2,11 @@ "usortm": { "synthesis": 1374.02, "cloning": 53.6, - "sorting": 202.5, - "barcoding": 488.65, + "sorting": 283.5, + "barcoding": 1075.03, "sequencing": 500, "hitpicking": 79.68, - "total": 2698.45 + "total": 3365.83 }, "traditional": { "synthesis": 10500.0, @@ -23,19 +23,20 @@ "sequencing": 500, "total": 10969.0 }, - "savings": 6.36, - "per_variant_usortm": 5.4, + "savings": 5.1, + "per_variant_usortm": 6.73, "per_variant_traditional": 34.35, "per_variant_sdm": 21.94, - "wells": 2000, - "plates": 6, + "wells": 4250.0, + "plates": 12.0, + "fold_sampling": 8.5, "timeline": { "assembly_days": 2, "sort_days": 1, - "barcode_days": 1, + "barcode_days": 2, "seq_days": 3, "demux_days": 1, - "total_days": 8, + "total_days": 9, "timeline": [ { "step": "Library Assembly", @@ -52,19 +53,19 @@ { "step": "PCR Barcoding", "start": 3, - "end": 4, - "days": 1 + "end": 5, + "days": 2 }, { "step": "Sequencing", - "start": 4, - "end": 7, + "start": 5, + "end": 8, "days": 3 }, { "step": "Demux & Analysis", - "start": 7, - "end": 8, + "start": 8, + "end": 9, "days": 1 } ] diff --git a/docs/generate_cost_data.py b/docs/generate_cost_data.py index 74890f6..507c50f 100644 --- a/docs/generate_cost_data.py +++ b/docs/generate_cost_data.py @@ -28,17 +28,55 @@ sdm_transformation_cost, sdm_consumables_cost, ) +from usortm.costs.method_loader import load_all_methods, compute_cost +from usortm.simulate.sortm import find_fold_sampling from usortm.costs.time_functions import calculate_total_timeline +_methods_cache = None -def calculate_usortm_cost(lib_size, seq_length): - """Calculate total uSort-M cost with 4x fold sampling.""" - foldSampling = 4 - wells = lib_size * foldSampling +def _get_methods(): + global _methods_cache + if _methods_cache is None: + _methods_cache = load_all_methods() + return _methods_cache - cost = usortm_synthesis_cost(lib_size, seq_length) + +def _gene_pools_synthesis_cost(lib_size, seq_length): + """Twist Gene Pools synthesis cost for sequences > 350 bp.""" + m = _get_methods().get("twist_gene_pools") + if m is None: + return 0 + cost = compute_cost(m, lib_size, seq_length) + return cost if cost is not None else 0 + + +def _compute_fold_sampling(skew, ref_lib_size=500): + """Simulate fold-sampling required for 90% coverage at a given skew.""" + fold, _ = find_fold_sampling( + target_coverage=0.90, + lib_size=ref_lib_size, + skew=skew, + n_sims=100, + seed=42, + ) + return fold + + +def calculate_usortm_cost(lib_size, seq_length, fold_sampling): + """Calculate total uSort-M cost using the given fold-sampling. + + Uses Twist Oligo Pools synthesis for <=350 bp and Twist Gene Pools for longer sequences. + """ + wells = lib_size * fold_sampling + + if seq_length <= 350: + synthesis = usortm_synthesis_cost(lib_size, seq_length) + else: + synthesis = _gene_pools_synthesis_cost(lib_size, seq_length) + + cost = synthesis cost += usortm_cloning_cost(lib_size) - cost += usortm_sorting_cost(lib_size, fold_sampling=foldSampling) + cost += usortm_sorting_cost(lib_size, fold_sampling=fold_sampling) cost += usortm_barcoding_cost(n_wells=wells) cost += usortm_sequencing_cost(n_wells=wells, seq_length=seq_length) cost += usortm_hitpicking_cost(lib_size, seq_length) @@ -71,12 +109,12 @@ def calculate_traditional_range(lib_size, seq_length): return min_cost + common, max_cost + common -def generate_cost_curves(seq_length, max_lib_size=5000, step=25): +def generate_cost_curves(seq_length, fold_sampling, skew, max_lib_size=5000, step=25): """Generate cost curves for plotting.""" data = [] for lib_size in range(50, max_lib_size + 1, step): - usortm_cost = calculate_usortm_cost(lib_size, seq_length) + usortm_cost = calculate_usortm_cost(lib_size, seq_length, fold_sampling) trad_cost = calculate_traditional_cost(lib_size, seq_length) trad_min, trad_max = calculate_traditional_range(lib_size, seq_length) @@ -91,23 +129,28 @@ def generate_cost_curves(seq_length, max_lib_size=5000, step=25): 'traditional_max': round(trad_max, 2), 'sdm_cost': round(sdm_cost, 2), 'sdm_cost_max': round(sdm_cost_max, 2), + 'fold_sampling': round(fold_sampling, 1), + 'skew': skew, }) return data -def generate_detailed_costs(lib_size, seq_length): +def generate_detailed_costs(lib_size, seq_length, fold_sampling): """Generate detailed breakdown of costs for a specific configuration.""" - # Calculate derived values first (needed for cost functions) - foldSampling = 4 - wells = lib_size * foldSampling + wells = lib_size * fold_sampling plates = max(1, -(-wells // 384)) # Ceiling division # uSort-M breakdown + if seq_length <= 350: + synthesis_cost = usortm_synthesis_cost(lib_size, seq_length) + else: + synthesis_cost = _gene_pools_synthesis_cost(lib_size, seq_length) + usortm_breakdown = { - 'synthesis': usortm_synthesis_cost(lib_size, seq_length), + 'synthesis': synthesis_cost, 'cloning': usortm_cloning_cost(lib_size), - 'sorting': usortm_sorting_cost(lib_size, fold_sampling=foldSampling), + 'sorting': usortm_sorting_cost(lib_size, fold_sampling=fold_sampling), 'barcoding': usortm_barcoding_cost(n_wells=wells), 'sequencing': usortm_sequencing_cost(n_wells=wells, seq_length=seq_length), 'hitpicking': usortm_hitpicking_cost(lib_size, seq_length), @@ -124,7 +167,7 @@ def generate_detailed_costs(lib_size, seq_length): trad_breakdown['total'] = sum(trad_breakdown.values()) # Calculate timeline - timeline = calculate_total_timeline(lib_size, seq_length, fold_sampling=foldSampling) + timeline = calculate_total_timeline(lib_size, seq_length, fold_sampling=fold_sampling) # SDM breakdown sdm_breakdown = { @@ -146,6 +189,7 @@ def generate_detailed_costs(lib_size, seq_length): 'per_variant_sdm': round(sdm_breakdown['total'] / lib_size, 2), 'wells': wells, 'plates': plates, + 'fold_sampling': round(fold_sampling, 1), 'timeline': timeline, } @@ -155,11 +199,30 @@ def main(): output_dir = os.path.join(os.path.dirname(__file__), 'cost_data') os.makedirs(output_dir, exist_ok=True) + methods = _get_methods() + + # Simulate fold-sampling required for 90% coverage for each synthesis method. + # Twist Oligo Pools (<=350 bp) and Twist Gene Pools (>350 bp) have different skews. + m_short = methods.get("twist_oligo_pools") + m_long = methods.get("twist_gene_pools") + skew_short = m_short.skew_q90_q10 if m_short else 4.0 + skew_long = m_long.skew_q90_q10 if m_long else 1.5 + + print(f"Simulating fold-sampling for short libraries (skew={skew_short:.1f}×, Twist Oligo Pools)...") + fold_short = _compute_fold_sampling(skew_short) + print(f" → {fold_short:.1f}× fold-sampling for 90% coverage") + + print(f"Simulating fold-sampling for long libraries (skew={skew_long:.1f}×, Twist Gene Pools)...") + fold_long = _compute_fold_sampling(skew_long) + print(f" → {fold_long:.1f}× fold-sampling for 90% coverage") + # Generate curves for all sequence lengths from 100-1500 bp in 50 bp steps seq_lengths = list(range(100, 1501, 50)) for seq_len in seq_lengths: - curve_data = generate_cost_curves(seq_len) + fold = fold_short if seq_len <= 350 else fold_long + skew = skew_short if seq_len <= 350 else skew_long + curve_data = generate_cost_curves(seq_len, fold, skew) filename = f'cost_curve_{seq_len}bp.json' with open(os.path.join(output_dir, filename), 'w') as f: @@ -167,8 +230,8 @@ def main(): print(f"✓ Generated {filename}") - # Generate detailed costs for default configuration - default_config = generate_detailed_costs(500, 300) + # Generate detailed costs for default configuration (300 bp, short library) + default_config = generate_detailed_costs(500, 300, fold_short) with open(os.path.join(output_dir, 'default_costs.json'), 'w') as f: json.dump(default_config, f, indent=2) diff --git a/docs/index.html b/docs/index.html index c3305b9..65a7a37 100644 --- a/docs/index.html +++ b/docs/index.html @@ -858,7 +858,11 @@