{
  "abstract": "Understanding genome regulation is limited by the complexity of molecular interactions in living cells. Cell-free systems provide a simplified platform for studying gene expression, but low mRNA levels have prevented RNA-seq. To address this, we develop an active learning workflow combining Bayesian optimization with automated high-throughput experimentation to systematically explore over 1.6 million buffer compositions, experimentally testing 653. We identify a “mRNA-optimized” buffer (20-fold increase in mRNA yield) and a “trade-off” buffer (13-fold increase while maintaining protein production). Using direct RNA-seq, we profile the T7 phage transcriptome in cell-free systems and compare it with a purified T7-RNAP transcription system and phage-infected bacteria. This comparative analysis reveals distinct regulatory layers: the T7-RNAP system captures promoter-strength hierarchies but lacks RNA degradation, whereas cell-free systems provide an accurate estimation of in vivo expression and reveal mRNA maturation sites. This work establishes cell-free transcriptomics as a controlled approach to study genome regulation.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "name": "Léa Wagner"
    },
    {
      "name": "An Hoang"
    },
    {
      "name": "Olivier Rue"
    },
    {
      "name": "Olivier Delumeau"
    },
    {
      "name": "Valentin Loux"
    },
    {
      "name": "Gabin Derache"
    },
    {
      "name": "Jean-Loup Faulon"
    },
    {
      "name": "Matthieu Jules"
    },
    {
      "name": "Olivier Borkowski"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8tbes5abnhjcd.bib",
  "cited_by": 0,
  "doi": "10.1038/s41467-026-74559-y",
  "fulltext_url": null,
  "id": "8tbes5abnhjcd",
  "issns": [
    "2041-1723",
    "2041-1723"
  ],
  "landing_url": "https://hal.inrae.fr/hal-05802646v1",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
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  "pdf_url": "https://hal.inrae.fr/hal-05802646/document",
  "pmcid": null,
  "pmid": null,
  "published": "2026-06-27",
  "publisher": "Nature Publishing Group",
  "ris": "https://research.draconitic.com/paper/8tbes5abnhjcd.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:58Z",
      "native_id": "hal-05802646",
      "source": "hal",
      "url": "https://hal.inrae.fr/hal-05802646v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "hal:2.sdv.bbm.bm",
      "subfield": "molecular-biology"
    },
    {
      "field": "biology",
      "origin": "hal:1.sdv.bibs",
      "subfield": "bioinformatics"
    },
    {
      "field": "biology",
      "origin": "hal:1.sdv.gen",
      "subfield": "genetics-genomics"
    },
    {
      "field": "biology",
      "origin": "hal:1.sdv.mp",
      "subfield": "microbiology"
    },
    {
      "field": "biology",
      "origin": "hal:1.sdv.bio",
      "subfield": "systems-synthetic"
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  ],
  "title": "Active-learning-guided optimization of cell-free systems for genome-wide transcriptomic profiling reveals progressive layers of regulation",
  "title_text": "Active-learning-guided optimization of cell-free systems for genome-wide transcriptomic profiling reveals progressive layers of regulation",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:58Z",
  "url": "https://research.draconitic.com/paper/8tbes5abnhjcd",
  "venue": "Nature Communications",
  "versions": []
}