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paper-releases/pbisc-diffusion/updates/20261006T145850Z-deck-six-figure-order/diffusion/dataset/server_1/model8/presentations/2026-09-30--paper-summary--r00/data/figure_plan.json ADDED
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+ {
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+ "source": "Nature Style Manuscript Writing.pdf (paper-release-20260928/reference-papers, 2026-10-06): six main figures, up to 17 supplementary; short abstract and introduction, descriptive results, short discussion with limitations, detailed methods. LoRA results on the healthy cohort in Fig. 2; the disease cohort kept for Fig. 4.",
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+ "status_legend": {
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+ "Ready": "slide exists and fits the panel",
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+ "Adapt": "slide exists; change its scope or style",
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+ "Draft": "new draft exists, not yet approved",
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+ "Build": "results exist; no slide yet",
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+ "Run": "needs a new analysis or experiment",
9
+ "Decide": "needs an author decision"
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+ },
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+ "figures": [
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+ {
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+ "n": 1,
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+ "title": "Design and performance of PBISC",
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+ "claim": "Diffusion on each gene's value and detection, conditioned on bulk, writes realistic blood cells.",
16
+ "panels": [
17
+ {"p": "a", "content": "Backbones compared: scDiffusion, SDD, PBISC-Diffusion", "evidence": ["Backbone: SDD → PBISC-Diffusion"], "status": "Ready"},
18
+ {"p": "b", "content": "Overview: pretraining, diffusion, generation", "evidence": ["Overview draft (Nature style)"], "status": "Draft"},
19
+ {"p": "c", "content": "What the bulk condition contains", "evidence": ["Bulk conditioning"], "status": "Ready"},
20
+ {"p": "d", "content": "Pretraining corpus: assays, conditions, cell types", "evidence": ["Pretraining corpus"], "status": "Ready"},
21
+ {"p": "e", "content": "Width and context: lower loss, same biology", "evidence": ["Width & context ablation: loss saturation", "Width & context ablation: benchmark"], "status": "Ready"},
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+ {"p": "f", "content": "Gene panel: 2k, 3k, 6k, 15k", "evidence": ["Gene context: 2k / 3k / 6k / 15k"], "status": "Ready"},
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+ {"p": "g", "content": "How generated cells are scored", "evidence": ["How we score generated cells"], "status": "Ready", "note": "may move to Methods"}
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+ ],
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+ "details": ["PBISC-Diffusion: bulk in, cells out", "Denoiser: joint value + support diffusion"]
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+ },
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+ {
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+ "n": 2,
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+ "title": "Fine-tuning PBISC with LoRA",
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+ "claim": "Real bulk is not pseudobulk; a few paired samples and a LoRA of minutes close the gap.",
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+ "panels": [
32
+ {"p": "a", "content": "Real bulk differs from the training input", "evidence": ["Real bulk ≠ pseudobulk (model input)", "Same shift in three paired cohorts"], "status": "Ready"},
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+ {"p": "b", "content": "Without fine-tuning, cells fall off the real manifold", "evidence": ["Consequence: cells off-manifold"], "status": "Ready"},
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+ {"p": "c", "content": "LoRA on paired bulk and cells; how it is tested", "evidence": ["Fine-tuning with paired bulk + sc", "Evaluation design"], "status": "Ready"},
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+ {"p": "d", "content": "Full, LoRA and condition-encoder fine-tuning", "evidence": ["Full vs LoRA vs cond.-encoder-only"], "status": "Adapt", "note": "healthy cohort (ImMicro) only"},
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+ {"p": "e", "content": "How many pairs are needed", "evidence": ["Pairs needed: composition, coverage, training steps"], "status": "Adapt", "note": "healthy cohort only"},
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+ {"p": "f", "content": "LoRA rank and K choices", "evidence": ["LoRA rank: r = 4, 16, 64", "K diversification: no gain"], "status": "Ready", "note": "supplementary candidate"}
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+ ],
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+ "details": []
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+ },
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+ {
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+ "n": 3,
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+ "title": "Comparison with other methods",
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+ "claim": "PBISC beats scSemiProfiler on cells and composition, with far less compute.",
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+ "panels": [
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+ {"p": "a", "content": "Lupus benchmark against scSemiProfiler", "evidence": ["SLE benchmark: PBISC vs scSemiProfiler", "SLE benchmark: per cell type", "Bulk broadcast baseline"], "status": "Ready"},
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+ {"p": "b", "content": "Five paired cohorts", "evidence": ["Five paired cohorts"], "status": "Ready"},
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+ {"p": "c", "content": "Five donors: generated cells", "evidence": ["5 donors: LoRA vs scSemiProfiler — cells", "5 donors: realism beyond precision/coverage", "5 donors: precision/coverage at k = 3, 5, 10"], "status": "Ready"},
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+ {"p": "d", "content": "scSemiProfiler copies its representative", "evidence": ["scSemiProfiler copies its representative"], "status": "Ready"},
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+ {"p": "e", "content": "Same training pairs, 5-fold", "evidence": ["5-fold CV: train on the other 4 folds", "Same training pairs: LoRA vs scSemiProfiler", "5-fold: realism beyond precision/coverage"], "status": "Ready", "note": "scSemiProfiler CV still running for some cohorts"},
51
+ {"p": "f", "content": "Time to apply to a new cohort", "evidence": ["5 donors: time to apply"], "status": "Ready"},
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+ {"p": "g", "content": "CYBERSORTx and other methods", "evidence": [], "status": "Run", "note": "CYBERSORTx not run yet"},
53
+ {"p": "h", "content": "PBISC-VAE as a comparator", "evidence": [], "status": "Decide", "note": "dropped from the story on 2026-09-30; the guide lists it"}
54
+ ],
55
+ "details": []
56
+ },
57
+ {
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+ "n": 4,
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+ "title": "Disease signal and rare cell states",
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+ "claim": "On a disease cohort, generated cells carry cell-type disease effects and rare disease states.",
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+ "panels": [
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+ {"p": "a", "content": "Sepsis: disease effect against pairs used", "evidence": ["Pairs needed: donor and disease signal"], "status": "Ready"},
63
+ {"p": "b", "content": "Disease signal against scSemiProfiler", "evidence": ["5 donors: LoRA vs scSemiProfiler — disease signal", "Disease genes at every list length (CAT)"], "status": "Ready"},
64
+ {"p": "c", "content": "Rare disease states in held-out sepsis (MS1, C1Q-high, ISG-high T)", "evidence": [], "status": "Build", "note": "plans/rare_states_screen_20261004"},
65
+ {"p": "d", "content": "More cells per bulk for rare states (K = 1,000 vs 4,000 or more)", "evidence": [], "status": "Run", "note": "the guide's open question; K = 4,000 runs exist for bulk-only samples"}
66
+ ],
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+ "details": []
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+ },
69
+ {
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+ "n": 5,
71
+ "title": "Datasets outside training",
72
+ "claim": "PBISC applies to cohorts it never saw, and needs their own pairs to do it well.",
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+ "panels": [
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+ {"p": "a", "content": "Other cohorts' pairs do not replace a cohort's own", "evidence": ["Pairs from other cohorts do not transfer", "Longer training on other cohorts: gap stays"], "status": "Ready"},
75
+ {"p": "b", "content": "Behçet: disease direction from real bulk", "evidence": ["Consequence: disease direction flips"], "status": "Adapt", "note": "add the LoRA-3 result (C1Q-high BD > HC)"},
76
+ {"p": "c", "content": "Influenza exposure from raw clinical bulk (Randolph)", "evidence": [], "status": "Build", "note": "manuscript result, r = 0.64"},
77
+ {"p": "d", "content": "Diseases absent from the corpus (Kawasaki, SLE) vs present (DRESS)", "evidence": [], "status": "Build", "note": "results of 2026-10-04"}
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+ ],
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+ "details": []
80
+ },
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+ {
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+ "n": 6,
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+ "title": "Discovery from public bulk-only data",
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+ "claim": "Cells generated for bulk-only samples test reported cell populations at cohort scale.",
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+ "panels": [
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+ {"p": "a", "content": "Bulk-only samples in the paired cohorts", "evidence": ["Next: cohorts with a paired subset (planned)"], "status": "Ready"},
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+ {"p": "b", "content": "Cells for 122 sepsis and 164 Imperial bulk-only samples", "evidence": [], "status": "Run", "note": "K = 1,000 found no population beyond bulk; K = 4,000 pending"},
88
+ {"p": "c", "content": "Reported populations to test (Ye 2025, Stephenson 2025, Arunachalam 2020)", "evidence": [], "status": "Run"},
89
+ {"p": "d", "content": "Outlook: other tissues from a few dozen pairs", "evidence": ["Next: other tissues from a few dozen pairs"], "status": "Ready", "note": "Discussion"}
90
+ ],
91
+ "details": []
92
+ }
93
+ ],
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+ "supplementary": ["No pretraining: same cohort, from scratch", "No pretraining: other cohorts, from scratch", "Rare states: from scratch vs pretrained"],
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+ "appendix": ["Appendix: scSemiProfiler without output threshold"]
96
+ }
paper-releases/pbisc-diffusion/updates/20261006T145850Z-deck-six-figure-order/diffusion/dataset/server_1/model8/presentations/2026-09-30--paper-summary--r00/data/figure_plan_slide_text.json ADDED
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+ {
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+ "section": "figure-plan",
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+ "scripts": [
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+ "/home/sj_server_1/PBISC/immun-pbmc-fm/model_8_sparse_data_diffusion/presentations/2026-09-30--paper-summary--r00/tools/figure_plan.py"
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+ ],
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+ "generated_from": "tools/figure_plan.py (rerun to refresh; do not edit by hand)",
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+ "slides": [
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+ {
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+ "title": "Manuscript plan: six main figures",
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+ "layout": "full",
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+ "figures": [
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+ "/home/sj_server_1/PBISC/immun-pbmc-fm/model_8_sparse_data_diffusion/presentations/2026-09-30--paper-summary--r00/figures/figplan_overview.png"
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+ ],
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+ "keywords": [],
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+ "footnote_short": "Nature style: short abstract and introduction, descriptive results, short discussion, detailed methods; up to 17 supplementary figures.",
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+ "footnote": "Nature Style Manuscript Writing.pdf (paper-release-20260928/reference-papers, 2026-10-06): six main figures, up to 17 supplementary; short abstract and introduction, descriptive results, short discussion with limitations, detailed methods. LoRA results on the healthy cohort in Fig. 2; the disease cohort kept for Fig. 4. Status: Ready = slide exists and fits the panel; Adapt = slide exists; change its scope or style; Draft = new draft exists, not yet approved; Build = results exist; no slide yet; Run = needs a new analysis or experiment; Decide = needs an author decision.",
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+ "numbers": []
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+ },
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+ {
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+ "title": "Figure 1 plan: Design and performance of PBISC",
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+ "layout": "full",
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+ "figures": [
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+ "/home/sj_server_1/PBISC/immun-pbmc-fm/model_8_sparse_data_diffusion/presentations/2026-09-30--paper-summary--r00/figures/figplan_fig1.png"
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+ ],
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+ "keywords": [],
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+ "footnote_short": "Diffusion on each gene's value and detection, conditioned on bulk, writes realistic blood cells. 6 of 7 panels ready.",
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+ "footnote": "Panels: a) Backbones compared: scDiffusion, SDD, PBISC-Diffusion [Ready]. b) Overview: pretraining, diffusion, generation [Draft]. c) What the bulk condition contains [Ready]. d) Pretraining corpus: assays, conditions, cell types [Ready]. e) Width and context: lower loss, same biology [Ready]. f) Gene panel: 2k, 3k, 6k, 15k [Ready]. g) How generated cells are scored [Ready; may move to Methods]. Details in this section: PBISC-Diffusion: bulk in, cells out; Denoiser: joint value + support diffusion.",
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+ "numbers": []
29
+ },
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+ {
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+ "title": "Figure 2 plan: Fine-tuning PBISC with LoRA",
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+ "layout": "full",
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+ "figures": [
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+ "/home/sj_server_1/PBISC/immun-pbmc-fm/model_8_sparse_data_diffusion/presentations/2026-09-30--paper-summary--r00/figures/figplan_fig2.png"
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+ ],
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+ "keywords": [],
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+ "footnote_short": "Real bulk is not pseudobulk; a few paired samples and a LoRA of minutes close the gap. 4 of 6 panels ready.",
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+ "footnote": "Panels: a) Real bulk differs from the training input [Ready]. b) Without fine-tuning, cells fall off the real manifold [Ready]. c) LoRA on paired bulk and cells; how it is tested [Ready]. d) Full, LoRA and condition-encoder fine-tuning [Adapt; healthy cohort (ImMicro) only]. e) How many pairs are needed [Adapt; healthy cohort only]. f) LoRA rank and K choices [Ready; supplementary candidate].",
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+ "numbers": []
40
+ },
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+ {
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+ "title": "Figure 3 plan: Comparison with other methods",
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+ "layout": "full",
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+ "figures": [
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+ "/home/sj_server_1/PBISC/immun-pbmc-fm/model_8_sparse_data_diffusion/presentations/2026-09-30--paper-summary--r00/figures/figplan_fig3.png"
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+ ],
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+ "keywords": [],
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+ "footnote_short": "PBISC beats scSemiProfiler on cells and composition, with far less compute. 6 of 8 panels ready.",
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+ "footnote": "Panels: a) Lupus benchmark against scSemiProfiler [Ready]. b) Five paired cohorts [Ready]. c) Five donors: generated cells [Ready]. d) scSemiProfiler copies its representative [Ready]. e) Same training pairs, 5-fold [Ready; scSemiProfiler CV still running for some cohorts]. f) Time to apply to a new cohort [Ready]. g) CYBERSORTx and other methods [Run; CYBERSORTx not run yet]. h) PBISC-VAE as a comparator [Decide; dropped from the story on 2026-09-30; the guide lists it].",
50
+ "numbers": []
51
+ },
52
+ {
53
+ "title": "Figure 4 plan: Disease signal and rare cell states",
54
+ "layout": "full",
55
+ "figures": [
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+ "/home/sj_server_1/PBISC/immun-pbmc-fm/model_8_sparse_data_diffusion/presentations/2026-09-30--paper-summary--r00/figures/figplan_fig4.png"
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+ ],
58
+ "keywords": [],
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+ "footnote_short": "On a disease cohort, generated cells carry cell-type disease effects and rare disease states. 2 of 4 panels ready.",
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+ "footnote": "Panels: a) Sepsis: disease effect against pairs used [Ready]. b) Disease signal against scSemiProfiler [Ready]. c) Rare disease states in held-out sepsis (MS1, C1Q-high, ISG-high T) [Build; plans/rare_states_screen_20261004]. d) More cells per bulk for rare states (K = 1,000 vs 4,000 or more) [Run; the guide's open question; K = 4,000 runs exist for bulk-only samples].",
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+ "numbers": []
62
+ },
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+ {
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+ "title": "Figure 5 plan: Datasets outside training",
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+ "layout": "full",
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+ "figures": [
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+ "/home/sj_server_1/PBISC/immun-pbmc-fm/model_8_sparse_data_diffusion/presentations/2026-09-30--paper-summary--r00/figures/figplan_fig5.png"
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+ ],
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+ "keywords": [],
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+ "footnote_short": "PBISC applies to cohorts it never saw, and needs their own pairs to do it well. 1 of 4 panels ready.",
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+ "footnote": "Panels: a) Other cohorts' pairs do not replace a cohort's own [Ready]. b) Behçet: disease direction from real bulk [Adapt; add the LoRA-3 result (C1Q-high BD > HC)]. c) Influenza exposure from raw clinical bulk (Randolph) [Build; manuscript result, r = 0.64]. d) Diseases absent from the corpus (Kawasaki, SLE) vs present (DRESS) [Build; results of 2026-10-04].",
72
+ "numbers": []
73
+ },
74
+ {
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+ "title": "Figure 6 plan: Discovery from public bulk-only data",
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+ "layout": "full",
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+ "figures": [
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+ "/home/sj_server_1/PBISC/immun-pbmc-fm/model_8_sparse_data_diffusion/presentations/2026-09-30--paper-summary--r00/figures/figplan_fig6.png"
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+ ],
80
+ "keywords": [],
81
+ "footnote_short": "Cells generated for bulk-only samples test reported cell populations at cohort scale. 2 of 4 panels ready.",
82
+ "footnote": "Panels: a) Bulk-only samples in the paired cohorts [Ready]. b) Cells for 122 sepsis and 164 Imperial bulk-only samples [Run; K = 1,000 found no population beyond bulk; K = 4,000 pending]. c) Reported populations to test (Ye 2025, Stephenson 2025, Arunachalam 2020) [Run]. d) Outlook: other tissues from a few dozen pairs [Ready; Discussion].",
83
+ "numbers": []
84
+ },
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+ {
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+ "title": "Overview draft (Nature style)",
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+ "layout": "full",
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+ "figures": [
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+ "/home/sj_server_1/PBISC/immun-pbmc-fm/model_8_sparse_data_diffusion/presentations/2026-09-30--paper-summary--r00/figures/fig1b_overview_nature.png"
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+ ],
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+ "keywords": [
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+ "Each cell is learned with its own bulk",
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+ "Diffusion on each gene's value and detection",
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+ "One bulk in, K cells out; optional LoRA"
95
+ ],
96
+ "footnote_short": "Draft for Fig. 1b; schematic, no data. Plan: manuscript editorial/fig1_nature_redesign_plan.",
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+ "footnote": "Candidate replacement for the engineering diagram (kept in this section as details and for Methods). Source: paper-release-20260928/manuscript/figures/fig01_architecture_nature.svg (scripts/build_figure1_architecture_nature.py).",
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+ "numbers": []
99
+ },
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+ {
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+ "title": "Pretraining corpus",
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+ "layout": "full",
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+ "figures": [
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+ "/home/sj_server_1/PBISC/immun-pbmc-fm/model_8_sparse_data_diffusion/presentations/2026-09-30--paper-summary--r00/figures/fig1d_corpus.png"
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+ ],
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+ "keywords": [
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+ "41.4 M cells, 22 datasets, 3,199 donors",
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+ "88.5% healthy donors; 23.6% cultured in vitro",
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+ "Labels describe the corpus; never model input"
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+ ],
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+ "footnote_short": "Detailed version: Supplementary Fig. S1 of the manuscript.",
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+ "footnote": "Source: paper-release-20260928/manuscript/source_data/corpus/ (build_corpus_tables.py) and figures/fig01_corpus_nature.png (build_figure1_corpus.py).",
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+ "numbers": [
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+ {
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+ "value": "41,395,184 cells; 22 datasets; 3,199 donors; healthy 88.5%; in vitro 23.6%",
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+ "source": "manuscript/source_data/corpus/corpus_summary.json"
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+ }
118
+ ]
119
+ }
120
+ ]
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+ }
paper-releases/pbisc-diffusion/updates/20261006T145850Z-deck-six-figure-order/diffusion/dataset/server_1/model8/presentations/2026-09-30--paper-summary--r00/data/sec09_time_to_apply_slide_text.json ADDED
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+ {
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+ "section": "09-time",
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+ "scripts": [
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+ "/home/sj_server_1/PBISC/immun-pbmc-fm/model_8_sparse_data_diffusion/presentations/2026-09-30--paper-summary--r00/tools/sec09_time_to_apply.py"
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+ ],
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+ "generated_from": "tools/sec09_time_to_apply.py (rerun to refresh; do not edit by hand)",
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+ "slides": [
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+ {
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+ "title": "5 donors: time to apply",
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+ "layout": "full",
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+ "figures": [
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+ "/home/sj_server_1/PBISC/immun-pbmc-fm/model_8_sparse_data_diffusion/presentations/2026-09-30--paper-summary--r00/figures/sec09_time_to_apply.png"
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+ ],
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+ "keywords": [
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+ "LoRA-5: 3–11 min per draw, every test sample",
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+ "scSemiProfiler-5: 57 min–4.1 h per draw",
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+ "17–59× less GPU time, same 5 donors"
18
+ ],
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+ "footnote_short": "One GB10 GPU; mean of 5 draws. Data prep and scoring not counted. PBISC pretraining (15.9 h) is done once.",
20
+ "footnote": "Same 25 draws as the '5 donors' slides (5 cohorts x 5 draws; same 5 training donors and test samples for both methods). GPU time on one GB10, every step alone on the GPU (shared lock). LoRA-5: fine-tune = RUN.json wall_seconds of the 3,000-step LoRA; generate = wall clock of the sampling job in the queue log (model load + DDIM 50, 1,500 cells per test sample). scSemiProfiler-5 (upstream c2aea02, default budget): stage 1 + stage 2 pretraining of every representative (model receipts) + its per-target inference (5 ministages x 150 epochs, export receipt total_target_seconds). Not counted on either side: CPU data preparation, scoring, work lost to interruptions, and PBISC's one-time pretraining (15.9 h; 'Fine-tuning with paired bulk + sc' slide), which every cohort reuses. scSemiProfiler time grows with the number of test samples because it trains one model per sample. Per-draw ratio scSemiProfiler / LoRA: ImMicro 15–19×; Sepsis 26–47×; Imperial 19–26×; Giroux 54–63×; Ji 11–20× (all 25 draws 11–63×; keyword and figure = mean of each cohort's 5 draws).",
21
+ "numbers": [
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+ {
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+ "value": "ImMicro: LoRA-5 8.4 min (fine-tune 1.9 + generate 6.5), scSemiProfiler-5 141 min (representatives 15 + per-sample models 126); 15–19× per draw; per test sample 4.9 s vs 83 s",
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+ "source": "data/sec09_time_to_apply.csv"
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+ },
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+ {
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+ "value": "Sepsis: LoRA-5 6.7 min (fine-tune 1.8 + generate 4.9), scSemiProfiler-5 244 min (representatives 30 + per-sample models 214); 26–47× per draw; per test sample 5.2 s vs 190 s",
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+ "source": "data/sec09_time_to_apply.csv"
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+ },
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+ {
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+ "value": "Imperial: LoRA-5 10.8 min (fine-tune 1.8 + generate 9.0), scSemiProfiler-5 229 min (representatives 32 + per-sample models 197); 19–26× per draw; per test sample 4.5 s vs 96 s",
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+ "source": "data/sec09_time_to_apply.csv"
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+ },
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+ {
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+ "value": "Giroux: LoRA-5 2.6 min (fine-tune 1.9 + generate 0.7), scSemiProfiler-5 156 min (representatives 117 + per-sample models 38); 54–63× per draw; per test sample 14.8 s vs 872 s",
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+ "source": "data/sec09_time_to_apply.csv"
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+ },
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+ {
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+ "value": "Ji: LoRA-5 3.4 min (fine-tune 1.8 + generate 1.6), scSemiProfiler-5 57 min (representatives 24 + per-sample models 33); 11–20× per draw; per test sample 8.1 s vs 137 s",
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+ "source": "data/sec09_time_to_apply.csv"
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+ },
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+ {
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+ "value": "PBISC one-time pretraining 15.9 h (not counted per draw)",
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+ "source": "data/sec06_ft_method.csv (pretrain_wall_hours)"
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+ }
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+ ]
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+ }
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+ ]
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+ }
paper-releases/pbisc-diffusion/updates/20261006T145850Z-deck-six-figure-order/diffusion/dataset/server_1/model8/presentations/2026-09-30--paper-summary--r00/figures/sec09_time_to_apply.pdf ADDED
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