| const pptxgen = require("pptxgenjs"); |
|
|
| const pres = new pptxgen(); |
| pres.layout = "LAYOUT_16x9"; |
| pres.author = "Qian"; |
| pres.title = "GRN-Guided Cascaded Flow Matching"; |
|
|
| |
| const C = { |
| navy: "0B1D3A", |
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| textMid: "475569", |
| accent1: "3B82F6", |
| accent2: "F59E0B", |
| accent3: "10B981", |
| subtitleOnDark: "A7F3D0", |
| }; |
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| |
| function addSlideNum(slide, num) { |
| slide.addText(String(num), { |
| x: 9.3, y: 5.2, w: 0.5, h: 0.3, |
| fontSize: 8, color: C.midGray, align: "right", fontFace: "Calibri", |
| }); |
| } |
|
|
| |
| function addDividerSlide(title, subtitle, num) { |
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| fontSize: 36, fontFace: "Georgia", color: C.white, bold: true, margin: 0, |
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| if (subtitle) { |
| s.addText(subtitle, { |
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| addSlideNum(s, num); |
| return s; |
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|
|
| |
| function addContentSlide(title, num) { |
| const s = pres.addSlide(); |
| s.background = { color: C.offWhite }; |
| s.addShape(pres.shapes.RECTANGLE, { x: 0, y: 0, w: 10, h: 0.06, fill: { color: C.teal } }); |
| s.addText(title, { |
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| fontSize: 22, fontFace: "Georgia", color: C.textDark, bold: true, margin: 0, |
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| addSlideNum(s, num); |
| return s; |
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|
|
| let slideNum = 0; |
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| |
| |
| |
| slideNum++; |
| { |
| const s = pres.addSlide(); |
| s.background = { color: C.navy }; |
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|
|
| s.addText("GRN-Guided\nCascaded Flow Matching\nfor Single-Cell Perturbation Prediction", { |
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|
|
| s.addText("Gene Regulatory Network meets Flow Matching", { |
| x: 0.7, y: 3.75, w: 8.6, h: 0.4, |
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|
|
| s.addShape(pres.shapes.RECTANGLE, { x: 0.7, y: 4.35, w: 2.5, h: 0.02, fill: { color: C.midGray } }); |
|
|
| s.addText("Group Meeting | 2026.03", { |
| x: 0.7, y: 4.5, w: 8.6, h: 0.4, |
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| }); |
| addSlideNum(s, slideNum); |
| } |
|
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| |
| |
| |
| slideNum++; |
| addDividerSlide("1. Task", "Single-Cell Perturbation Prediction", slideNum); |
|
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| |
| |
| |
| slideNum++; |
| { |
| const s = addContentSlide("Virtual Cell & Perturbation Types", slideNum); |
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| |
| s.addShape(pres.shapes.RECTANGLE, { x: 0.5, y: 0.9, w: 4.2, h: 1.15, fill: { color: C.white }, shadow: cardShadow() }); |
| s.addShape(pres.shapes.RECTANGLE, { x: 0.5, y: 0.9, w: 0.07, h: 1.15, fill: { color: C.teal } }); |
| s.addText([ |
| { text: "Virtual Cell", options: { bold: true, fontSize: 13, color: C.teal, breakLine: true } }, |
| { text: "AI model simulating real cell behavior: given genotype, environment, perturbation \u2192 predict molecular state changes. Perturbation prediction is its most critical subtask.", options: { fontSize: 10.5, color: C.textMid } }, |
| ], { x: 0.75, y: 0.95, w: 3.8, h: 1.05, valign: "top", fontFace: "Calibri", margin: 0 }); |
|
|
| |
| const types = [ |
| { title: "Drug Perturbation", desc: "Small molecules / drugs (L1000/LINCS)", color: C.accent1 }, |
| { title: "Cytokine Perturbation", desc: "Cytokines (IL-6, TNF-a, IFN-g) signaling", color: C.accent3 }, |
| { title: "Genetic Perturbation", desc: "CRISPR KO / CRISPRa OE / RNAi KD", color: C.accent2 }, |
| ]; |
| const cardX = 5.0, cardW = 4.5, cardH = 0.7; |
| types.forEach((t, i) => { |
| const yy = 0.9 + i * (cardH + 0.12); |
| s.addShape(pres.shapes.RECTANGLE, { x: cardX, y: yy, w: cardW, h: cardH, fill: { color: C.white }, shadow: cardShadow() }); |
| s.addShape(pres.shapes.RECTANGLE, { x: cardX, y: yy, w: 0.07, h: cardH, fill: { color: t.color } }); |
| s.addText(t.title, { |
| x: cardX + 0.2, y: yy + 0.05, w: 4.0, h: 0.28, |
| fontSize: 11.5, fontFace: "Calibri", bold: true, color: C.textDark, margin: 0, |
| }); |
| s.addText(t.desc, { |
| x: cardX + 0.2, y: yy + 0.35, w: 4.0, h: 0.3, |
| fontSize: 9.5, fontFace: "Calibri", color: C.textMid, margin: 0, |
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| }); |
|
|
| |
| s.addShape(pres.shapes.RECTANGLE, { x: 0.5, y: 3.4, w: 9.0, h: 0.5, fill: { color: C.navy } }); |
| s.addText("This work: genetic perturbation (Perturb-seq) = CRISPR perturbation + scRNA-seq readout", { |
| x: 0.7, y: 3.42, w: 8.6, h: 0.46, |
| fontSize: 11.5, fontFace: "Calibri", color: C.white, bold: true, margin: 0, valign: "middle", |
| }); |
|
|
| |
| s.addText([ |
| { text: "Task: ", options: { bold: true, color: C.teal, fontSize: 13 } }, |
| { text: "x_ctrl + perturbation ID \u2192 predict x_pert (x \u2208 R^G, G \u2248 5000 HVG)", options: { color: C.textDark, fontSize: 12, fontFace: "Consolas" } }, |
| ], { x: 0.5, y: 4.05, w: 9.0, h: 0.35, fontFace: "Calibri", margin: 0 }); |
|
|
| |
| s.addText([ |
| { text: "Drug screening acceleration | Combinatorial explosion: N genes \u2192 N(N-1)/2 combos | ", options: { fontSize: 10, color: C.textMid, breakLine: false } }, |
| { text: "No paired data (destructive measurement)", options: { fontSize: 10, color: C.coral, bold: true } }, |
| ], { x: 0.5, y: 4.45, w: 9.0, h: 0.35, fontFace: "Calibri", margin: 0 }); |
| } |
|
|
| |
| |
| |
| slideNum++; |
| addDividerSlide("2. Existing Methods", "And their common blind spot", slideNum); |
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| |
| |
| |
| slideNum++; |
| { |
| const s = addContentSlide("Existing Methods: Overview", slideNum); |
|
|
| const methods = [ |
| { name: "Additive Shift", cat: "Baseline", approach: "Mean shift: x = x_ctrl + delta_mean", issue: "Ignores cell heterogeneity" }, |
| { name: "scGPT", cat: "Foundation Model", approach: "Masked token completion (fine-tune)", issue: "Encodes absolute state, not change" }, |
| { name: "Geneformer", cat: "Foundation Model", approach: "In-silico: delete gene token", issue: "Heuristic, no learned dynamics" }, |
| { name: "CPA", cat: "Dedicated Model", approach: "VAE: basal + perturbation (additive)", issue: "Linear additivity too strong" }, |
| { name: "GEARS", cat: "Dedicated Model", approach: "GNN on GO graph + cross-attention", issue: "Static prior graph, deterministic" }, |
| { name: "STATE", cat: "Dedicated Model", approach: "Stacked attention on expression", issue: "Deterministic, no GRN modeling" }, |
| { name: "CellFlow", cat: "Flow Matching", approach: "FM + pretrained embedding cond.", issue: "Embedding = absolute state" }, |
| { name: "scDFM", cat: "Flow Matching", approach: "Conditional FM + DiffPerceiver", issue: "No GRN understanding" }, |
| ]; |
|
|
| const hY = 0.85; |
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| { x: 2.0, w: 1.5, label: "Category" }, |
| { x: 3.5, w: 3.2, label: "Approach" }, |
| { x: 6.7, w: 2.8, label: "Key Limitation" }, |
| ]; |
|
|
| |
| s.addShape(pres.shapes.RECTANGLE, { x: 0.5, y: hY, w: 9.0, h: 0.35, fill: { color: C.teal } }); |
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| fontSize: 10, fontFace: "Calibri", bold: true, color: C.white, valign: "middle", margin: 0, |
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| }); |
|
|
| |
| const rowH = 0.37; |
| methods.forEach((m, i) => { |
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|
|
| |
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| s.addText([ |
| { text: "Common blind spot: ", options: { bold: true, color: C.gold, fontSize: 13 } }, |
| { text: "Perturbation \u2192 [black box] \u2192 Expression change", options: { color: C.white, fontSize: 13, breakLine: true } }, |
| { text: "No method explicitly models: Perturbation \u2192 GRN rewiring \u2192 Expression change", options: { color: C.subtitleOnDark, fontSize: 11 } }, |
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| } |
|
|
| |
| |
| |
| slideNum++; |
| addDividerSlide("3. Motivation", "Why GRN + Flow Matching?", slideNum); |
|
|
| |
| |
| |
| slideNum++; |
| { |
| const s = addContentSlide("Motivation 1: Flow Matching for Unpaired Data", slideNum); |
|
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| |
| s.addShape(pres.shapes.RECTANGLE, { x: 0.5, y: 0.9, w: 4.2, h: 1.8, fill: { color: C.white }, shadow: cardShadow() }); |
| s.addShape(pres.shapes.RECTANGLE, { x: 0.5, y: 0.9, w: 0.07, h: 1.8, fill: { color: C.coral } }); |
| s.addText([ |
| { text: "The Pairing Problem", options: { bold: true, fontSize: 13, color: C.coral, breakLine: true } }, |
| { text: "", options: { breakLine: true, fontSize: 5 } }, |
| { text: "Perturbation is destructive:", options: { fontSize: 11, color: C.textDark, breakLine: true } }, |
| { text: "One cell measured ONCE only", options: { fontSize: 11, color: C.textDark, breakLine: true } }, |
| { text: "No (x_ctrl, x_pert) pairs available", options: { fontSize: 11, color: C.coral, bold: true, breakLine: true } }, |
| { text: "", options: { breakLine: true, fontSize: 5 } }, |
| { text: "Mean matching \u2192 loses heterogeneity", options: { bullet: true, fontSize: 10, color: C.textMid, breakLine: true } }, |
| { text: "Autoencoder \u2192 limited reconstruction", options: { bullet: true, fontSize: 10, color: C.textMid } }, |
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|
|
| |
| s.addShape(pres.shapes.RECTANGLE, { x: 5.0, y: 0.9, w: 4.5, h: 1.8, fill: { color: C.white }, shadow: cardShadow() }); |
| s.addShape(pres.shapes.RECTANGLE, { x: 5.0, y: 0.9, w: 0.07, h: 1.8, fill: { color: C.accent3 } }); |
| s.addText([ |
| { text: "Flow Matching Solution", options: { bold: true, fontSize: 13, color: C.accent3, breakLine: true } }, |
| { text: "", options: { breakLine: true, fontSize: 5 } }, |
| { text: "Learn probabilistic transport mapping\nbetween distributions (not individual cells)", options: { fontSize: 11, color: C.textDark, breakLine: true } }, |
| { text: "", options: { breakLine: true, fontSize: 5 } }, |
| { text: "Only needs population-level distributions", options: { bullet: true, fontSize: 10, color: C.textMid, breakLine: true } }, |
| { text: "Conditional OT for efficient pairing", options: { bullet: true, fontSize: 10, color: C.textMid, breakLine: true } }, |
| { text: "Generative output = uncertainty estimation", options: { bullet: true, fontSize: 10, color: C.textMid } }, |
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|
|
| |
| s.addShape(pres.shapes.RECTANGLE, { x: 0.5, y: 3.0, w: 9.0, h: 1.6, fill: { color: C.white }, shadow: cardShadow() }); |
|
|
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| s.addText("noise x\u2080", { x: 1.2, y: 3.25, w: 1.8, h: 1.1, fontSize: 12, fontFace: "Calibri", color: C.coral, align: "center", valign: "middle", bold: true, margin: 0 }); |
|
|
| s.addText("v\u03B8( x, t, ctrl, pert )", { |
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| fontSize: 14, fontFace: "Consolas", color: C.teal, align: "center", valign: "middle", bold: true, margin: 0, |
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| s.addText("learned velocity field (ODE)", { |
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| fontSize: 9, fontFace: "Calibri", color: C.textMid, align: "center", margin: 0, |
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|
|
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| } |
|
|
| |
| |
| |
| slideNum++; |
| { |
| const s = addContentSlide("Motivation 2: Perturbation Propagates via GRN", slideNum); |
|
|
| |
| s.addShape(pres.shapes.RECTANGLE, { x: 0.5, y: 0.9, w: 5.5, h: 2.8, fill: { color: C.white }, shadow: cardShadow() }); |
|
|
| const steps = [ |
| { text: "CRISPR knock-out Gene A", color: C.coral, bold: true }, |
| { text: "Gene A expression --> 0", color: C.coral, bold: false }, |
| { text: "Direct targets B, C, D change (1st order)", color: C.accent2, bold: false }, |
| { text: "B->E,F C->G,H D->I ... (cascade)", color: C.accent2, bold: false }, |
| { text: "Thousands of genes ultimately affected", color: C.teal, bold: true }, |
| ]; |
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| const yy = 1.05 + i * 0.45; |
| s.addText((i > 0 ? " | " : " ") + st.text, { |
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| }); |
| }); |
|
|
| s.addText("This cascade path = Gene Regulatory Network (GRN)", { |
| x: 0.8, y: 3.3, w: 5.0, h: 0.3, |
| fontSize: 11, fontFace: "Calibri", color: C.navy, bold: true, italic: true, margin: 0, |
| }); |
|
|
| |
| s.addShape(pres.shapes.RECTANGLE, { x: 6.3, y: 0.9, w: 3.2, h: 1.2, fill: { color: "FEF3C7" }, shadow: cardShadow() }); |
| s.addText([ |
| { text: "Existing Methods", options: { bold: true, fontSize: 12, color: C.textDark, breakLine: true } }, |
| { text: "", options: { breakLine: true, fontSize: 4 } }, |
| { text: "Pert -> [black box] -> Expr", options: { fontSize: 11, fontFace: "Consolas", color: C.coral, breakLine: true } }, |
| { text: "End-to-end, no GRN understanding", options: { fontSize: 10, color: C.textMid } }, |
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|
|
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| s.addText([ |
| { text: "Our Approach", options: { bold: true, fontSize: 12, color: C.textDark, breakLine: true } }, |
| { text: "", options: { breakLine: true, fontSize: 4 } }, |
| { text: "Pert -> GRN change -> Expr", options: { fontSize: 11, fontFace: "Consolas", color: C.accent3, breakLine: true } }, |
| { text: "", options: { breakLine: true, fontSize: 4 } }, |
| { text: "Explicitly model how perturbation rewires the regulatory network, then predict expression", options: { fontSize: 10, color: C.textDark } }, |
| ], { x: 6.5, y: 2.35, w: 2.9, h: 1.3, fontFace: "Calibri", valign: "top", margin: 0 }); |
|
|
| |
| s.addShape(pres.shapes.RECTANGLE, { x: 0.5, y: 4.1, w: 9.0, h: 0.5, fill: { color: C.navy } }); |
| s.addText("Understanding GRN changes is a prerequisite for accurate expression prediction", { |
| x: 0.7, y: 4.12, w: 8.6, h: 0.46, |
| fontSize: 12, fontFace: "Calibri", color: C.gold, bold: true, margin: 0, valign: "middle", |
| }); |
| } |
|
|
| |
| |
| |
| slideNum++; |
| { |
| const s = addContentSlide("Motivation 3: scGPT Attention = Data-Driven GRN", slideNum); |
|
|
| |
| s.addShape(pres.shapes.RECTANGLE, { x: 0.5, y: 0.9, w: 4.5, h: 2.1, fill: { color: C.white }, shadow: cardShadow() }); |
| s.addText([ |
| { text: "scGPT Transformer Attention", options: { bold: true, fontSize: 13, color: C.teal, breakLine: true } }, |
| { text: "", options: { breakLine: true, fontSize: 5 } }, |
| { text: "attn[i][j] high -> gene j influences gene i", options: { fontSize: 11, fontFace: "Consolas", color: C.textDark, breakLine: true } }, |
| { text: "", options: { breakLine: true, fontSize: 5 } }, |
| { text: "= Context-dependent, data-driven GRN", options: { fontSize: 12, color: C.navy, bold: true, breakLine: true } }, |
| { text: "", options: { breakLine: true, fontSize: 5 } }, |
| { text: "vs static GO graph:", options: { bold: true, fontSize: 10, color: C.textMid, breakLine: true } }, |
| { text: "Changes with cell state (context-aware)", options: { bullet: true, fontSize: 10, color: C.textMid, breakLine: true } }, |
| { text: "Learned from massive scRNA-seq data", options: { bullet: true, fontSize: 10, color: C.textMid, breakLine: true } }, |
| { text: "Captures non-linear regulatory logic", options: { bullet: true, fontSize: 10, color: C.textMid } }, |
| ], { x: 0.7, y: 0.95, w: 4.1, h: 2.0, fontFace: "Calibri", valign: "top", margin: 0 }); |
|
|
| |
| s.addShape(pres.shapes.RECTANGLE, { x: 5.3, y: 0.9, w: 4.2, h: 2.1, fill: { color: C.white }, shadow: cardShadow() }); |
| s.addShape(pres.shapes.RECTANGLE, { x: 5.3, y: 0.9, w: 0.07, h: 2.1, fill: { color: C.gold } }); |
| s.addText([ |
| { text: "Attention-Delta", options: { bold: true, fontSize: 13, color: C.accent2, breakLine: true } }, |
| { text: "", options: { breakLine: true, fontSize: 5 } }, |
| { text: "Same frozen scGPT, two inputs:", options: { fontSize: 11, color: C.textDark, breakLine: true } }, |
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| { text: "attn_pert = scGPT(x_pert)", options: { fontSize: 10.5, fontFace: "Consolas", color: C.coral, breakLine: true } }, |
| { text: "", options: { breakLine: true, fontSize: 4 } }, |
| { text: "delta_attn = attn_pert - attn_ctrl", options: { fontSize: 11, fontFace: "Consolas", color: C.navy, bold: true, breakLine: true } }, |
| { text: "", options: { breakLine: true, fontSize: 4 } }, |
| { text: "Directly captures how perturbation\nrewires gene regulatory relationships", options: { fontSize: 10, color: C.textDark } }, |
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| { text: "GRN Change Features:", options: { bold: true, fontSize: 14, color: C.gold, breakLine: true } }, |
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| { text: "z = delta_attn x gene_embeddings", options: { fontSize: 17, fontFace: "Consolas", color: C.white, breakLine: true } }, |
| { text: " (G x G) (G x 512) --> (G x 512)", options: { fontSize: 11, fontFace: "Consolas", color: C.subtitleOnDark } }, |
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| addDividerSlide("4. Our Method", "GRN-Guided Cascaded Flow Matching", slideNum); |
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| slideNum++; |
| { |
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| { text: "Stage 1: GRN Latent Flow", options: { bold: true, fontSize: 13, color: C.accent2, breakLine: true } }, |
| { text: "", options: { breakLine: true, fontSize: 6 } }, |
| { text: "noise ==(ODE)==> GRN features", options: { fontSize: 12, fontFace: "Consolas", color: C.textDark, breakLine: true } }, |
| { text: "", options: { breakLine: true, fontSize: 6 } }, |
| { text: "\"Understand how gene regulation\n changes under perturbation\"", options: { fontSize: 11, color: C.accent2, italic: true, breakLine: true } }, |
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| { text: "", options: { breakLine: true, fontSize: 6 } }, |
| { text: "noise ==(ODE)==> expression", options: { fontSize: 12, fontFace: "Consolas", color: C.textDark, breakLine: true } }, |
| { text: "", options: { breakLine: true, fontSize: 6 } }, |
| { text: "\"Based on GRN understanding,\n predict gene expression changes\"", options: { fontSize: 11, color: C.accent1, italic: true, breakLine: true } }, |
| { text: "", options: { breakLine: true, fontSize: 6 } }, |
| { text: "t_expr: 0 -> 1", options: { fontSize: 10, fontFace: "Consolas", color: C.textMid, breakLine: true } }, |
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| s.addText("Bio intuition: First understand HOW regulation changes, THEN predict WHAT expression changes", { |
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| { text: "Probabilistic switching (not simultaneous)", options: { fontSize: 12, color: C.textDark, breakLine: true } }, |
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| { |
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| { text: "Shared Backbone", options: { bold: true, fontSize: 13, color: C.white, breakLine: true } }, |
| { text: "", options: { breakLine: true, fontSize: 3 } }, |
| { text: "DiffPerceiverBlock x 4", options: { fontSize: 11, color: C.mint, breakLine: true } }, |
| { text: "(GeneadaLN + Adapter + DiffAttn)", options: { fontSize: 9, color: C.mint, breakLine: true } }, |
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| s.addText("c = t_expr + t_latent + pert_emb", { |
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| slideNum++; |
| addDividerSlide("5. Current Challenges", "And proposed solutions", slideNum); |
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| { |
| const s = addContentSlide("Challenges & Solutions", slideNum); |
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| { text: "Challenge 1: Noise in Attention", options: { bold: true, fontSize: 12, color: C.coral, breakLine: true } }, |
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| { text: "Attention: 5000x5000 = 25M non-zero values", options: { fontSize: 10, color: C.textDark, breakLine: true } }, |
| { text: "Real GRN: ~20-50 regulators per gene", options: { fontSize: 10, color: C.textDark, breakLine: true } }, |
| { text: "99%+ values are noise!", options: { fontSize: 11, color: C.coral, bold: true, breakLine: true } }, |
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| { text: "Evidence: latent loss ~ 1.12", options: { fontSize: 10, color: C.textMid, breakLine: true } }, |
| { text: " >> expr loss ~ 0.019", options: { fontSize: 10, color: C.textMid } }, |
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| { text: "Solution: Sparse Top-K", options: { bold: true, fontSize: 12, color: C.accent3, breakLine: true } }, |
| { text: "", options: { breakLine: true, fontSize: 4 } }, |
| { text: "Per gene: keep only K=30 largest |delta|", options: { fontSize: 10, color: C.textDark, breakLine: true } }, |
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| { text: "Not architectural improvement -- biological mechanism-driven modeling", options: { color: C.white, fontSize: 12, breakLine: true } }, |
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