Archive 4 checkpoints (1-4)

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@@ -125,3 +125,4 @@ paper-releases/pbisc-diffusion/updates/20261012T090327Z-uniform-manuscript-margi
 paper-releases/pbisc-diffusion/updates/20261012T090327Z-uniform-manuscript-margins/diffusion/dataset/server_1/manuscript/supplementary.pdf filter=lfs diff=lfs merge=lfs -text
 paper-releases/pbisc-diffusion/updates/20261012T091446Z-frontmatter-word-export/diffusion/dataset/server_1/manuscript/archive/word_exports/20261012T091054Z/preview/PBISC-Diffusion_Title_Abstract_Introduction_20261012.pdf filter=lfs diff=lfs merge=lfs -text
 paper-releases/pbisc-diffusion/updates/20261012T104812Z-jh-introduction-edit/diffusion/dataset/server_1/manuscript/main.pdf filter=lfs diff=lfs merge=lfs -text
+paper-releases/pbisc-diffusion/updates/20261012T121201Z-abstract-pretraining-lora/diffusion/dataset/server_1/manuscript/main.pdf filter=lfs diff=lfs merge=lfs -text

paper-releases/pbisc-diffusion/updates/20261012T121201Z-abstract-pretraining-lora/diffusion/dataset/server_1/manuscript/editorial/abstract_pretraining_lora_20261012.json

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+  "date": "2026-10-12",
+  "source": "User-approved replacement passage, writing block 84162.",
+  "approved_passage": "Existing bulk-to-single-cell approaches can be limited by the cellular diversity represented in selected references and by differences between pseudobulk and measured bulk RNA-seq. Here we introduce PBISC, a bulk-conditioned diffusion model that combines pretraining on over 33 million single cells with low-rank adaptation (LoRA) using paired bulk and single-cell data from just five donors. The adapted model generates single-cell profiles for the remaining cohort from bulk measurements alone.",
+  "replaced_passage": "Generative approaches infer individual cells using various machine learning methods but are constrained by small reference cohorts and there are mismatch between pseudobulk and measured bulk RNA-seq. Here we introduce PBISC, a diffusion model pretrained on over 33 million single cells for generating single-cell RNA profiles conditioned on a sample's bulk transcriptome. Using paired bulk and single-cell data from minimum five donors, the model adapted to the target bulk sequencing protocol and generates single-cell profiles for the remaining cohort.",
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+  "scope": "Only the three approved Abstract sentences are replaced; pretraining and five-donor LoRA adaptation are introduced together.",
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paper-releases/pbisc-diffusion/updates/20261012T121201Z-abstract-pretraining-lora/diffusion/dataset/server_1/manuscript/main.pdf

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paper-releases/pbisc-diffusion/updates/20261012T121201Z-abstract-pretraining-lora/diffusion/dataset/server_1/manuscript/sections/abstract.tex

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+Bulk RNA sequencing offers cost-effective, sensitive transcriptome profiling but averages expression across cells, obscuring cellular heterogeneity. Deconvolution methods estimate cell-type composition and expression from the bulk dataset but do not resolve variation within cell types. Existing bulk-to-single-cell approaches can be limited by the cellular diversity represented in selected references and by differences between pseudobulk and measured bulk RNA-seq. Here we introduce PBISC, a bulk-conditioned diffusion model that combines pretraining on over 33 million single cells with low-rank adaptation (LoRA) using paired bulk and single-cell data from just five donors. The adapted model generates single-cell profiles for the remaining cohort from bulk measurements alone. By repeated sampling from independent Gaussian noise, we were able to produce a synthetic cell population representing the sample's cellular heterogeneity. Pre-annotated cell types were not used for either training or generation, allowing PBISC to generate rare cell populations without defining them as separate categories in advance. Furthermore, PBISC showed improved preservation of disease-associated expression changes relative to comparator methods in most evaluated settings. Together, these results support extending analyses at single-cell resolution to large cohorts profiled by bulk RNA-seq.