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paper-releases/pbisc-diffusion/updates/20261008T125804Z-deck-fig2-3-healthy-fig5-rare/diffusion/dataset/server_1/model8/presentations/2026-09-30--paper-summary--r00/figures/fig2_healthy_cells.pdf ADDED
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paper-releases/pbisc-diffusion/updates/20261008T125804Z-deck-fig2-3-healthy-fig5-rare/diffusion/dataset/server_1/model8/presentations/2026-09-30--paper-summary--r00/tools/fig5_rare_states.py ADDED
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+ #!/usr/bin/env python3
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+ """Fig. 5 rare-cell slides of the 2026-09-30 paper-summary deck (2026-10-08; user decision of that day: Fig. 5 shows the
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+ fraction of rare cells and how well rare states are found, on the paired disease cohorts; main comparison = 5 pairs,
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+ LoRA-5 vs scSemiProfiler-5; 5-fold reported separately).
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+
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+ CPU only, plotting only. Source: plans/rare_states_paired_20261008/out/{summary,contrasts}.csv (tools/rare_paired.py:
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+ benchmark labels and Poisson read-out reproduced cell by cell; literature marker rules of
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+ plans/rare_states_screen_20261004/tools/states.json; observed parent cells thinned to the generated parent depth).
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+ State x cohort pairs are shown when the observed cells hold enough of the state to judge it: >= MIN_OBS state cells
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+ (native depth, scored donors) in >= MIN_DONORS donors; the negative control is left out.
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+ fraction generated % / observed % (thinned) of the state within its parent, log2 (0 = exact; band = within 2-fold)
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+ donors Spearman over donors of generated % vs observed %
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+ direction case-vs-control difference of donor means has the observed sign (5 donors: share of draws)
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+ Slides:
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+ A "Rare states with 5 pairs: how many cells" fraction, LoRA-5 vs scSemiProfiler-5 vs zero-shot
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+ B "Rare states with 5 pairs: in the right donors" donor Spearman and disease direction
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+ C "5-fold CV: rare states" both, reported separately
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+ Outputs: figures/fig5_rare_{fraction,donors,fivefold}.{png,pdf}, data/fig5_rare_states.csv,
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+ data/fig5_rare_states_slide_text.json
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+ """
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+ from __future__ import annotations
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+
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+ import json
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+ import os
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+ import sys
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+ from pathlib import Path
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+
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+ os.environ["CUDA_VISIBLE_DEVICES"] = "" # plotting only
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+
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+ import numpy as np
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+ import pandas as pd
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+
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+ DECK = Path(__file__).resolve().parents[1]
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+ sys.path.insert(0, str(DECK / "tools"))
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+ import style as ST # noqa: E402
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+ import matplotlib.pyplot as plt # noqa: E402
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+ from matplotlib.lines import Line2D # noqa: E402
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+
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+ SRC = Path("/home/sj_server_1/PBISC/immun-pbmc-fm/model_8_sparse_data_diffusion/plans/rare_states_paired_20261008/out")
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+ FIG, DAT = DECK / "figures", DECK / "data"
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+ NAME = {"ye2026_sepsis": "Sepsis", "imperial_eskd": "Imperial", "giroux2022": "Giroux", "ji2025_chili": "Ji"}
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+ MIN_OBS, MIN_DONORS = 30, 3
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+ NEG = "negative control"
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+ FEW = [("zs_raw", "Zero-shot, real bulk", ST.ARM["zs_raw"], "o"), ("scsemi5", "scSemiProfiler, 5 donors", ST.ARM["scsemi"], "D"),
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+ ("lora5", "PBISC LoRA, 5 donors", ST.ARM["lora"], "o")]
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+ POOL = [("zs__raw", "Zero-shot, real bulk", ST.ARM["zs_raw"], "o"), ("scsemi__raw", "scSemiProfiler, same pairs", ST.ARM["scsemi"], "D"),
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+ ("real_lora__raw", "PBISC LoRA", ST.ARM["lora"], "o")]
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+ SHORT = {"C1Q-high monocyte (reference)": "C1Q-high mono", "Cycling T/NK": "Cycling T/NK",
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+ "Cycling activated T (CD38/HLA-DR)": "Cycling act. T", "Proliferating T (label)": "Prolif. T (label)",
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+ "Plasmablast (label)": "Plasmablast (label)", "Plasmablast (markers)": "Plasmablast", "MS1 monocyte (IL1R2+)": "MS1 mono",
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+ "Cycling monocyte (Ye 2026)": "Cycling mono", "ISG-high monocyte (positive control)": "ISG-high mono",
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+ "ISG-high T": "ISG-high T", "DN2 / ABC B": "DN2 / ABC B", "HSPC": "HSPC", "Cytotoxic CD4 T": "Cytotoxic CD4 T",
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+ "Granulocyte-like (LDG)": "Granulocyte-like"}
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+
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+
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+ def load():
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+ s = pd.read_csv(SRC / "summary.csv")
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+ c = pd.read_csv(SRC / "contrasts.csv")
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+ s = s[~s.state.str.contains(NEG, case=False)]
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+ c = c[~c.state.str.contains(NEG, case=False)]
61
+ s["log2_ratio"] = np.log2(s.gen_over_obs.where(s.gen_over_obs > 0))
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+ # judgeable state x cohort pairs: from the LoRA arm's observed side (identical cells in every arm)
63
+ ref = s[s.arm.isin(["lora5", "real_lora__raw"])]
64
+ ok = ref.groupby(["dataset", "state"]).agg(obs=("obs_state_native", "min"), don=("donors_with_state_obs", "min"))
65
+ keep = ok[(ok.obs >= MIN_OBS) & (ok.don >= MIN_DONORS)].index
66
+ s = s.set_index(["dataset", "state"]).loc[lambda d: d.index.isin(keep)].reset_index()
67
+ c = c.set_index(["dataset", "state"]).loc[lambda d: d.index.isin(keep)].reset_index()
68
+ return s, c, list(keep)
69
+
70
+
71
+ def agg_few(s, c):
72
+ f = s[s.design == "fewpair"]
73
+ a = f.groupby(["dataset", "state", "arm"]).agg(log2_ratio=("log2_ratio", "mean"), spearman=("spearman_donors", "mean"),
74
+ auroc=("auroc_high_low", "mean")).reset_index()
75
+ d = c[c.design == "fewpair"].groupby(["dataset", "state", "arm"]).same_direction.mean().rename("direction").reset_index()
76
+ return a.merge(d, on=["dataset", "state", "arm"], how="left")
77
+
78
+
79
+ def agg_pool(s, c):
80
+ f = s[s.design == "fivefold"][["dataset", "state", "arm", "log2_ratio", "spearman_donors", "auroc_high_low"]]
81
+ f = f.rename(columns={"spearman_donors": "spearman", "auroc_high_low": "auroc"})
82
+ d = c[c.design == "fivefold"][["dataset", "state", "arm", "same_direction"]].rename(columns={"same_direction": "direction"})
83
+ d["direction"] = d.direction.astype(float)
84
+ return f.merge(d, on=["dataset", "state", "arm"], how="left")
85
+
86
+
87
+ def dotplot(ax, tab, keys, arms, col, xlab, band=None, xlim=None, ref=None):
88
+ y = np.arange(len(keys))
89
+ for i, (ds, st) in enumerate(keys):
90
+ if i % 2 == 0:
91
+ ax.axhspan(i - 0.5, i + 0.5, color="#F4F4F4", zorder=0)
92
+ if band:
93
+ ax.axvspan(*band, color="#E6E6E6", zorder=0)
94
+ if ref is not None:
95
+ ax.axvline(ref, color=ST.INK, lw=0.8)
96
+ for k, (arm, _l, c, mk) in enumerate(arms):
97
+ v = [tab[(tab.dataset == ds) & (tab.state == st) & (tab.arm == arm)][col] for ds, st in keys]
98
+ v = [float(x.iloc[0]) if len(x) else np.nan for x in v]
99
+ ax.scatter(v, y + (k - 1) * 0.18, s=46 if arm.startswith(("lora", "real_lora")) else 34, marker=mk, color=c,
100
+ edgecolor=ST.INK, lw=0.5, zorder=3)
101
+ ax.set_yticks(y, [f"{NAME[ds]} · {SHORT.get(st, st)}" for ds, st in keys], fontsize=ST.FS - 5)
102
+ ax.set_ylim(len(keys) - 0.5, -0.5)
103
+ if xlim:
104
+ ax.set_xlim(*xlim)
105
+ ax.set_xlabel(xlab, fontsize=ST.FS - 3)
106
+ ax.tick_params(axis="x", labelsize=ST.FS - 4)
107
+ ax.grid(axis="x", color="#E3E3E3", linewidth=0.8)
108
+
109
+
110
+ def counts(tab, keys, a_lora, a_sc):
111
+ """per metric: states where LoRA is better than scSemiProfiler (and within 2-fold for the fraction)"""
112
+ t = tab.set_index(["dataset", "state", "arm"])
113
+ out = {"n": len(keys)}
114
+ g = lambda ds, st, a, m: float(t.loc[(ds, st, a), m]) if (ds, st, a) in t.index else np.nan # noqa: E731
115
+ err = lambda k, a: abs(g(*k, a, "log2_ratio")) if np.isfinite(g(*k, a, "log2_ratio")) else np.inf # noqa: E731
116
+ rho = lambda k, a: g(*k, a, "spearman") if np.isfinite(g(*k, a, "spearman")) else -np.inf # noqa: E731
117
+ # a state a method never generates has no ratio / rank: it counts as that method's miss
118
+ out["frac_closer"] = sum(err(k, a_lora) < err(k, a_sc) for k in keys)
119
+ out["within2_lora"] = sum(err(k, a_lora) <= 1 for k in keys)
120
+ out["within2_sc"] = sum(err(k, a_sc) <= 1 for k in keys)
121
+ out["not_generated_lora"] = sum(not np.isfinite(g(*k, a_lora, "log2_ratio")) for k in keys)
122
+ out["not_generated_sc"] = sum(not np.isfinite(g(*k, a_sc, "log2_ratio")) for k in keys)
123
+ out["rho_better"] = sum(rho(k, a_lora) > rho(k, a_sc) for k in keys)
124
+ out["rho_median_lora"] = float(np.nanmedian([g(*k, a_lora, "spearman") for k in keys]))
125
+ out["rho_median_sc"] = float(np.nanmedian([g(*k, a_sc, "spearman") for k in keys]))
126
+ out["dir_lora"] = float(np.nanmean([g(*k, a_lora, "direction") for k in keys]))
127
+ out["dir_sc"] = float(np.nanmean([g(*k, a_sc, "direction") for k in keys]))
128
+ return out
129
+
130
+
131
+ def main() -> int:
132
+ s, c, keys = load()
133
+ fa, pa = agg_few(s, c), agg_pool(s, c)
134
+ keys = sorted(keys, key=lambda k: (list(NAME).index(k[0]), k[1]))
135
+ pd.concat([fa.assign(design="5 donors (mean of 5 draws)"), pa.assign(design="5-fold pooled")]).to_csv(
136
+ DAT / "fig5_rare_states.csv", index=False, float_format="%.5g")
137
+ leg = lambda arms: [Line2D([0], [0], marker=mk, ls="none", color=c, mec=ST.INK, mew=0.5, ms=8) # noqa: E731
138
+ for _a, _l, c, mk in arms]
139
+ COH = {"ye2026_sepsis": "#CC79A7", "imperial_eskd": "#0072B2", "giroux2022": "#009E73", "ji2025_chili": "#E69F00"}
140
+ KEY = [("ye2026_sepsis", "MS1 monocyte (IL1R2+)"), ("ye2026_sepsis", "Plasmablast (label)"),
141
+ ("ye2026_sepsis", "ISG-high T"), ("imperial_eskd", "MS1 monocyte (IL1R2+)"),
142
+ ("imperial_eskd", "Plasmablast (label)"), ("imperial_eskd", "ISG-high T"), ("imperial_eskd", "Cycling T/NK"),
143
+ ("ji2025_chili", "MS1 monocyte (IL1R2+)"), ("ji2025_chili", "ISG-high T"), ("giroux2022", "Cycling T/NK")]
144
+ KEY = [k for k in KEY if k in keys]
145
+ MISS = 11.5 # where 'not generated' is drawn on the |log2| axis
146
+
147
+ def scatter(ax, tab, a_x, a_y, col, lab, lim, miss=None, within=False):
148
+ t = tab.set_index(["dataset", "state", "arm"])[col]
149
+ for ds, st in keys:
150
+ x, y = t.get((ds, st, a_x), np.nan), t.get((ds, st, a_y), np.nan)
151
+ if col == "log2_ratio":
152
+ x = abs(x) if np.isfinite(x) else miss
153
+ y = abs(y) if np.isfinite(y) else miss
154
+ elif not (np.isfinite(x) and np.isfinite(y)):
155
+ x = x if np.isfinite(x) else lim[0] + 0.03
156
+ y = y if np.isfinite(y) else lim[0] + 0.03
157
+ ax.scatter(x, y, s=34, color=COH[ds], edgecolor=ST.INK, lw=0.4, zorder=3)
158
+ ax.plot(lim, lim, color=ST.INK, lw=0.8, zorder=1)
159
+ if within:
160
+ ax.axhspan(lim[0], 1, color="#F6DCC8", zorder=0)
161
+ ax.text(lim[1] * 0.98, 0.5, "LoRA within 2-fold", ha="right", va="center", fontsize=ST.FS - 5, color=ST.SUBINK)
162
+ if miss is None and col != "log2_ratio":
163
+ ax.axvline(lim[0] + 0.08, color=ST.GREY, ls=":", lw=1)
164
+ ax.text(lim[0] + 0.03, lim[1] * 0.98, "not\ngenerated", ha="left", va="top", fontsize=ST.FS - 6,
165
+ color=ST.SUBINK, rotation=0)
166
+ if miss is not None:
167
+ ax.axvline(miss - 0.5, color=ST.GREY, ls=":", lw=1)
168
+ ax.text(miss, lim[1] * 0.98, "not\ngenerated", ha="center", va="top", fontsize=ST.FS - 6, color=ST.SUBINK)
169
+ ax.set_xlim(*lim)
170
+ ax.set_ylim(*lim)
171
+ ax.set_aspect("equal")
172
+ ax.set_title(lab, fontsize=ST.FS - 1, loc="left")
173
+ ax.grid(color="#EEEEEE", linewidth=0.8)
174
+ ax.tick_params(labelsize=ST.FS - 4)
175
+
176
+ coh_leg = [Line2D([0], [0], marker="o", ls="none", color=c, mec=ST.INK, mew=0.4, ms=7) for c in COH.values()]
177
+ # A: fraction
178
+ fig, (a1, a2) = plt.subplots(1, 2, figsize=ST.FULL, gridspec_kw={"wspace": 0.55, "width_ratios": [1, 1.25]})
179
+ scatter(a1, fa, "scsemi5", "lora5", "log2_ratio", "Fraction error, |log2(gen / obs)|", (0, 12.2), miss=MISS, within=True)
180
+ a1.set_xlabel("scSemiProfiler, 5 donors", fontsize=ST.FS - 3)
181
+ a1.set_ylabel("PBISC LoRA, 5 donors", fontsize=ST.FS - 3)
182
+ dotplot(a2, fa, KEY, FEW, "log2_ratio", "log2(generated / observed); band = within 2-fold", band=(-1, 1), xlim=(-8, 3), ref=0)
183
+ a2.set_title("Disease states", fontsize=ST.FS - 1, loc="left")
184
+ fig.legend(coh_leg + leg(FEW), [NAME[d] for d in COH] + [l for _a, l, _c, _m in FEW], loc="lower center", ncol=7,
185
+ bbox_to_anchor=(0.5, -0.09), fontsize=ST.FS - 5)
186
+ ST.save(fig, "fig5_rare_fraction", FIG)
187
+ # B: donors and direction
188
+ fig, (a1, a2) = plt.subplots(1, 2, figsize=ST.FULL, gridspec_kw={"wspace": 0.45, "width_ratios": [1, 1.1]})
189
+ scatter(a1, fa, "scsemi5", "lora5", "spearman", "Donor ranking, Spearman ρ", (-0.5, 1.0))
190
+ a1.set_xlabel("scSemiProfiler, 5 donors", fontsize=ST.FS - 3)
191
+ a1.set_ylabel("PBISC LoRA, 5 donors", fontsize=ST.FS - 3)
192
+ dirs = {a: float(fa[fa.arm == a].direction.mean()) for a, *_ in FEW}
193
+ for i, (a, l, c, _m) in enumerate(FEW):
194
+ a2.barh(i, dirs[a], 0.6, color=c, edgecolor="none")
195
+ a2.text(dirs[a] + 0.01, i, f"{100 * dirs[a]:.0f}%", va="center", fontsize=ST.FS - 4, color=ST.SUBINK)
196
+ a2.axvline(0.5, color=ST.GREY, ls=":", lw=1)
197
+ a2.set_yticks(range(len(FEW)), [l for _a, l, _c, _m in FEW], fontsize=ST.FS - 4)
198
+ a2.set_ylim(len(FEW) - 0.4, -0.6)
199
+ a2.set_xlim(0, 1)
200
+ a2.set_title("Disease direction kept (states x draws)", fontsize=ST.FS - 1, loc="left")
201
+ a2.tick_params(axis="y", length=0)
202
+ fig.legend(coh_leg, [NAME[d] for d in COH], loc="lower center", ncol=4, bbox_to_anchor=(0.3, -0.08), fontsize=ST.FS - 4)
203
+ ST.save(fig, "fig5_rare_donors", FIG)
204
+ # C: five-fold
205
+ fig, (a1, a2) = plt.subplots(1, 2, figsize=ST.FULL, gridspec_kw={"wspace": 0.35})
206
+ scatter(a1, pa, "scsemi__raw", "real_lora__raw", "log2_ratio", "Fraction error, |log2(gen / obs)|", (0, 12.2),
207
+ miss=MISS, within=True)
208
+ scatter(a2, pa, "scsemi__raw", "real_lora__raw", "spearman", "Donor ranking, Spearman ρ", (-0.5, 1.0))
209
+ for a in (a1, a2):
210
+ a.set_xlabel("scSemiProfiler, same pairs", fontsize=ST.FS - 3)
211
+ a.set_ylabel("PBISC LoRA", fontsize=ST.FS - 3)
212
+ fig.legend(coh_leg, [NAME[d] for d in COH], loc="lower center", ncol=4, bbox_to_anchor=(0.5, -0.08), fontsize=ST.FS - 4)
213
+ ST.save(fig, "fig5_rare_fivefold", FIG)
214
+ vs_zs = {m: sum((abs(fa[(fa.dataset == d) & (fa.state == st) & (fa.arm == "lora5")].log2_ratio.iloc[0])
215
+ < abs(fa[(fa.dataset == d) & (fa.state == st) & (fa.arm == "zs_raw")].log2_ratio.iloc[0]))
216
+ if m == "frac" else
217
+ (fa[(fa.dataset == d) & (fa.state == st) & (fa.arm == "lora5")].spearman.iloc[0]
218
+ > fa[(fa.dataset == d) & (fa.state == st) & (fa.arm == "zs_raw")].spearman.iloc[0])
219
+ for d, st in keys) for m in ("frac", "rho")}
220
+
221
+ cf, cp = counts(fa, keys, "lora5", "scsemi5"), counts(pa, keys, "real_lora__raw", "scsemi__raw")
222
+ n = cf["n"]
223
+ rule = (f"State × cohort pairs with ≥ {MIN_OBS} observed state cells in ≥ {MIN_DONORS} donors (native depth); "
224
+ "negative control left out. Marker rules from the literature (plans/rare_states_screen_20261004/tools/"
225
+ "states.json); observed parent cells thinned to the generated depth; labels = the benchmark's frozen "
226
+ "scANVI calls; the benchmark's Poisson read-out reproduced cell by cell. ")
227
+ slides = [
228
+ {"title": "Rare states with 5 pairs: how many cells", "figure": "fig5_rare_fraction",
229
+ "keywords": [f"Within 2-fold: LoRA-5 {cf['within2_lora']}/{n}, scSemiProfiler-5 {cf['within2_sc']}/{n}",
230
+ f"Closer to the observed fraction than scSemiProfiler-5: {cf['frac_closer']}/{n}",
231
+ "Rare states kept, not averaged away"],
232
+ "short": "4 paired disease cohorts; 5 donors, mean of 5 draws. 0 = observed fraction; band = within 2-fold.",
233
+ "full": ("Main comparison: 5 donors per draw (LoRA-5 vs scSemiProfiler with the same 5 donors as representatives, "
234
+ "and zero-shot), every other usable sample tested, mean over 5 draws of log2(generated % / observed %) "
235
+ "of the state within its parent type. Left: one point per state x cohort; below the diagonal = LoRA-5 "
236
+ f"closer; states a method never generates are drawn as 'not generated' (scSemiProfiler-5: "
237
+ f"{cf['not_generated_sc']} of {n}; LoRA-5: {cf['not_generated_lora']}). Zero-shot (no pairs) is "
238
+ f"closer than LoRA-5 on {n - vs_zs['frac']} of {n} fractions, LoRA-5 ranks donors better on "
239
+ f"{vs_zs['rho']} of {n}. " + rule + "Source: data/fig5_rare_states.csv "
240
+ "(plans/rare_states_paired_20261008/out/summary.csv).")},
241
+ {"title": "Rare states with 5 pairs: in the right donors", "figure": "fig5_rare_donors",
242
+ "keywords": [f"Donor ranking: median ρ {cf['rho_median_lora']:.2f} vs {cf['rho_median_sc']:.2f} (scSemiProfiler-5)",
243
+ f"Better donor ranking than scSemiProfiler-5: {cf['rho_better']}/{n}",
244
+ f"Disease direction kept: {100 * cf['dir_lora']:.0f}% vs {100 * cf['dir_sc']:.0f}% of draws"],
245
+ "short": "Spearman over donors of generated vs observed state %; direction = case-vs-control sign.",
246
+ "full": ("Main comparison (5 donors, 5 draws). Left: Spearman over the tested donors of the generated vs observed "
247
+ "(thinned) state percentage, mean over draws. Right: share of draws where the case-vs-control difference "
248
+ "of donor means has the observed sign (sepsis vs controls, COVID+ vs COVID-, severe vs mild, ChILI vs "
249
+ "controls). " + rule + "Source: data/fig5_rare_states.csv (out/summary.csv, out/contrasts.csv).")},
250
+ {"title": "5-fold CV: rare states", "figure": "fig5_rare_fivefold",
251
+ "keywords": [f"Within 2-fold: LoRA {cp['within2_lora']}/{n}, scSemiProfiler {cp['within2_sc']}/{n}",
252
+ f"Donor ranking: median ρ {cp['rho_median_lora']:.2f} vs {cp['rho_median_sc']:.2f}",
253
+ f"Better donor ranking: {cp['rho_better']}/{n}"],
254
+ "short": "Donor-level 5-fold CV, pooled; reported separately from the 5-pair comparison.",
255
+ "full": ("Reported separately: 5-fold CV, every sample generated by the fold model that never trained on it; "
256
+ "scSemiProfiler with exactly LoRA's training pairs as representatives. " + rule
257
+ + "Source: data/fig5_rare_states.csv.")}]
258
+ out_slides = []
259
+ for sl in slides:
260
+ if len(sl["short"]) > 110:
261
+ raise SystemExit(f"short footnote too long: {sl['title']}")
262
+ out_slides.append({"title": sl["title"], "layout": "full", "figures": [str(FIG / f"{sl['figure']}.png")],
263
+ "keywords": sl["keywords"], "footnote_short": sl["short"], "footnote": sl["full"],
264
+ "numbers": [{"value": json.dumps({"5 donors": cf, "5-fold": cp}), "source": "data/fig5_rare_states.csv"}]})
265
+ (DAT / "fig5_rare_states_slide_text.json").write_text(json.dumps(
266
+ {"section": "fig5-rare", "scripts": [str(Path(__file__).resolve())],
267
+ "generated_from": "tools/fig5_rare_states.py (rerun to refresh; do not edit by hand)", "slides": out_slides},
268
+ indent=1, ensure_ascii=False))
269
+ print(f"{len(keys)} state x cohort pairs")
270
+ print(json.dumps({"5 donors": cf, "5-fold": cp}, indent=1))
271
+ for sl in out_slides:
272
+ print(sl["title"], "|", " | ".join(sl["keywords"]))
273
+ return 0
274
+
275
+
276
+ if __name__ == "__main__":
277
+ sys.exit(main())
paper-releases/pbisc-diffusion/updates/20261008T125804Z-deck-fig2-3-healthy-fig5-rare/diffusion/dataset/server_1/model8/presentations/2026-09-30--paper-summary--r00/tools/sec10_paired_subset_cohorts.py ADDED
@@ -0,0 +1,448 @@
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1
+ """Section 10 (planned): cohorts that have a paired bulk-sc subset plus bulk-only samples.
2
+
3
+ Counts only; no new model output. Every number is read from the pairing manifests / tables below.
4
+ Outputs
5
+ data/sec10_cohort_counts.csv one row per cohort (samples, donors, flags, LoRA status, sources)
6
+ data/sec10_bulk_only_groups.csv paired-usable vs bulk-only samples per clinical group
7
+ data/sec10_quoted_numbers.csv every number on the slide with its source
8
+ figures/sec10_paired_subset_cohorts.png/.pdf
9
+ """
10
+ import json
11
+ import re
12
+ import sys
13
+ from collections import Counter
14
+ from pathlib import Path
15
+
16
+ import numpy as np
17
+ import pandas as pd
18
+
19
+ DECK = Path("/home/sj_server_1/PBISC/immun-pbmc-fm/model_8_sparse_data_diffusion/presentations/2026-09-30--paper-summary--r00")
20
+ sys.path.insert(0, str(DECK / "tools"))
21
+ import style # noqa: E402
22
+ import matplotlib.pyplot as plt # noqa: E402
23
+ from matplotlib.patches import Patch # noqa: E402
24
+
25
+ FIG = DECK / "figures"
26
+ DATA = DECK / "data"
27
+ PFT = Path("/home/sj_server_1/PBISC/immun-pbmc-fm/model_8_sparse_data_diffusion/plans/paired_finetune_intradataset_20260927")
28
+ PF = PFT / "data"
29
+ SCORES = PFT / "scores"
30
+ GEN = PFT / "generated"
31
+ US = Path("/home/sj_server_1/PBISC/immun-pbmc-fm/model_8_sparse_data_diffusion/plans/utility_studies_final6k_20260925")
32
+ IMPERIAL_HTSEQ = Path("/home/sj_server_1/gblee/datalake/paired-pbmc-bulk-sc/datasets/Zenodo_6497251/raw/htseq_counts.csv")
33
+ JI_SC_LIBS = Path("/home/sj_server_1/gblee/datalake/paired-pbmc-bulk-sc/processing/ji2025_chili_v1_20260928/pairing/"
34
+ "sc_gex_libraries_with_bulk_match.csv")
35
+
36
+ rows, groups, quoted = [], [], []
37
+
38
+
39
+ def q(item, value, source):
40
+ quoted.append(dict(item=item, value=value, source=str(source)))
41
+
42
+
43
+ def add_groups(cohort, paired_usable_by_group, bulk_only_by_group, src):
44
+ for g in sorted(set(paired_usable_by_group) | set(bulk_only_by_group)):
45
+ groups.append(dict(cohort=cohort, group=g,
46
+ paired_usable=int(paired_usable_by_group.get(g, 0)),
47
+ bulk_only=int(bulk_only_by_group.get(g, 0)), source=src))
48
+
49
+
50
+ def excl_breakdown(pairs, usable_mask):
51
+ """Why paired rows are excluded: identity fail / borderline, or identity pass but <200 cells."""
52
+ ex = pairs[~usable_mask]
53
+ kind = ex.identity_check.str.split(":").str[0].str.strip()
54
+ c = Counter(kind)
55
+ c["below_200_cells_only"] = int((kind == "pass").sum())
56
+ c.pop("pass", None)
57
+ return dict(c)
58
+
59
+
60
+ def lora_status(ds):
61
+ """5-fold LoRA composition L1 (fold mean) and the leave-one-out composition null from AGGREGATE."""
62
+ agg = json.load(open(SCORES / ds / "aggregate.json"))
63
+ md = (SCORES / ds / "AGGREGATE.md").read_text()
64
+ null = float(re.search(r"Leave-one-out composition null \(fold mean\): ([0-9.]+)", md).group(1))
65
+ lora = agg["arms"]["real_lora__raw"]
66
+ assert lora["n_folds"] == 5
67
+ return lora["comp_l1"]["mean"], null, agg["contrast"]["real_lora__raw"], agg["contrast"]["zs__raw"]
68
+
69
+
70
+ def no_bulk_only_generation(ds, n_paired_usable):
71
+ """PLANNED check: nothing generated for this cohort's bulk-only samples (file names + pooled manifests)."""
72
+ names = [p.name.lower() for p in (GEN / ds).rglob("*")]
73
+ assert not [n for n in names if "bulkonly" in n or "bulk_only" in n], f"{ds}: bulk-only generation exists"
74
+ pm = GEN / ds / "pooled" / "POOL_MANIFEST.json"
75
+ if pm.exists():
76
+ for arm, v in json.load(open(pm))["arms"].items():
77
+ assert v["n_samples"] <= n_paired_usable, (ds, arm, v["n_samples"])
78
+ return True
79
+
80
+
81
+ # ---------------- Ye 2026 sepsis (GSE279448 bulk / GSE279452 sc) ----------------
82
+ ds = "ye2026_sepsis"
83
+ d = PF / ds
84
+ man = json.load(open(d / "MANIFEST.json"))
85
+ pairs = pd.read_csv(d / "pairs.csv")
86
+ bulk_all = pd.read_csv(d / "identity_sex_bulk_all.csv")
87
+ bulk_only = man["excluded"]["bulk_samples_without_sc"]
88
+ assert len(pairs) == man["rows"]
89
+ assert len(pairs) + len(bulk_only) == len(bulk_all), "Ye: paired + bulk-only != all bulks"
90
+ umask = pairs.identity_pass.astype(bool)
91
+ usable = pairs[umask]
92
+ ye_map_bo = {"Adult Sepsis": "sepsis", "Adult Healthy Control": "control", "Adult ICU Control": "control",
93
+ "Pediatric ICU Control": "control", "Pediatric Sepsis": "sepsis",
94
+ "Pediatric Healthy Control": "control"}
95
+ bo_raw = Counter(x["ch_group"] for x in bulk_only)
96
+ assert set(bo_raw) <= set(ye_map_bo), bo_raw
97
+ bo_grp = Counter()
98
+ for k, v in bo_raw.items():
99
+ bo_grp[ye_map_bo[k]] += v
100
+ pu_grp = Counter("sepsis" if "sepsis" in g else "control" for g in usable.group)
101
+ bo_ids = {x["sample_id"] for x in bulk_only}
102
+ flag_list = man["findings"]["sex_vs_geo"]["bulk_all_samples_discordant_or_ambiguous"]
103
+ ye_flag_bo = sorted(x["sample_id"] for x in flag_list if x["sample_id"] in bo_ids)
104
+ assert len(ye_flag_bo) == len(flag_list), "Ye: a sex-flagged bulk is paired"
105
+ paired_don, usable_don = set(pairs.donor_id), set(usable.donor_id)
106
+ comp, null, c_lora, c_zs = lora_status(ds)
107
+ no_bulk_only_generation(ds, len(usable))
108
+ add_groups("Ye 2026 sepsis", pu_grp, bo_grp, f"{d/'MANIFEST.json'} (excluded.bulk_samples_without_sc); {d/'pairs.csv'}")
109
+ rows.append(dict(
110
+ cohort="Ye 2026 sepsis", specimen="PBMC bulk",
111
+ bulk_total=len(bulk_all), paired=len(pairs), seg_train=len(usable), seg_nocomp=0,
112
+ seg_excl=len(pairs) - len(usable), excl_why=json.dumps(excl_breakdown(pairs, umask)), bulk_only=len(bulk_only),
113
+ donors_bulk_total=len(bulk_all), # one sample per donor (QC_REPORT: donor = sample)
114
+ donors_paired_usable=len(usable_don), donors_bulk_only=len(bo_ids), donors_excl_only=len(paired_don - usable_don),
115
+ bulk_only_groups=f"{bo_grp['sepsis']} sepsis, {bo_grp['control']} control",
116
+ sex_flag_bulk_only=len(ye_flag_bo), sex_flag_ids=";".join(ye_flag_bo),
117
+ lora_cv="5-fold", lora_comp_l1=comp, comp_null=null,
118
+ lora_logfc_r=c_lora["r_generated"], zs_raw_logfc_r=c_zs["r_generated"],
119
+ extra=f"controls: paired QC pass {pu_grp['control']} + bulk-only {bo_grp['control']}",
120
+ usable_rule="identity_pass",
121
+ source=f"{d/'MANIFEST.json'}; {d/'pairs.csv'}; {d/'identity_sex_bulk_all.csv'}; {SCORES/ds/'aggregate.json'}; "
122
+ f"{SCORES/ds/'AGGREGATE.md'}",
123
+ ))
124
+ ye_controls_paired, ye_controls_bulk_only = pu_grp["control"], bo_grp["control"]
125
+ q("Sepsis controls, paired QC pass", ye_controls_paired, d / "pairs.csv")
126
+ q("Sepsis controls, bulk-only (36 adult HC + 17 adult ICU + 1 ped ICU)", ye_controls_bulk_only,
127
+ f"{d/'MANIFEST.json'} excluded.bulk_samples_without_sc ch_group")
128
+
129
+ # ---------------- Imperial ESKD COVID (Zenodo 6497251 bulk / COVID-19 Cell Atlas sc) ----------------
130
+ ds = "imperial_eskd"
131
+ d = PF / ds
132
+ man = json.load(open(d / "MANIFEST.json"))
133
+ pairs = pd.read_csv(d / "pairs.csv")
134
+ with open(IMPERIAL_HTSEQ) as fh: # header only; the matrix is never loaded
135
+ header = [c.strip().strip('"') for c in fh.readline().rstrip("\n").split(",")]
136
+ bulk_cols = header[1:]
137
+ assert header[0] == "gencode_id"
138
+ bulk_only = man["excluded"]["bulk_samples_without_sc"]
139
+ assert len(pairs) + len(bulk_only) == len(bulk_cols), "Imperial: paired + bulk-only != htseq columns"
140
+ assert set(pairs.bulk_sample) | {x["bulk_sample"] for x in bulk_only} == set(bulk_cols)
141
+ umask = pairs.identity_pass.astype(bool) & ~pairs.below_200_cells.astype(bool)
142
+ usable = pairs[umask]
143
+ pid = lambda s: s.split("_")[0] # noqa: E731 column names are <patient>_<status>[_<day>]
144
+ bulk_pat = {pid(c) for c in bulk_cols}
145
+ paired_pat, usable_pat = set(pairs.donor_id), set(usable.donor_id)
146
+ assert paired_pat <= bulk_pat
147
+ sexb = pd.read_csv(d / "identity_sex_bulk_all.csv")
148
+ assert set(sexb.donor_id) == bulk_pat and len(sexb) == len(bulk_cols)
149
+ bo_sex = sexb[~sexb.paired.astype(bool)]
150
+ imp_flag = bo_sex[(bo_sex.bulk_sex_call == "ambiguous")
151
+ | (bo_sex.bulk_sex_call.str[0].str.upper() != bo_sex.sex_meta.str.upper())]
152
+ bo_grp = Counter({"covid_positive": 0, "covid_negative": 0, "recovery": 0})
153
+ for x in bulk_only:
154
+ bo_grp[{"positive": "covid_positive", "negative": "covid_negative", "recovery": "recovery"}[x["status"]]] += 1
155
+ pu_grp = Counter(usable.group)
156
+ comp, null, c_lora, c_zs = lora_status(ds)
157
+ no_bulk_only_generation(ds, len(usable))
158
+ add_groups("Imperial ESKD COVID", pu_grp, bo_grp, f"{d/'MANIFEST.json'} (excluded.bulk_samples_without_sc); {d/'pairs.csv'}")
159
+ rows.append(dict(
160
+ cohort="Imperial ESKD COVID", specimen="PBMC bulk, longitudinal",
161
+ bulk_total=len(bulk_cols), paired=len(pairs), seg_train=len(usable), seg_nocomp=0,
162
+ seg_excl=len(pairs) - len(usable), excl_why=json.dumps(excl_breakdown(pairs, umask)), bulk_only=len(bulk_only),
163
+ donors_bulk_total=len(bulk_pat),
164
+ donors_paired_usable=len(usable_pat), donors_bulk_only=len(bulk_pat - paired_pat),
165
+ donors_excl_only=len(paired_pat - usable_pat),
166
+ bulk_only_groups=f"{bo_grp['covid_positive']} COVID+, {bo_grp['covid_negative']} COVID−, "
167
+ f"{bo_grp['recovery']} recovery",
168
+ sex_flag_bulk_only=len(imp_flag), sex_flag_ids=";".join(imp_flag.bulk_sample),
169
+ lora_cv="5-fold", lora_comp_l1=comp, comp_null=null,
170
+ lora_logfc_r=c_lora["r_generated"], zs_raw_logfc_r=c_zs["r_generated"],
171
+ extra="donors excluded-only: " + ";".join(sorted(paired_pat - usable_pat)),
172
+ usable_rule="identity_pass and not below_200_cells",
173
+ source=f"{d/'MANIFEST.json'}; {d/'pairs.csv'}; {d/'identity_sex_bulk_all.csv'}; header of {IMPERIAL_HTSEQ}; "
174
+ f"{SCORES/ds/'aggregate.json'}; {SCORES/ds/'AGGREGATE.md'}",
175
+ ))
176
+
177
+ # ---------------- Ji 2025 ChILI (GSE287540 bulk = PAXgene whole blood / GSE287541 sc) ----------------
178
+ ds = "ji2025_chili"
179
+ d = PF / ds
180
+ man = json.load(open(d / "MANIFEST.json"))
181
+ pairs = pd.read_csv(d / "pairs.csv")
182
+ bulk_all = pd.read_csv(d / "identity_sex_bulk_all.csv")
183
+ bulk_only = man["excluded"]["bulk_samples_without_sc"]
184
+ assert len(pairs) + len(bulk_only) == len(bulk_all), "Ji: paired + bulk-only != all bulks"
185
+ assert "whole blood" in json.dumps(man["specimen_warning"]).lower()
186
+ umask = pairs.identity_pass.astype(bool)
187
+ usable = pairs[umask]
188
+ norm = lambda s: "N%03d" % int(re.match(r"N0*(\d+)", s).group(1)) # noqa: E731 N87 == N087
189
+ bulk_pat = {norm(s) for s in bulk_all.sample_id}
190
+ paired_pat, usable_pat = {norm(s) for s in pairs.donor_id}, {norm(s) for s in usable.donor_id}
191
+ assert paired_pat <= bulk_pat
192
+ bo_gsm = {x["gsm"] for x in bulk_only}
193
+ bo_raw = Counter(x["Sample_title"].split("_", 1)[1] for x in bulk_only) # e.g. chili_BC, control_AC
194
+ bo_grp = Counter()
195
+ for k, v in bo_raw.items():
196
+ bo_grp["ChILI" if k.startswith("chili") else "control"] += v
197
+ pu_grp = Counter("ChILI" if o == "ChILI" else "control" for o in usable.outcome)
198
+ chili_bc_bulk_only = int(bo_raw.get("chili_BC", 0))
199
+ chili_bc_paired = int(man["pairs_by_outcome_timepoint"].get("ChILI_BC", 0))
200
+ flag = bulk_all[bulk_all.sex_discordant_with_geo.astype(bool) | (bulk_all.bulk_sex_call == "ambiguous")]
201
+ assert set(flag.bulk_gsm) <= bo_gsm, "Ji: a sex-flagged bulk is paired"
202
+ ji_flag_bo = sorted(flag.sample_id)
203
+ ji_flag_bc = [s for s in ji_flag_bo if s.endswith("_chili_BC")]
204
+ sclib = pd.read_csv(JI_SC_LIBS)
205
+ ji_bc_sc_unpaired = sclib[(sclib.outcome == "ChILI") & (sclib.timepoint == "BC") & ~sclib.paired.astype(bool)]
206
+ comp, null, c_lora, c_zs = lora_status(ds)
207
+ no_bulk_only_generation(ds, len(usable))
208
+ add_groups("Ji 2025 ChILI", pu_grp, bo_grp, f"{d/'MANIFEST.json'} (excluded.bulk_samples_without_sc); {d/'pairs.csv'}")
209
+ for k in sorted(bo_raw):
210
+ groups.append(dict(cohort="Ji 2025 ChILI", group="detail:" + k, paired_usable=int(
211
+ ((usable.outcome == ("ChILI" if k.startswith("chili") else "control")) & (usable.timepoint == k.split("_")[1])).sum()),
212
+ bulk_only=int(bo_raw[k]), source=str(d / "MANIFEST.json")))
213
+ rows.append(dict(
214
+ cohort="Ji 2025 ChILI", specimen="whole-blood bulk",
215
+ bulk_total=len(bulk_all), paired=len(pairs), seg_train=len(usable), seg_nocomp=0,
216
+ seg_excl=len(pairs) - len(usable), excl_why=json.dumps(excl_breakdown(pairs, umask)), bulk_only=len(bulk_only),
217
+ donors_bulk_total=len(bulk_pat),
218
+ donors_paired_usable=len(usable_pat), donors_bulk_only=len(bulk_pat - paired_pat),
219
+ donors_excl_only=len(paired_pat - usable_pat),
220
+ bulk_only_groups=f"{bo_grp['ChILI']} ChILI ({chili_bc_bulk_only} pre-ICI), {bo_grp['control']} control",
221
+ sex_flag_bulk_only=len(ji_flag_bo), sex_flag_ids=";".join(ji_flag_bo),
222
+ lora_cv="5-fold", lora_comp_l1=comp, comp_null=null,
223
+ lora_logfc_r=c_lora["r_generated"], zs_raw_logfc_r=c_zs["r_generated"],
224
+ extra=(f"ChILI before ICI (BC): paired {chili_bc_paired}, bulk-only {chili_bc_bulk_only} "
225
+ f"({len(ji_flag_bc)} sex-flagged: {';'.join(ji_flag_bc)}), unpaired ChILI BC sc libraries "
226
+ f"{len(ji_bc_sc_unpaired)} ({';'.join(ji_bc_sc_unpaired.sample_id)}); donors excluded-only: "
227
+ + ";".join(sorted(paired_pat - usable_pat))),
228
+ usable_rule="identity_pass",
229
+ source=f"{d/'MANIFEST.json'}; {d/'pairs.csv'}; {d/'identity_sex_bulk_all.csv'}; {JI_SC_LIBS}; "
230
+ f"{SCORES/ds/'aggregate.json'}; {SCORES/ds/'AGGREGATE.md'}",
231
+ ))
232
+ q("ChILI before ICI (BC), bulk-only", chili_bc_bulk_only, f"{d/'MANIFEST.json'} excluded.bulk_samples_without_sc Sample_title")
233
+ q("ChILI before ICI (BC), paired", chili_bc_paired, f"{d/'MANIFEST.json'} pairs_by_outcome_timepoint")
234
+ q("ChILI before ICI (BC), unpaired sc libraries (patients absent from bulk)", len(ji_bc_sc_unpaired), JI_SC_LIBS)
235
+ q("ChILI before ICI (BC), bulk-only sex-flagged", len(ji_flag_bc), f"{d/'identity_sex_bulk_all.csv'} sex_discordant_with_geo")
236
+
237
+ # ---------------- Arunachalam 2020 COVID (GSE152418 bulk / GSE155673 sc) ----------------
238
+ meta = US / "arunachalam" / "metadata"
239
+ bc = pd.read_csv(meta / "bulk_cohort.csv")
240
+ rec = pd.read_csv(meta / "pairs_reconciliation.csv")
241
+ assert int(bc.has_sc.sum()) == len(rec)
242
+ assert set(rec.sample_id) == set(bc.sample_id[bc.has_sc.astype(bool)])
243
+ id_ok = rec.sex_all_four_agree.astype(bool) & rec.expr_identity_own_is_best.astype(bool)
244
+ comp_ok = rec.composition_eligible.astype(bool)
245
+ n_train = int((id_ok & comp_ok).sum())
246
+ n_nocomp = int((id_ok & ~comp_ok).sum())
247
+ n_excl = int((~id_ok).sum())
248
+ n_strict = int(rec.strict_identity_eligible.astype(bool).sum())
249
+ bo = bc[~bc.has_sc.astype(bool)]
250
+ pu = bc[bc.sample_id.isin(set(rec.sample_id[id_ok & comp_ok]))]
251
+ bo_grp, pu_grp = Counter(bo.group), Counter(pu.group)
252
+ add_groups("Arunachalam 2020 COVID", pu_grp, bo_grp, str(meta / "bulk_cohort.csv"))
253
+ paired_subj = set(bc.subject_norm[bc.has_sc.astype(bool)])
254
+ arun_flag = bo[~bo.expr_sex_matches_geo.astype(bool)]
255
+ # zero-shot (no LoRA) cells for all bulk-only samples already exist: base model, raw / TPM / cal inputs
256
+ rc = json.load(open(US / "arunachalam_4arm" / "receipts" / "receipt_checks.json"))
257
+ assert rc["all_ok"]
258
+ zs_bo = {k: v for k, v in rc["tags"].items() if v["block"].startswith("bulkonly")}
259
+ zs_bo_arms = sorted({v["arm"] for v in zs_bo.values()})
260
+ zs_bo_bulks = {a: sum(v["bulks"] for v in zs_bo.values() if v["arm"] == a) for a in zs_bo_arms}
261
+ assert set(zs_bo_bulks.values()) == {len(bo)}, zs_bo_bulks
262
+ zs_ckpt = rc["checkpoint"]["path"]
263
+ assert zs_ckpt.endswith("f01_6k_1x_seed20260627/checkpoint_epoch_016.pt")
264
+ dr = pd.read_csv(US / "arunachalam_4arm" / "global_r" / "decision_rule.csv")
265
+ dr_pre = dr[dr.preregistered.astype(bool)]
266
+ arun_best_pass = int(dr_pre["n_populations_exceeding_raw_broadcast_by_0.018"].max())
267
+ arun_npop = int(dr_pre.populations.iloc[0])
268
+ rows.append(dict(
269
+ cohort="Arunachalam 2020 COVID", specimen="PBMC bulk; DC-enriched sc",
270
+ bulk_total=len(bc), paired=len(rec), seg_train=n_train, seg_nocomp=n_nocomp, seg_excl=n_excl,
271
+ excl_why=json.dumps({"identity_fail": n_excl}), bulk_only=len(bo),
272
+ donors_bulk_total=bc.subject_norm.nunique(),
273
+ donors_paired_usable=pu.subject_norm.nunique(), donors_bulk_only=len(set(bc.subject_norm) - paired_subj),
274
+ donors_excl_only=0,
275
+ bulk_only_groups=f"{bo_grp.get('COVID', 0)} COVID, {bo_grp.get('HC', 0)} healthy, {bo_grp.get('CONV', 0)} conv.",
276
+ sex_flag_bulk_only=len(arun_flag), sex_flag_ids=";".join(arun_flag.sample_id),
277
+ lora_cv="none", lora_comp_l1=np.nan, comp_null=np.nan, lora_logfc_r=np.nan, zs_raw_logfc_r=np.nan,
278
+ extra=(f"paired identity pass {int(id_ok.sum())}/{len(rec)}, composition_eligible {int(comp_ok.sum())}/{len(rec)} "
279
+ f"(material {';'.join(sorted(set(rec.material_status)))}), strict_identity_eligible {n_strict}; "
280
+ f"zero-shot bulk-only generated: arms {','.join(zs_bo_arms)}, {len(bo)} bulks each ({zs_ckpt}); "
281
+ f"prereg decision rule: best arm beats broadcast in {arun_best_pass}/{arun_npop} populations"),
282
+ usable_rule="identity pass (sex_all_four_agree & expr_identity_own_is_best) AND composition_eligible",
283
+ source=f"{meta/'bulk_cohort.csv'}; {meta/'pairs_reconciliation.csv'}; "
284
+ f"{US/'arunachalam_4arm/receipts/receipt_checks.json'}; {US/'arunachalam_4arm/global_r/decision_rule.csv'}",
285
+ ))
286
+ q("Arunachalam paired, composition-eligible", int(comp_ok.sum()), f"{meta/'pairs_reconciliation.csv'} composition_eligible")
287
+ q("Arunachalam zero-shot bulk-only samples generated (per input arm)", len(bo),
288
+ f"{US/'arunachalam_4arm/receipts/receipt_checks.json'} tags *_bulkonly_a/b bulks")
289
+ q("Arunachalam prereg: populations where any zero-shot arm beats broadcast", f"{arun_best_pass}/{arun_npop}",
290
+ US / "arunachalam_4arm" / "global_r" / "decision_rule.csv")
291
+
292
+ # ---------------- not plotted: Asan vaccine (no donor map), Giroux 2022 (broadcast beats LoRA) ----------------
293
+ asan_bulk = pd.read_csv(US / "asan_cll" / "conditions" / "asan" / "samples.csv")
294
+ asan_sc = pd.read_csv(US / "asan_cll" / "observed" / "asan" / "libraries.csv")
295
+ asan_note = dict(bulk=len(asan_bulk), subjects=asan_bulk.subject.nunique(), sc_libraries=len(asan_sc),
296
+ reason="no bulk-sc donor map (asan_cll/RESULTS.md section 1)")
297
+ gd = PF / "giroux2022"
298
+ gpairs = pd.read_csv(gd / "pairs.csv")
299
+ gman = json.load(open(gd / "MANIFEST.json"))
300
+ g_bo = [x for x in gman["excluded"]["bulk_count_columns_without_pair"]
301
+ if x["unpaired_reason"] == "no_sc_library_for_this_subject_day"]
302
+ gh = json.load(open(SCORES / "giroux2022" / "pooled" / "summary.json"))["headline"]["real_lora__raw"]
303
+ g_r, g_rb = gh["contrast_mean_cp10k_r_gen"], gh["contrast_mean_cp10k_r_broadcast"]
304
+ g_deg, g_degb = gh["deg_top50_sum"], gh["deg_top50_sum_broadcast"]
305
+ assert g_rb > g_r and g_degb > g_deg, "Giroux: broadcast no longer beats LoRA"
306
+ giroux_note = dict(pairs_qc_pass=int(gpairs.identity_pass.astype(bool).sum()), bulk_only_author_columns=len(g_bo),
307
+ lora_r=g_r, broadcast_r=g_rb, lora_deg=g_deg, broadcast_deg=g_degb)
308
+ q("Giroux QC-pass pairs (not shown)", giroux_note["pairs_qc_pass"], gd / "pairs.csv")
309
+ q("Giroux author bulk columns without sc (not shown)", len(g_bo),
310
+ f"{gd/'MANIFEST.json'} excluded.bulk_count_columns_without_pair (no_sc_library_for_this_subject_day)")
311
+ q("Giroux pooled LoRA vs broadcast: severe-mild r / top-50 DEG sum",
312
+ f"{g_r:.2f} vs {g_rb:.2f} / {g_deg} vs {g_degb}", SCORES / "giroux2022" / "pooled" / "summary.json")
313
+ lora_rank = int(re.search(r"Rank (\d+), alpha", (PFT / "README.md").read_text()).group(1))
314
+ q("LoRA rank", lora_rank, PFT / "README.md")
315
+
316
+ tab = pd.DataFrame(rows)
317
+ assert (tab.seg_train + tab.seg_nocomp + tab.seg_excl == tab.paired).all()
318
+ assert (tab.paired + tab.bulk_only == tab.bulk_total).all()
319
+ assert (tab.donors_paired_usable + tab.donors_bulk_only + tab.donors_excl_only
320
+ + np.where(tab.seg_nocomp > 0, tab.donors_bulk_total - tab.donors_bulk_only, 0) == tab.donors_bulk_total).all()
321
+ tab["lora_cv_source"] = [str(SCORES / k / "AGGREGATE.md") if r.lora_cv != "none" else "no paired-FT dataset built"
322
+ for k, r in zip(["ye2026_sepsis", "imperial_eskd", "ji2025_chili", None], tab.itertuples())]
323
+ for r in tab.itertuples():
324
+ for item in ["bulk_total", "seg_train", "seg_nocomp", "seg_excl", "bulk_only", "donors_paired_usable",
325
+ "donors_bulk_only", "donors_excl_only", "donors_bulk_total", "sex_flag_bulk_only"]:
326
+ q(f"{r.cohort}: {item}", getattr(r, item), r.source)
327
+ if r.lora_cv != "none":
328
+ q(f"{r.cohort}: LoRA 5-fold comp L1 / LOO null", f"{r.lora_comp_l1:.2f} / {r.comp_null:.2f}", r.lora_cv_source)
329
+ tab.to_csv(DATA / "sec10_cohort_counts.csv", index=False)
330
+ pd.DataFrame(groups).to_csv(DATA / "sec10_bulk_only_groups.csv", index=False)
331
+ qt = pd.DataFrame(quoted)
332
+ qt.to_csv(DATA / "sec10_quoted_numbers.csv", index=False)
333
+ print(tab.drop(columns=["source"]).T.to_string())
334
+ print("Asan (not plotted):", asan_note)
335
+ print("Giroux (not plotted):", giroux_note)
336
+
337
+ # ---------------- figure ----------------
338
+ C_TRAIN = style.INK
339
+ C_BO, C_BO_EDGE = style.PBISC_PALE, style.ARM["pbisc"]
340
+ DASH = (0, (3, 2))
341
+ W = style.TALL[0]
342
+ ROW = 1.10 # inches per cohort block
343
+ BAR_Y, BAR_H = 0.40, 0.27 # bar centre offset from block top, bar height (inches)
344
+ TOP = 0.78 # inches above the first block for the PLANNED line and the legend
345
+ AX_BOTTOM = 0.48 # inches for the x axis under the last block
346
+ n = len(tab)
347
+ H = TOP + n * ROW + AX_BOTTOM
348
+ fig = plt.figure(figsize=(W, H))
349
+ ax = fig.add_axes([0.0, AX_BOTTOM / H, 1.0, (n * ROW) / H])
350
+ xmax = tab.bulk_total.max()
351
+ XR = xmax * 1.30 # room right of the longest bar for its total label
352
+ ax.set_xlim(0, XR)
353
+ ax.set_ylim(n * ROW, 0) # y in inches from the top of the first block
354
+ FS_MAIN, FS_SUB = 13, 11
355
+
356
+ inbar = [] # (text, patch, row index)
357
+ for i, r in enumerate(tab.itertuples()):
358
+ y0 = i * ROW
359
+ yb = y0 + BAR_Y
360
+ ax.text(0, y0, r.cohort, ha="left", va="top", fontsize=FS_MAIN, fontweight="bold", color=style.INK)
361
+ if r.lora_cv != "none":
362
+ status = f"LoRA 5-fold: comp L1 {r.lora_comp_l1:.2f} vs null {r.comp_null:.2f}"
363
+ else:
364
+ status = "no LoRA: DC-enriched sc, no composition truth" # no broadcast comparison (2026-10-08)
365
+ ax.text(XR, y0, status, ha="right", va="top", fontsize=FS_SUB, color=style.SUBINK)
366
+ x = 0
367
+ p_tr = ax.barh(yb, r.seg_train, left=x, height=BAR_H, color=C_TRAIN, edgecolor=C_TRAIN, linewidth=0.8)[0]
368
+ x += r.seg_train
369
+ p_nc = ax.barh(yb, r.seg_nocomp, left=x, height=BAR_H, facecolor="white", edgecolor=style.INK, hatch="////",
370
+ linewidth=0.8)[0]
371
+ x += r.seg_nocomp
372
+ ax.barh(yb, r.seg_excl, left=x, height=BAR_H, facecolor="white", edgecolor=style.GREY, hatch="xxx", linewidth=0.8)
373
+ x += r.seg_excl
374
+ p_bo = ax.barh(yb, r.bulk_only, left=x, height=BAR_H, color=C_BO, edgecolor=C_BO_EDGE, linewidth=1.0,
375
+ linestyle=DASH)[0]
376
+ if r.seg_train:
377
+ inbar.append((ax.text(r.seg_train / 2, yb, f"{r.seg_train}", ha="center", va="center", color="white",
378
+ fontsize=12, fontweight="bold"), p_tr, i))
379
+ if r.seg_nocomp:
380
+ inbar.append((ax.text(r.seg_train + r.seg_nocomp / 2, yb, f"{r.seg_nocomp}", ha="center", va="center",
381
+ color=style.INK, fontsize=12, fontweight="bold",
382
+ bbox=dict(facecolor="white", edgecolor="none", pad=0.6)), p_nc, i))
383
+ inbar.append((ax.text(r.paired + r.bulk_only / 2, yb, f"{r.bulk_only}", ha="center", va="center",
384
+ color=style.INK, fontsize=12, fontweight="bold"), p_bo, i))
385
+ excl = f" ({r.seg_excl} excl.)" if r.seg_excl else ""
386
+ ax.text(r.bulk_total + xmax * 0.015, yb, f"{r.bulk_total}{excl}", ha="left", va="center", color=style.INK,
387
+ fontsize=12, gid=f"total{i}")
388
+ flag = f"; {r.sex_flag_bulk_only} sex-flagged" if r.sex_flag_bulk_only else ""
389
+ if r.cohort.startswith("Ji"):
390
+ flag += f" ({len(ji_flag_bc)} ChILI pre-ICI)"
391
+ if r.cohort.startswith("Arunachalam"):
392
+ flag += "; zero-shot cells made"
393
+ line1 = f"{r.specimen} · bulk-only: {r.bulk_only_groups}{flag}"
394
+ if r.seg_nocomp:
395
+ line2 = (f"donors: {r.donors_bulk_total - r.donors_bulk_only} paired "
396
+ f"({r.seg_train}/{r.paired} composition-eligible), {r.donors_bulk_only} bulk-only")
397
+ else:
398
+ line2 = (f"donors: {r.donors_paired_usable} paired, {r.donors_bulk_only} bulk-only, "
399
+ f"{r.donors_excl_only} excluded")
400
+ if r.cohort.startswith("Ji"):
401
+ line2 += f"; {len(ji_bc_sc_unpaired)} pre-ICI ChILI sc, no bulk"
402
+ ax.text(0, yb + BAR_H / 2 + 0.07, line1, ha="left", va="top", fontsize=FS_SUB, color=style.SUBINK)
403
+ ax.text(0, yb + BAR_H / 2 + 0.27, line2, ha="left", va="top", fontsize=FS_SUB, color=style.SUBINK)
404
+
405
+ ax.set_yticks([])
406
+ ax.spines["left"].set_visible(False)
407
+ ax.set_xticks([0, 100, 200, 300])
408
+ ax.spines["bottom"].set_bounds(0, 300)
409
+ ax.set_xlabel("bulk samples", fontsize=12)
410
+ ax.xaxis.set_label_coords(150 / XR, -0.05) # centred under the drawn 0-300 spine
411
+
412
+ leg = [Patch(facecolor=C_TRAIN, edgecolor=C_TRAIN, label="paired, QC pass: LoRA training"),
413
+ Patch(facecolor="white", edgecolor=style.GREY, hatch="xxx", label="paired, excluded (fail / borderline / <200 cells)"),
414
+ Patch(facecolor="white", edgecolor=style.INK, hatch="////", label="paired, DC-enriched sc: no composition"),
415
+ Patch(facecolor=C_BO, edgecolor=C_BO_EDGE, linestyle=DASH, label="bulk only: LoRA cells to generate")]
416
+ fig.legend(handles=leg, loc="upper left", bbox_to_anchor=(0.0, 1 - 0.30 / H), ncol=2, fontsize=11,
417
+ handlelength=1.5, handleheight=1.0, columnspacing=1.0, labelspacing=0.35, borderaxespad=0.0, borderpad=0.0)
418
+ fig.text(1.0, 1.0, "PLANNED: no LoRA cells for bulk-only yet", ha="right", va="top", fontsize=13,
419
+ fontweight="bold", color=style.INK)
420
+
421
+ # in-bar numbers that do not fit their segment move to one "a + b = total" label right of the bar
422
+ fig.canvas.draw()
423
+ rend = fig.canvas.get_renderer()
424
+ misfit = {i for t, pch, i in inbar if t.get_window_extent(rend).width > pch.get_window_extent(rend).width - 6}
425
+ for i in misfit:
426
+ r = tab.iloc[i]
427
+ for t, pch, j in inbar:
428
+ if j == i:
429
+ t.remove()
430
+ tot = [t for t in ax.texts if t.get_gid() == f"total{i}"][0]
431
+ parts = [str(v) for v in (r.seg_train, r.seg_nocomp, r.seg_excl) if v] + [str(r.bulk_only)]
432
+ tot.set_text(" + ".join(parts) + f" = {r.bulk_total}")
433
+ print("rows with outside labels:", [tab.iloc[i].cohort for i in sorted(misfit)])
434
+
435
+ # guard: no two text boxes overlap, and every text stays inside the figure
436
+ fig.canvas.draw()
437
+ texts = [t for t in ax.texts + fig.texts if t.get_visible() and t.get_text()]
438
+ boxes = [(t.get_text()[:30], t.get_window_extent(rend)) for t in texts]
439
+ boxes.append(("legend", fig.legends[0].get_window_extent(rend)))
440
+ fb = fig.bbox
441
+ for k, (s1, b1) in enumerate(boxes):
442
+ assert b1.x0 >= fb.x0 - 1 and b1.x1 <= fb.x1 + 1 and b1.y0 >= fb.y0 - 1 and b1.y1 <= fb.y1 + 1, f"outside: {s1}"
443
+ for s2, b2 in boxes[k + 1:]:
444
+ assert not b1.overlaps(b2), f"text overlap: {s1!r} / {s2!r}"
445
+ print(f"figure {W:.2f} x {H:.2f} in; {len(boxes)} text boxes, no overlap")
446
+ style.save(fig, "sec10_paired_subset_cohorts", FIG)
447
+ print("saved", FIG / "sec10_paired_subset_cohorts.png")
448
+ print(qt.to_string())
paper-releases/pbisc-diffusion/updates/20261008T125804Z-deck-fig2-3-healthy-fig5-rare/diffusion/dataset/server_1/model8/presentations/2026-09-30--paper-summary--r00/tools/sync_sec09_text.py ADDED
@@ -0,0 +1,85 @@
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1
+ #!/usr/bin/env python3
2
+ """Copy generated slide text into data/slides_spec.json.
3
+
4
+ sec09_paired_validation.py regenerates titles, keywords and footnotes from the
5
+ scores (the scSemiProfiler verdicts can change when the missing draws arrive).
6
+ Run after that script and before generate_deck.py:
7
+
8
+ python3 tools/sec09_paired_validation.py
9
+ python3 tools/sync_sec09_text.py
10
+ python3 generate_deck.py
11
+
12
+ Two kinds of spec slides are synced:
13
+ - "sec09_index": i -> slide i of data/sec09_slide_text.json (section 9 main slides)
14
+ - "text_source": {"file": "data/<x>_slide_text.json", "index": i}
15
+ -> slide i of that file (added 2026-10-02: data/sec09_extra_slide_text.json from
16
+ tools/sec09_extra_metrics.py, data/sec07_rank_sweep_slide_text.json from
17
+ tools/sec07_rank_sweep.py)
18
+
19
+ Titles, keywords, footnote_full, numbers and (from footnote_short) the on-slide footnote
20
+ are overwritten; if footnote_full changed, the script lists the slide so the
21
+ short copy can be checked by hand (the deck build fails if it exceeds 2 lines).
22
+ """
23
+ import json
24
+ import sys
25
+ from pathlib import Path
26
+
27
+ DECK = Path(__file__).resolve().parents[1]
28
+ SPEC = Path(sys.argv[1]) if len(sys.argv) > 1 else DECK / "data" / "slides_spec.json"
29
+ SRC = DECK / "data" / "sec09_slide_text.json"
30
+ # section-9 slides deliberately left out of the deck (index -> why); every other index must be used exactly once
31
+ RETIRED = {2: "5 donors: LoRA vs scSemiProfiler — disease signal; superseded 2026-10-08 by tools/fig4_disease.py "
32
+ "(5-pair comparison without the bulk-broadcast baseline, partial r added)",
33
+ 3: "5-fold CV: train on the other 4 folds; superseded 2026-10-08 by tools/fig4_disease.py (5-fold disease, "
34
+ "no broadcast) and tools/fig23_healthy.py (ImMicro cells)"}
35
+
36
+
37
+ def copy_text(s: dict, g: dict, review: list) -> None:
38
+ figs = [str(Path(f).relative_to(DECK)) for f in g["figures"]]
39
+ have = [str(Path(f).relative_to(DECK)) if Path(f).is_absolute() else f for f in s["figures"]]
40
+ if figs != have:
41
+ raise SystemExit(f"figure mismatch for '{g['title']}': {figs} vs {s['figures']}")
42
+ s["figures"] = figs
43
+ s["title"] = g["title"]
44
+ s["keywords"] = g["keywords"]
45
+ if s.get("footnote_full", s.get("footnote")) != g["footnote"]:
46
+ review.append(g["title"])
47
+ s["footnote_full"] = g["footnote"]
48
+ if g.get("footnote_short"):
49
+ s["footnote"] = g["footnote_short"]
50
+ s["numbers"] = g["numbers"] # quoted numbers + sources, kept in step with the slide text (2026-10-01)
51
+
52
+
53
+ def main() -> None:
54
+ spec = json.loads(SPEC.read_text())
55
+ src = json.loads(SRC.read_text())["slides"]
56
+ review = []
57
+ n = 0
58
+ other: dict = {}
59
+ for s in spec["slides"]:
60
+ i = s.get("sec09_index")
61
+ if i is not None:
62
+ copy_text(s, src[i], review)
63
+ n += 1
64
+ continue
65
+ ts = s.get("text_source")
66
+ if ts:
67
+ f = DECK / ts["file"]
68
+ g = json.loads(f.read_text())["slides"]
69
+ copy_text(s, g[int(ts["index"])], review)
70
+ other.setdefault(ts["file"], set()).add(int(ts["index"]))
71
+ used = {s.get("sec09_index") for s in spec["slides"] if s.get("sec09_index") is not None}
72
+ if used & set(RETIRED) or n + len(RETIRED) != len(src) or any(src[i]["title"] != t.split(";")[0] for i, t in RETIRED.items()):
73
+ raise SystemExit(f"spec has {n} sec09 slides + {len(RETIRED)} retired, source has {len(src)}")
74
+ for f, idx in other.items():
75
+ m = len(json.loads((DECK / f).read_text())["slides"])
76
+ if idx != set(range(m)):
77
+ raise SystemExit(f"spec uses slides {sorted(idx)} of {f}, which has {m}")
78
+ SPEC.write_text(json.dumps(spec, indent=2, ensure_ascii=False) + "\n")
79
+ print(f"synced {n} section 9 slides and " + ", ".join(f"{len(v)} from {k}" for k, v in other.items()))
80
+ for t in review:
81
+ print(f"REVIEW short footnote (source footnote changed): {t}")
82
+
83
+
84
+ if __name__ == "__main__":
85
+ main()