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+ "keywords": [
56
+ "6,000 genes · 54.2M params · Bernoulli support draw"
57
+ ],
58
+ "footnote": "Fig. 1a redraw. Final model f01 6k 1x, epoch 16, EMA; 50 DDIM steps.",
59
+ "footnote_full": "Deck redraw of manuscript Fig. 1a (larger labels, legend dropped). Purple dashed = soft self-conditioning feedback; gold dashed = context to all blocks. Final model f01_6k_1x_seed20260627, checkpoint_epoch_016, EMA; 7 blocks 1024-1024-512-256-512-1024-1024 (effective_config.json, RUN_STATUS.json). Sampling: 50 DDIM steps, η = 0, drawn support read-out, keep gene if u < σ(logit) (methods.tex l.58, l.99). 16 epochs = 16 disjoint 8,192-recipe slots = one pass over the 131,072-recipe pool (manuscript: part 16).",
60
+ "sources": "tools/sec01_overview.py; data/sec01_model_numbers.csv, data/sec01_fig1_label_pt.csv"
61
+ },
62
+ {
63
+ "kind": "content",
64
+ "section": "2",
65
+ "section_label": "2 Backbone",
66
+ "title": "Backbone: SDD → PBISC-Diffusion",
67
+ "layout": "diagram",
68
+ "figures": [
69
+ "figures/sec02_backbone_compare.png"
70
+ ],
71
+ "keywords": [
72
+ "Kept from SDD: value + bit, skip-MLP",
73
+ "Changed: bulk condition, masked loss, Bernoulli read-out"
74
+ ],
75
+ "footnote": "SDD: Ostheimer et al., arXiv 2502.02448. scDiffusion: Luo et al., Bioinformatics 2024.",
76
+ "sources": "tools/sec02_backbone.py; data/sec02_backbone_compare.csv, data/sec02_slide_text.csv, data/refs/",
77
+ "footnote_full": "Luo et al., Bioinformatics 2024; Ostheimer et al., arXiv 2502.02448 (code 1d5423c). PBISC: final model f01 6k 1x, part 16. σ = sigmoid; Bernoulli is the final read-out; the logit > 0 cut is also reported."
78
+ },
79
+ {
80
+ "kind": "content",
81
+ "section": "2",
82
+ "section_label": "2 Backbone",
83
+ "title": "Bulk conditioning",
84
+ "layout": "diagram",
85
+ "figures": [
86
+ "figures/sec02_bulk_conditioning.png"
87
+ ],
88
+ "keywords": [
89
+ "Same bulk condition for every generated cell",
90
+ "Final: no cell types, proportions, sum constraint",
91
+ "18,006 → 512 context into every block"
92
+ ],
93
+ "footnote": "Final model f01 6k 1x. Bar heights schematic.",
94
+ "sources": "tools/sec02_backbone.py; data/sec02_bulk_conditioning.csv, data/sec02_slide_text.csv",
95
+ "footnote_full": "Final model f01 6k 1x, part 16. Bar heights schematic."
96
+ },
97
+ {
98
+ "kind": "content",
99
+ "section": "3",
100
+ "section_label": "3 Architecture ablation",
101
+ "title": "Width & context ablation: loss saturation",
102
+ "layout": "full",
103
+ "figures": [
104
+ "figures/sec03_width_loss.png"
105
+ ],
106
+ "keywords": [
107
+ "Trunk x4: val loss −31% (0.197 → 0.136)",
108
+ "ctx x4, prop hint: loss = 1x",
109
+ "1x flat E8; trunk x4 still falling"
110
+ ],
111
+ "footnote": "Old 6k panel (1% floor); one validation set. 16x: memory-floor stop after part 2.",
112
+ "say": "All arms share the 6k panel (1% floor), corpus, seed and schedule; validation = 192 recipes x 64 cells. ctx x4, both x4 and 16x were read from server_2 snapshots.",
113
+ "sources": "tools/sec03_width_loss.py; data/sec03_width_loss.csv, data/sec03_width_saturation.csv, data/sec03_width_loss_headline.csv"
114
+ },
115
+ {
116
+ "kind": "content",
117
+ "section": "3",
118
+ "section_label": "3 Architecture ablation",
119
+ "title": "Width & context ablation: benchmark",
120
+ "layout": "full",
121
+ "figures": [
122
+ "figures/sec03_width_bench.png"
123
+ ],
124
+ "keywords": [
125
+ "trunk x4: loss −31%, no DEG gain",
126
+ "Prop hint: oracle = predicted, L1 worse",
127
+ "1x kept: ties ctx x4, 54M vs 102M"
128
+ ],
129
+ "footnote": "SLE, 42 donors, 2,980 genes; old 6k panel. ctx x4: better L1 (0.161 vs 0.197).",
130
+ "say": "Bars = mean of parts 14-16 with the cut p > 0.5; diamonds = Bernoulli read-out (4 width arms only). Prop hint = 9 L1 cell-type proportions; older panel, not the final model.",
131
+ "sources": "tools/sec03_width_bench.py; data/sec03_width_bench.csv, data/sec03_width_bench_summary.csv, data/sec03_width_bench_headline.csv"
132
+ },
133
+ {
134
+ "kind": "content",
135
+ "section": "3",
136
+ "section_label": "3 Architecture ablation",
137
+ "title": "Gene context: 2k / 3k / 6k / 15k",
138
+ "layout": "full",
139
+ "figures": [
140
+ "figures/sec03_panel.png"
141
+ ],
142
+ "keywords": [
143
+ "6k ≈ 3k: 3k inside 6k seed range",
144
+ "2k best L1; 15k worst r, L1",
145
+ "6k kept: first panel with CLEC9A (cDC1)"
146
+ ],
147
+ "footnote": "SLE, 42 donors, 1,006 benchmark genes in every panel; 6k base seed = best of 5.",
148
+ "say": "Runs f01_{2k,3k,6k,p15k}_1x, part 16, Bernoulli, EMA, DDIM 50. Different gene axis from the previous slide, so the two slides cannot be compared. Loss curves are divided by each panel's own part-16 value.",
149
+ "sources": "tools/sec03_panel.py; data/sec03_panel_bench.csv, data/sec03_panel_seeds.csv, data/sec03_panel_loss.csv, data/sec03_panel_headline.csv"
150
+ },
151
+ {
152
+ "kind": "content",
153
+ "section": "4",
154
+ "section_label": "4 SLE benchmark",
155
+ "title": "SLE benchmark: PBISC vs scSemiProfiler",
156
+ "layout": "full",
157
+ "figures": [
158
+ "figures/sec04_sle_benchmark.png"
159
+ ],
160
+ "keywords": [
161
+ "42 held-out donors, sc-pseudobulk input",
162
+ "Beats scSemiProfiler on all three metrics",
163
+ "Ties PBISC-VAE; below bulk-copy baseline"
164
+ ],
165
+ "footnote": "GSE135779, 42 held-out donors (30 SLE / 12 HC). PBISC: 5 seeds, mean ± SD; baselines: 1 draw.",
166
+ "sources": "tools/sec04_sle_benchmark.py; data/sec04_sle_benchmark.csv, data/sec04_sle_numbers.csv",
167
+ "footnote_full": "GSE135779, 42 held-out donors (30 SLE / 12 HC). PBISC f01 6k E16, 5 seeds (mean ± SD); baselines 1 draw. scSemiProfiler also gets real sc of 14 in-cohort donors (1,500 cells each). Dashed: input bulk logFC copied to every type (backup)."
168
+ },
169
+ {
170
+ "kind": "content",
171
+ "section": "4",
172
+ "section_label": "4 SLE benchmark",
173
+ "title": "SLE benchmark: per cell type",
174
+ "layout": "full",
175
+ "figures": [
176
+ "figures/sec04_sle_per_celltype.png"
177
+ ],
178
+ "keywords": [
179
+ "Beats scSemiProfiler in T, B, Mono, NK",
180
+ "Loses in rare DC and Other",
181
+ "DC: ~15 generated cells per donor"
182
+ ],
183
+ "footnote": "Same 42 donors, 1,006 genes. PBISC: 5 seeds, mean ± SD; baselines: 1 draw.",
184
+ "say": "PBISC's DC top list in the base seed has only 13 genes, because few DC cells are generated.",
185
+ "sources": "tools/sec04_sle_benchmark.py; data/sec04_sle_per_celltype.csv, data/sec04_sle_numbers.csv",
186
+ "footnote_full": "Same 42 donors, 1,006 genes. PBISC 5 seeds (mean ± SD), baselines 1 draw. Tick %: share of 251,179 real cells. Other top-50 is out of 12 truth genes. Bulk copy: r 0.68, top-50 113 (backup)."
187
+ },
188
+ {
189
+ "kind": "content",
190
+ "section": "5",
191
+ "section_label": "5 Real bulk vs pseudobulk",
192
+ "title": "Real bulk ≠ pseudobulk (model input)",
193
+ "layout": "figure_keywords",
194
+ "figures": [
195
+ "figures/sec05_condition_space.png"
196
+ ],
197
+ "keywords": [
198
+ "Real bulk: 2.46 D from own pseudobulk",
199
+ "95% of squared offset is one shift",
200
+ "Shift removed (diagnostic): own donor 7.5% → 75.7%"
201
+ ],
202
+ "footnote": "ImMicro, 107 healthy donors. Model input space (log1p CPM). D = median donor-to-donor distance.",
203
+ "say": "The two pseudobulk clusters on PC1 are sc pools DB1-3 vs DB4-7, so the pairing lines cross mainly because of sc batch. Shift removal subtracts the mean offset of the other 106 donors; a bulk-only deployment would not have them.",
204
+ "sources": "tools/sec05_condition_space.py; data/sec05_condition_space_numbers.csv, data/sec05_condition_space_coords.csv",
205
+ "footnote_full": "ImMicro, 107 healthy donors. Model inputs (log1p CPM, 5,508 genes), not learned ctx. D = median donor-to-donor distance; PCA-30 values are lower bounds (full space 3.19 D, 0.91 shared). Shift removal is a diagnostic that uses paired pseudobulks. Pseudobulk PC1 is sc pool batch (pool R² 0.96 on PC1)."
206
+ },
207
+ {
208
+ "kind": "content",
209
+ "section": "5",
210
+ "section_label": "5 Real bulk vs pseudobulk",
211
+ "title": "Consequence: cells off-manifold",
212
+ "layout": "two_figures",
213
+ "figures": [
214
+ "figures/sec05_cells_umap.png",
215
+ "figures/sec05_cells_metrics.png"
216
+ ],
217
+ "keywords": [
218
+ "Monocytes: raw 30.6% vs real 16.7%",
219
+ "Same noise: 19% T → monocyte",
220
+ "Precision/coverage: raw 0.36/0.08, pseudobulk 0.92/0.51"
221
+ ],
222
+ "footnote": "ImMicro, 107 donors; same starting noise for every input. refcal = cohort-mean bulk anchored to a healthy reference.",
223
+ "footnote_full": "ImMicro, 107 donors. Final model f01 6k 1× E16 (DDIM 50, EMA); each cell starts from the same noise under every input. Precision/coverage come from one scoring call. Composition L1: raw 0.455, pseudobulk 0.166, cohort-mean null 0.161. The UMAP is fitted on real cells and overstates overlap. refcal definition: plans/utility_studies_final6k_20260925/refcal/RESULTS.md ('Reference-anchored calibration ... anchoring a cohort's mean bulk to the AIFI healthy-PBMC reference'); AIDA reference: refcal_refs/RESULTS.md.",
224
+ "say": "TPM fixes cell shape (precision 0.87) but not monocytes (34.3%). refcal fixes monocytes (about 17.5%); coverage depends on the reference (AIFI 0.08, AIDA 0.37).",
225
+ "sources": "tools/sec05_cells_offmanifold.py; data/sec05_cells_metrics.csv, data/sec05_cells_umap_coords.csv"
226
+ },
227
+ {
228
+ "kind": "content",
229
+ "section": "5",
230
+ "section_label": "5 Real bulk vs pseudobulk",
231
+ "title": "Consequence: disease direction flips",
232
+ "layout": "figure_keywords",
233
+ "figures": [
234
+ "figures/sec05_behcet_direction.png"
235
+ ],
236
+ "keywords": [
237
+ "CD16 gap: raw −3.97 vs observed +4.94",
238
+ "C1Q flip vanishes at common depth",
239
+ "AIFI refcal restores sign, 5/5 seeds"
240
+ ],
241
+ "footnote": "Behçet. Bulk GSE198533 (9 BD / 10 HC); observed sc GSE198616 (4 / 4, different people).",
242
+ "say": "Limitations: AIDA refcal does not restore the sign (C1Q -0.25, CD16 +0.37). Best reference differs by cohort (AIDA for ImMicro, AIFI for Behcet). The sc pseudobulk ceiling uses the 8 sc donors, not the 19 bulk donors. Monocytes stay about 2x observed even under refcal.",
243
+ "sources": "tools/sec05_behcet_direction.py; data/sec05_behcet_direction.csv",
244
+ "footnote_full": "Behçet, final model. Bulk GSE198533 (BD 9, HC 10), 5,000 cells per sample; observed = sc GSE198616 (BD 4, HC 4, different people; descriptive p). At common depth, raw CD16 is −3.59 (seed 0) and raw C1Q is −0.08 ± 0.09 pp. AIDA refcal does not restore the sign."
245
+ },
246
+ {
247
+ "kind": "content",
248
+ "section": "5",
249
+ "section_label": "5 Real bulk vs pseudobulk",
250
+ "title": "Real bulk + refcal vs scSemiProfiler (ImMicro)",
251
+ "layout": "full",
252
+ "figures": [
253
+ "figures/sec04_immicro_external.png"
254
+ ],
255
+ "keywords": [
256
+ "Real bulk + refcal; no target sc",
257
+ "Lower L1, IFN error; rank not better",
258
+ "No-bulk replay: lower T error, rank ~0"
259
+ ],
260
+ "footnote": "ImMicro, 107 donors, 1 seed; CI = paired donor bootstrap.",
261
+ "say": "Section 4 author's slide ('External reference setting'), moved here after refcal is introduced. scSemiProfiler IFN variance ratio 0.036 (Mono) and 0.027 (T), vs PBISC 0.830 and 1.538.",
262
+ "sources": "tools/sec04_immicro.py; data/sec04_immicro_external.csv, data/sec04_immicro_numbers.csv",
263
+ "footnote_full": "ImMicro baseline, 107 donors, 1 generation seed, 5,500 genes; CI = paired donor bootstrap. Refcal is fit on the mean of all 107 bulks (transductive). PBISC pretraining includes part of AIFI and is not counted in generation time."
264
+ },
265
+ {
266
+ "kind": "content",
267
+ "section": "6",
268
+ "section_label": "6 Paired fine-tuning",
269
+ "title": "Fine-tuning with paired bulk + sc",
270
+ "layout": "diagram",
271
+ "figures": [
272
+ "figures/sec06_ft_method.png"
273
+ ],
274
+ "keywords": [
275
+ "LoRA 2–14 min vs pretraining 15.9 h"
276
+ ],
277
+ "footnote": "Base: final model f01 6k 1x E16. Times from 40 LoRA runs on this host.",
278
+ "sources": "tools/sec06_finetune_method.py; data/sec06_ft_method.csv",
279
+ "footnote_full": "Receipts: immicro/fold0/real_lora and ye2026_sepsis/fewshot_n5/draw0/lora RUN.json. Base: f01_6k_1x E16. Times: 40 local LoRA runs."
280
+ },
281
+ {
282
+ "kind": "content",
283
+ "section": "7",
284
+ "section_label": "7 LoRA ablations",
285
+ "title": "Full vs LoRA vs cond.-encoder-only",
286
+ "layout": "full",
287
+ "figures": [
288
+ "figures/sec07_ft_modes.png"
289
+ ],
290
+ "keywords": [
291
+ "LoRA ≈ full FT accuracy (n.s.)",
292
+ "42× fewer trainable params (1.3 M)",
293
+ "Cond.-encoder-only: no gain over zero-shot cal"
294
+ ],
295
+ "footnote": "Full vs LoRA: paired Wilcoxon on donor L1, p 0.25 / 0.71.",
296
+ "sources": "tools/sec07_ft_modes.py; data/sec07_ft_modes_accuracy.csv, data/sec07_ft_modes_compute.csv, data/sec07_ft_modes_wilcoxon.csv",
297
+ "footnote_full": "Base f01_6k_1x E16. Full vs LoRA: paired Wilcoxon, donor L1, p 0.25 / 0.71. Open = fold-0 pilot; compare same marker only. Per-step time: runs early-stop differently."
298
+ },
299
+ {
300
+ "kind": "content",
301
+ "section": "7",
302
+ "section_label": "7 LoRA ablations",
303
+ "title": "K diversification: no gain",
304
+ "layout": "figure_keywords",
305
+ "figures": [
306
+ "figures/sec07_k_aug.png"
307
+ ],
308
+ "keywords": [
309
+ "No gain; keep single K 1000",
310
+ "Multi-K slightly worse on ImMicro (p 0.04)",
311
+ "Inner-val loss Δ ≤ 1.2e-4"
312
+ ],
313
+ "footnote": "LoRA r16, 5-fold pooled. p = paired Wilcoxon on donor L1, uncorrected.",
314
+ "sources": "tools/sec07_k_aug.py; data/sec07_k_aug.csv, data/sec07_k_aug_wilcoxon.csv, data/sec07_k_aug_inner_val_delta.csv",
315
+ "footnote_full": "LoRA r16 on f01_6k_1x E16, 5-fold pooled. p: paired Wilcoxon, donor L1 vs plain LoRA, uncorrected. Recipes arm: K 1000 real bulk + ½-batch pretraining pseudobulk, no multi-K."
316
+ },
317
+ {
318
+ "kind": "content",
319
+ "section": "8",
320
+ "section_label": "8 Pairs needed",
321
+ "title": "Pairs needed: composition, coverage, training steps",
322
+ "layout": "full",
323
+ "figures": [
324
+ "figures/sec08_pairs_realism.png"
325
+ ],
326
+ "keywords": [
327
+ "Coverage, 5+7 pairs: ImMicro 0.84, sepsis 0.77"
328
+ ],
329
+ "footnote": "Donor 5-fold CV (ImMicro 107, sepsis 82 donors). N+7 = N training + 7 early-stop pairs.",
330
+ "footnote_full": "Final f01 6k·1× epoch-16 + LoRA; donor 5-fold CV, pooled scANVI scoring (ImMicro 107, sepsis 82 donors). N+7 = N training + 7 (sepsis 7–8) inner-val pairs for early stopping. cal = zero-shot + calibration, α fit on all 85–86 / 65–66 fold pairs; with α from the same 5 pairs (Sec. 9 call), coverage 0.54 vs LoRA 0.79 (ImMicro), 0.43 vs 0.69 (sepsis). Sec. 9 5-pair runs: fixed 3k steps, no inner-val. 20k cap reached by ImMicro folds 1/5 (10), 4/5 (20), 5/5 (40, all): val loss still falling, but last 2k steps <0.4% of total drop.",
331
+ "say": "Keywords say +7; 2 of 5 sepsis folds use 8 inner-val pairs.",
332
+ "sources": "tools/sec08_pairs_needed.py; data/sec08_pairs_realism.csv, data/sec08_selected_steps.csv, data/sec08_slide_numbers.csv"
333
+ },
334
+ {
335
+ "kind": "content",
336
+ "section": "8",
337
+ "section_label": "8 Pairs needed",
338
+ "title": "Pairs needed: donor and disease signal",
339
+ "layout": "figure_keywords",
340
+ "figures": [
341
+ "figures/sec08_pairs_signal.png"
342
+ ],
343
+ "keywords": [
344
+ "logFC r above broadcast from 10+7 pairs",
345
+ "DEG matches broadcast at 40+7 pairs",
346
+ "NK r 0.70 at 40+7 (cal 0.50)"
347
+ ],
348
+ "footnote": "Sepsis: 61 case vs 21 control. logFC r = mean over T / B / Mono / NK.",
349
+ "footnote_full": "Same runs and pooled scoring as previous slide; sepsis 61 case vs 21 control. N+7 = N training + 7 (sepsis 7–8) inner-val pairs. logFC r = mean over T/B/Mono/NK (mean CP10K); DEG = Welch top-50 overlap summed over T/B/Mono/NK/DC. ≤10 pairs: NK r (0.20/0.40) and DEG (5/8) below cal (0.50, 11); T r below cal until 40 pairs, Mono until all. DEG gain is Mono/DC; T overlap 5 (cal) → 0–1 from 20 pairs, NK 0 at every n (broadcast T 3, NK 2).",
350
+ "sources": "tools/sec08_pairs_needed.py; data/sec08_pairs_signal.csv, data/sec08_slide_numbers.csv"
351
+ },
352
+ {
353
+ "kind": "content",
354
+ "section": "9",
355
+ "section_label": "9 Paired validation",
356
+ "sec09_index": 0,
357
+ "title": "Five paired cohorts",
358
+ "layout": "full",
359
+ "figures": [
360
+ "figures/sec09_cohorts.png"
361
+ ],
362
+ "keywords": [
363
+ "403 paired samples, 275 donors",
364
+ "Only identity-pass pairs; donor-level splits",
365
+ "Ji bulk: whole blood, not PBMC"
366
+ ],
367
+ "footnote": "Usable pair = passed identity check and ≥ 200 cells: 403 of 430 pairs.",
368
+ "footnote_full": "Usable pair = passed the pairing identity check and >= 200 cells (fold >= 0 in data/<cohort>/folds.csv); dropped 15 identity-fail, 11 borderline and 1 low-cell pairs of 430. ImMicro: no identity flag, all used. Imperial, Giroux, Ji: several pairs per donor. Case vs control = samples in scores/<cohort>/pooled/summary.json. Giroux 'moderate' = GEO 'severe' (paper term). Labels: data/<cohort>/QC_REPORT.md; ImMicro: GEO GSE314922/GSE314416.",
369
+ "sources": "tools/sec09_paired_validation.py; data/sec09_cohorts.csv, data/sec09_quoted_numbers.csv, data/sec09_slide_text.json",
370
+ "numbers": [
371
+ {
372
+ "value": "403 paired samples (sum of usable rows)",
373
+ "source": "/home/sj_server_1/PBISC/immun-pbmc-fm/model_8_sparse_data_diffusion/plans/paired_finetune_intradataset_20260927/data/<cohort>/fewshot_n5/DRAWS.json (n_usable_rows)"
374
+ },
375
+ {
376
+ "value": "275 donors (sum of usable donors)",
377
+ "source": "/home/sj_server_1/PBISC/immun-pbmc-fm/model_8_sparse_data_diffusion/plans/paired_finetune_intradataset_20260927/data/<cohort>/fewshot_n5/DRAWS.json (n_usable_donors)"
378
+ },
379
+ {
380
+ "value": "dropped 15 identity-fail, 11 borderline, 1 < 200 cells, of 430",
381
+ "source": "/home/sj_server_1/PBISC/immun-pbmc-fm/model_8_sparse_data_diffusion/plans/paired_finetune_intradataset_20260927/data/<cohort>/features.npz (identity_pass, identity_check); samples.csv (n_cells); /home/sj_server_1/PBISC/immun-pbmc-fm/model_8_sparse_data_diffusion/plans/paired_finetune_intradataset_20260927/tools/prepare_dataset.py (MIN_CELLS)"
382
+ },
383
+ {
384
+ "value": "ImMicro 107 pairs / 107 donors",
385
+ "source": "/home/sj_server_1/PBISC/immun-pbmc-fm/model_8_sparse_data_diffusion/plans/paired_finetune_intradataset_20260927/data/immicro/fewshot_n5/DRAWS.json"
386
+ },
387
+ {
388
+ "value": "Sepsis 82 pairs / 82 donors; sepsis 61 vs control 21",
389
+ "source": "/home/sj_server_1/PBISC/immun-pbmc-fm/model_8_sparse_data_diffusion/plans/paired_finetune_intradataset_20260927/data/ye2026_sepsis/fewshot_n5/DRAWS.json; /home/sj_server_1/PBISC/immun-pbmc-fm/model_8_sparse_data_diffusion/plans/paired_finetune_intradataset_20260927/scores/ye2026_sepsis/pooled/summary.json"
390
+ },
391
+ {
392
+ "value": "Imperial 157 pairs / 57 donors; COVID+ 113 vs COVID− 34 (+10 recovery, neither)",
393
+ "source": "/home/sj_server_1/PBISC/immun-pbmc-fm/model_8_sparse_data_diffusion/plans/paired_finetune_intradataset_20260927/data/imperial_eskd/fewshot_n5/DRAWS.json; /home/sj_server_1/PBISC/immun-pbmc-fm/model_8_sparse_data_diffusion/plans/paired_finetune_intradataset_20260927/scores/imperial_eskd/pooled/summary.json"
394
+ },
395
+ {
396
+ "value": "Giroux 24 pairs / 9 donors; moderate 11 vs mild 13",
397
+ "source": "/home/sj_server_1/PBISC/immun-pbmc-fm/model_8_sparse_data_diffusion/plans/paired_finetune_intradataset_20260927/data/giroux2022/fewshot_n5/DRAWS.json; /home/sj_server_1/PBISC/immun-pbmc-fm/model_8_sparse_data_diffusion/plans/paired_finetune_intradataset_20260927/scores/giroux2022/pooled/summary.json"
398
+ },
399
+ {
400
+ "value": "Ji 33 pairs / 20 donors; ChILI 18 vs ICI control 15",
401
+ "source": "/home/sj_server_1/PBISC/immun-pbmc-fm/model_8_sparse_data_diffusion/plans/paired_finetune_intradataset_20260927/data/ji2025_chili/fewshot_n5/DRAWS.json; /home/sj_server_1/PBISC/immun-pbmc-fm/model_8_sparse_data_diffusion/plans/paired_finetune_intradataset_20260927/scores/ji2025_chili/pooled/summary.json"
402
+ }
403
+ ]
404
+ },
405
+ {
406
+ "kind": "content",
407
+ "section": "9",
408
+ "section_label": "9 Paired validation",
409
+ "sec09_index": 1,
410
+ "title": "5 donors: LoRA vs scSemiProfiler — cells",
411
+ "layout": "full",
412
+ "figures": [
413
+ "figures/sec09_fewpair_cells.png"
414
+ ],
415
+ "keywords": [
416
+ "LoRA-5 > scSemi-5: coverage, precision 5/5; L1 4/5",
417
+ "Coverage: LoRA-5 0.69–0.96 vs scSemi-5 0.04–0.61",
418
+ "Composition gain vs zero-shot: ImMicro only"
419
+ ],
420
+ "footnote": "5 draws per cohort; test = all other usable pairs. scANVI labels; P/C = PCA-50, k = 10.",
421
+ "footnote_full": "Base f01 6k·1x·E16 (EMA, DDIM 50) + LoRA r=16, 3,000 steps. LoRA-5 / scSemi-5 = LoRA / scSemiProfiler trained on the same 5 donors (5–15 pairs); test = all other usable pairs. scSemi-5 scored in a separate call, same test set and reference (sha-checked); 25/25 draws (missing: none). Verdict = better in >= 80% of shared draws (L1: Giroux split 3/5). Depth-matched P/C: same ranking, coverage LoRA-5 0.83–0.97 vs scSemi-5 0.15–0.28. L1 vs zero-shot: per-donor Wilcoxon, ImMicro p 2e-10; others p >= 0.38. scANVI labels; P/C = PCA-50, k=10 balls. Scores: scores/<cohort>/fewshot_n5/.",
422
+ "say": "scSemi-5 is missing draw4 for ImMicro and Sepsis. When those arrive, rerun tools/sec09_paired_validation.py, then tools/sync_sec09_text.py, then generate_deck.py.",
423
+ "sources": "tools/sec09_paired_validation.py; data/sec09_fewpair_cells.csv, data/sec09_scsemi_status.csv, data/sec09_slide_text.json",
424
+ "numbers": [
425
+ {
426
+ "value": "LoRA-5 vs scSemi-5 coverage (shared-draw means; LoRA-better draws/n; verdict): ImMicro 0.792 vs 0.036 (5/5, lora); Sepsis 0.694 vs 0.080 (5/5, lora); Imperial 0.737 vs 0.059 (5/5, lora); Giroux 0.961 vs 0.607 (5/5, lora); Ji 0.707 vs 0.145 (5/5, lora) -> LoRA verdicts 5/5",
427
+ "source": "/home/sj_server_1/PBISC/immun-pbmc-fm/model_8_sparse_data_diffusion/plans/paired_finetune_intradataset_20260927/scores/<cohort>/fewshot_n5/draw<j>/summary.json and draw<j>_scsemi5/summary.json"
428
+ },
429
+ {
430
+ "value": "LoRA-5 vs scSemi-5 precision (shared-draw means; LoRA-better draws/n; verdict): ImMicro 0.952 vs 0.518 (5/5, lora); Sepsis 0.906 vs 0.728 (5/5, lora); Imperial 0.853 vs 0.330 (5/5, lora); Giroux 1.000 vs 0.992 (5/5, lora); Ji 0.978 vs 0.840 (5/5, lora) -> LoRA verdicts 5/5",
431
+ "source": "/home/sj_server_1/PBISC/immun-pbmc-fm/model_8_sparse_data_diffusion/plans/paired_finetune_intradataset_20260927/scores/<cohort>/fewshot_n5/draw<j>/summary.json and draw<j>_scsemi5/summary.json"
432
+ },
433
+ {
434
+ "value": "LoRA-5 vs scSemi-5 comp_l1 (shared-draw means; LoRA-better draws/n; verdict): ImMicro 0.176 vs 0.233 (5/5, lora); Sepsis 0.466 vs 0.612 (5/5, lora); Imperial 0.503 vs 0.602 (5/5, lora); Giroux 0.256 vs 0.270 (3/5, split); Ji 0.513 vs 0.592 (4/5, lora) -> LoRA verdicts 4/5",
435
+ "source": "/home/sj_server_1/PBISC/immun-pbmc-fm/model_8_sparse_data_diffusion/plans/paired_finetune_intradataset_20260927/scores/<cohort>/fewshot_n5/draw<j>/summary.json and draw<j>_scsemi5/summary.json"
436
+ },
437
+ {
438
+ "value": "LoRA-5 vs scSemi-5 coverage_dm (shared-draw means; LoRA-better draws/n; verdict): ImMicro 0.966 vs 0.284 (5/5, lora); Sepsis 0.834 vs 0.158 (5/5, lora); Imperial 0.863 vs 0.152 (5/5, lora); Giroux 0.974 vs 0.238 (5/5, lora); Ji 0.908 vs 0.150 (5/5, lora) -> LoRA verdicts 5/5",
439
+ "source": "/home/sj_server_1/PBISC/immun-pbmc-fm/model_8_sparse_data_diffusion/plans/paired_finetune_intradataset_20260927/scores/<cohort>/fewshot_n5/draw<j>/summary.json and draw<j>_scsemi5/summary.json"
440
+ },
441
+ {
442
+ "value": "LoRA-5 vs scSemi-5 precision_dm (shared-draw means; LoRA-better draws/n; verdict): ImMicro 0.975 vs 0.829 (5/5, lora); Sepsis 0.914 vs 0.504 (5/5, lora); Imperial 0.881 vs 0.429 (5/5, lora); Giroux 0.995 vs 0.426 (5/5, lora); Ji 0.974 vs 0.564 (5/5, lora) -> LoRA verdicts 5/5",
443
+ "source": "/home/sj_server_1/PBISC/immun-pbmc-fm/model_8_sparse_data_diffusion/plans/paired_finetune_intradataset_20260927/scores/<cohort>/fewshot_n5/draw<j>/summary.json and draw<j>_scsemi5/summary.json"
444
+ },
445
+ {
446
+ "value": "coverage cohort means over all draws: LoRA-5 ImMicro 0.792, Sepsis 0.694, Imperial 0.737, Giroux 0.961, Ji 0.707; scSemi-5 ImMicro 0.036, Sepsis 0.080, Imperial 0.059, Giroux 0.607, Ji 0.145",
447
+ "source": "/home/sj_server_1/PBISC/immun-pbmc-fm/model_8_sparse_data_diffusion/plans/paired_finetune_intradataset_20260927/scores/<cohort>/fewshot_n5/draw<j>/summary.json and draw<j>_scsemi5/summary.json"
448
+ },
449
+ {
450
+ "value": "LoRA-5 minus zero-shot-cal composition L1, per-donor Wilcoxon (draw-averaged): ImMicro -0.027, n=107, p=2.2e-10; Sepsis +0.018, n=82, p=0.79; Imperial +0.016, n=57, p=0.38; Giroux -0.065, n=8, p=0.38; Ji -0.012, n=20, p=0.7",
451
+ "source": "/home/sj_server_1/PBISC/immun-pbmc-fm/model_8_sparse_data_diffusion/plans/paired_finetune_intradataset_20260927/scores/<cohort>/fewshot_n5/draw<j>/per_donor.csv; /home/sj_server_1/PBISC/immun-pbmc-fm/model_8_sparse_data_diffusion/plans/paired_finetune_intradataset_20260927/data/<cohort>/folds.csv"
452
+ },
453
+ {
454
+ "value": "scSemiProfiler draws used / LoRA draws: ImMicro 5/5, Sepsis 5/5, Imperial 5/5, Giroux 5/5, Ji 5/5",
455
+ "source": "/home/sj_server_1/PBISC/immun-pbmc-fm/model_8_sparse_data_diffusion/presentations/2026-09-30--paper-summary--r00/data/sec09_scsemi_status.csv"
456
+ },
457
+ {
458
+ "value": "training pairs per draw: ImMicro 5, Sepsis 5, Imperial 12–15, Giroux 12–14, Ji 7–9; test pairs: ImMicro 102, Sepsis 77, Imperial 142–145, Giroux 10–12, Ji 24–26",
459
+ "source": "/home/sj_server_1/PBISC/immun-pbmc-fm/model_8_sparse_data_diffusion/plans/paired_finetune_intradataset_20260927/data/<cohort>/fewshot_n5/DRAWS.json (n_train_rows, n_test_rows)"
460
+ },
461
+ {
462
+ "value": "LoRA r = 16; 3000 fixed steps; base runs/f01_6k_1x_seed20260627/checkpoint_epoch_016.pt; sampling: test donors only, 1,500 cells each, seed 20260927, DDIM 50, EMA, Bernoulli read-out",
463
+ "source": "/home/sj_server_1/PBISC/immun-pbmc-fm/model_8_sparse_data_diffusion/plans/paired_finetune_intradataset_20260927/runs/immicro/fewshot_n5/draw0/lora/RUN.json; /home/sj_server_1/PBISC/immun-pbmc-fm/model_8_sparse_data_diffusion/plans/paired_finetune_intradataset_20260927/README.md"
464
+ },
465
+ {
466
+ "value": "P/C definition: precision/coverage/density (PCA-50 + k = 10 balls fitted on the scored donors' observed R1 cells); PCA components in every summary.json = 50",
467
+ "source": "/home/sj_server_1/PBISC/immun-pbmc-fm/model_8_sparse_data_diffusion/plans/paired_finetune_intradataset_20260927/tools/score_ft.py"
468
+ }
469
+ ]
470
+ },
471
+ {
472
+ "kind": "content",
473
+ "section": "9",
474
+ "section_label": "9 Paired validation",
475
+ "sec09_index": 2,
476
+ "title": "5 donors: LoRA vs scSemiProfiler — disease signal",
477
+ "layout": "figure_keywords",
478
+ "figures": [
479
+ "figures/sec09_fewpair_disease.png"
480
+ ],
481
+ "keywords": [
482
+ "Top-50 DEG: LoRA-5 higher 3/4; Ji ~0",
483
+ "logFC r: scSemi-5 wins Giroux; Sepsis split",
484
+ "Giroux: real-bulk broadcast beats all arms"
485
+ ],
486
+ "footnote": "Same draws as previous slide. Top-50 DEG = Welch + BH overlap, summed over 5 cell types.",
487
+ "footnote_full": "Same draws and verdict rule as the previous slide; DEG tie = half the draws equal or mean gap < 1 gene. logFC r = mean over T/B/Mono/NK of case-vs-control log2FC r (generated vs observed); top-50 DEG = Welch+BH overlap summed over 5 types (max 250; Giroux 51–109, Ji 75–250 per draw). Giroux test = 2 vs 2 subjects per draw. Broadcast = the input real bulk's own logFC. Scores: scores/<cohort>/fewshot_n5/draw<j>{,_scsemi5}/.",
488
+ "sources": "tools/sec09_paired_validation.py; data/sec09_fewpair_disease.csv, data/sec09_slide_text.json",
489
+ "numbers": [
490
+ {
491
+ "value": "Top-50 DEG LoRA-5 vs scSemi-5 (shared-draw means; LoRA-better / tied draws; verdict): Sepsis 16.4 vs 5.2 (5/5, 0 tied, lora); Imperial 113.6 vs 46.8 (5/5, 0 tied, lora); Giroux 11.6 vs 1.2 (5/5, 0 tied, lora); Ji 0.2 vs 0.0 (1/5, 4 tied, tie)",
492
+ "source": "/home/sj_server_1/PBISC/immun-pbmc-fm/model_8_sparse_data_diffusion/plans/paired_finetune_intradataset_20260927/scores/<cohort>/fewshot_n5/draw<j>{,_scsemi5}/summary.json and contrast.csv"
493
+ },
494
+ {
495
+ "value": "logFC r LoRA-5 vs scSemi-5 (shared-draw means; LoRA-better draws; verdict): Sepsis 0.350 vs 0.402 (3/5, split); Imperial 0.749 vs 0.562 (5/5, lora); Giroux 0.331 vs 0.398 (0/5, scsemi); Ji 0.333 vs 0.153 (5/5, lora)",
496
+ "source": "/home/sj_server_1/PBISC/immun-pbmc-fm/model_8_sparse_data_diffusion/plans/paired_finetune_intradataset_20260927/scores/<cohort>/fewshot_n5/draw<j>{,_scsemi5}/summary.json and contrast.csv"
497
+ },
498
+ {
499
+ "value": "Giroux broadcast logFC r 0.539 vs best arm 0.398; broadcast DEG 25.4 vs best arm 11.6 (means over all draws)",
500
+ "source": "/home/sj_server_1/PBISC/immun-pbmc-fm/model_8_sparse_data_diffusion/plans/paired_finetune_intradataset_20260927/scores/giroux2022/fewshot_n5/draw<j>{,_scsemi5}/summary.json"
501
+ },
502
+ {
503
+ "value": "DEG maximum per draw: Sepsis 250, Imperial 250, Giroux 51–109, Ji 75–250",
504
+ "source": "/home/sj_server_1/PBISC/immun-pbmc-fm/model_8_sparse_data_diffusion/plans/paired_finetune_intradataset_20260927/scores/<cohort>/fewshot_n5/draw<j>/summary.json (deg_top50_max)"
505
+ },
506
+ {
507
+ "value": "Giroux test subjects per draw: 2 vs 2 (moderate vs mild); test pairs 10–12",
508
+ "source": "/home/sj_server_1/PBISC/immun-pbmc-fm/model_8_sparse_data_diffusion/plans/paired_finetune_intradataset_20260927/data/giroux2022/fewshot_n5/DRAWS.json (train_donors); /home/sj_server_1/PBISC/immun-pbmc-fm/model_8_sparse_data_diffusion/plans/paired_finetune_intradataset_20260927/data/giroux2022/folds.csv (group)"
509
+ }
510
+ ]
511
+ },
512
+ {
513
+ "kind": "content",
514
+ "section": "9",
515
+ "section_label": "9 Paired validation",
516
+ "sec09_index": 3,
517
+ "title": "All pairs, 5-fold",
518
+ "layout": "full",
519
+ "figures": [
520
+ "figures/sec09_fivefold.png"
521
+ ],
522
+ "keywords": [
523
+ "LoRA tops coverage 5/5, logFC r 4/4",
524
+ "Ji whole blood: baselines 0.11, LoRA 0.86",
525
+ "Giroux: broadcast r 0.64 > LoRA 0.50"
526
+ ],
527
+ "footnote": "Donor-level 5-fold CV; each pair scored by a model that never saw its donor.",
528
+ "footnote_full": "Donor-level 5-fold CV; each pair scored once, by the fold model that never trained on its donor (one pooled call per cohort). LoRA r=16 on all training donors' real bulk, early stop on inner-val donors; sc-only = full fine-tune on training donors' sc pseudobulk, calibrated input. Base f01 6k·1x·E16. Top-50 DEG: LoRA best 4/4. Sepsis DEG from pooled_deg. Scores: scores/<cohort>/pooled/summary.json.",
529
+ "sources": "tools/sec09_paired_validation.py; data/sec09_fivefold.csv, data/sec09_slide_text.json",
530
+ "numbers": [
531
+ {
532
+ "value": "LoRA best of 3 arms: coverage 5/5, logFC r 4/4, top-50 DEG 4/4",
533
+ "source": "/home/sj_server_1/PBISC/immun-pbmc-fm/model_8_sparse_data_diffusion/plans/paired_finetune_intradataset_20260927/scores/<cohort>/pooled/summary.json (Sepsis DEG: /home/sj_server_1/PBISC/immun-pbmc-fm/model_8_sparse_data_diffusion/plans/paired_finetune_intradataset_20260927/scores/ye2026_sepsis/pooled_deg/summary.json)"
534
+ },
535
+ {
536
+ "value": "Ji coverage: zero-shot cal 0.106, sc-only 0.113, LoRA 0.857",
537
+ "source": "/home/sj_server_1/PBISC/immun-pbmc-fm/model_8_sparse_data_diffusion/plans/paired_finetune_intradataset_20260927/scores/ji2025_chili/pooled/summary.json"
538
+ },
539
+ {
540
+ "value": "Giroux logFC r: broadcast 0.638 vs LoRA 0.504; DEG broadcast 39 vs LoRA 25",
541
+ "source": "/home/sj_server_1/PBISC/immun-pbmc-fm/model_8_sparse_data_diffusion/plans/paired_finetune_intradataset_20260927/scores/giroux2022/pooled/summary.json"
542
+ },
543
+ {
544
+ "value": "LoRA logFC r vs broadcast: Sepsis 0.527 vs 0.316, Imperial 0.819 vs 0.661, Giroux 0.504 vs 0.638, Ji 0.479 vs 0.240",
545
+ "source": "/home/sj_server_1/PBISC/immun-pbmc-fm/model_8_sparse_data_diffusion/plans/paired_finetune_intradataset_20260927/scores/<cohort>/pooled/summary.json (Sepsis DEG: /home/sj_server_1/PBISC/immun-pbmc-fm/model_8_sparse_data_diffusion/plans/paired_finetune_intradataset_20260927/scores/ye2026_sepsis/pooled_deg/summary.json)"
546
+ },
547
+ {
548
+ "value": "Pooled n (pairs / donors): ImMicro 107/107, Sepsis 82/82, Imperial 157/57, Giroux 24/9, Ji 33/20",
549
+ "source": "/home/sj_server_1/PBISC/immun-pbmc-fm/model_8_sparse_data_diffusion/plans/paired_finetune_intradataset_20260927/scores/<cohort>/pooled/summary.json (n_donors); /home/sj_server_1/PBISC/immun-pbmc-fm/model_8_sparse_data_diffusion/plans/paired_finetune_intradataset_20260927/data/<cohort>/fewshot_n5/DRAWS.json"
550
+ },
551
+ {
552
+ "value": "early stopping: About 10 % of each fold's training donors are inner-validation, used only for early stopping",
553
+ "source": "/home/sj_server_1/PBISC/immun-pbmc-fm/model_8_sparse_data_diffusion/plans/paired_finetune_intradataset_20260927/README.md"
554
+ }
555
+ ]
556
+ },
557
+ {
558
+ "kind": "content",
559
+ "section": "10",
560
+ "section_label": "10 Paired-subset cohorts",
561
+ "title": "Next: cohorts with a paired subset (planned)",
562
+ "layout": "figure_keywords",
563
+ "figures": [
564
+ "figures/sec10_paired_subset_cohorts.png"
565
+ ],
566
+ "keywords": [
567
+ "Train LoRA on pairs, generate bulk-only",
568
+ "Sepsis controls: 21 paired + 54 bulk-only",
569
+ "ChILI pre-ICI: 11 bulk, 4 unpaired sc"
570
+ ],
571
+ "footnote": "Counts from pairing manifests. Model: f01 6k 1x E16 + LoRA r16.",
572
+ "say": "Planned: no LoRA cells exist yet for any bulk-only sample. Ji bulk is PAXgene whole blood. Only 7 of the Arunachalam pairs are strict same-visit pairs. Asan is omitted because it has no donor map.",
573
+ "sources": "tools/sec10_paired_subset_cohorts.py; data/sec10_cohort_counts.csv, data/sec10_bulk_only_groups.csv, data/sec10_quoted_numbers.csv",
574
+ "footnote_full": "Counts from pairing manifests. QC = identity check (Imperial also >=200 cells); sex-flag = bulk sex differs from metadata or is ambiguous. Not shown: Asan (no donor map), Giroux (24 pairs, 17 bulk-only; broadcast beats LoRA). Model: f01 6k 1x E16 + LoRA r16."
575
+ },
576
+ {
577
+ "kind": "divider",
578
+ "title": "Backup"
579
+ },
580
+ {
581
+ "kind": "content",
582
+ "section": "4",
583
+ "section_label": "Backup · 4 SLE benchmark",
584
+ "backup": true,
585
+ "title": "Bulk broadcast baseline",
586
+ "layout": "full",
587
+ "figures": [
588
+ "figures/sec04_sle_broadcast.png"
589
+ ],
590
+ "keywords": [
591
+ "Bulk logFC copied: r 0.68 vs 0.37",
592
+ "Type-specific part: partial r 0.21",
593
+ "PBISC-VAE same; scSemiProfiler 0.17"
594
+ ],
595
+ "footnote": "SLE, 42 donors, 1,006 genes. Partial r: both logFCs residualised on bulk logFC.",
596
+ "sources": "tools/sec04_sle_benchmark.py; data/sec04_sle_broadcast.csv, data/sec04_sle_numbers.csv",
597
+ "footnote_full": "SLE held-out, 42 donors, 1,006 genes; PBISC 5 seeds. Partial r: truth and method logFC residualised on bulk logFC. Broadcast has no residual, so it is not scored. Split-half and BayesPrism checks: sle_broadcast/RESULTS.md."
598
+ },
599
+ {
600
+ "kind": "content",
601
+ "section": "5",
602
+ "section_label": "Backup · 5 Real bulk vs pseudobulk",
603
+ "backup": true,
604
+ "title": "Same shift in three paired cohorts",
605
+ "layout": "full",
606
+ "figures": [
607
+ "figures/sec05_shift_cohorts.png"
608
+ ],
609
+ "keywords": [
610
+ "Shared shift in all 3 cohorts"
611
+ ],
612
+ "footnote": "Model inputs only, no generation. PCA fitted per cohort on sc pseudobulks.",
613
+ "sources": "tools/sec05_shift_cohorts.py; data/sec05_shift_cohorts.csv",
614
+ "footnote_full": "Model inputs only, no generation. PCA is fitted on each cohort's sc pseudobulks (Arunachalam: 11 PCs, n = 12). D uses same-condition pairs only for Randolph and Arunachalam. Shift removal is a leave-one-out diagnostic."
615
+ },
616
+ {
617
+ "kind": "content",
618
+ "section": "6",
619
+ "section_label": "Backup · 6 Paired fine-tuning",
620
+ "backup": true,
621
+ "title": "Evaluation design",
622
+ "layout": "full",
623
+ "figures": [
624
+ "figures/sec06_eval_design.png"
625
+ ],
626
+ "keywords": [
627
+ "Donor-level splits; test donors never trained",
628
+ "5-fold: other folds · few: 5 donors",
629
+ "Giroux few-pair trains 12–14 of 24 pairs"
630
+ ],
631
+ "footnote": "Bars: Ye 2026 sepsis. QC-failed pairs excluded.",
632
+ "sources": "tools/sec06_finetune_method.py; data/sec06_eval_design.csv, data/sec06_eval_design_sepsis_roles.csv",
633
+ "footnote_full": "Counts: data/<cohort>/folds.csv and fewshot_n5/DRAWS.json; QC-failed pairs (fold −1) excluded. Bars: Ye 2026 sepsis."
634
+ }
635
+ ]
636
+ }