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PreprintCC BYbioRxiv

Scalable and semi-automated Boolean network inference from multi-condition single-cell transcriptomes with scBOLT

Abstract

Predictive logical models have made substantial contributions to biomedical research by facilitating the identification of regulatory mechanisms driving biological processes. Yet, their construction remains a major bottleneck, as it typically relies on extensive prior knowledge at the genome scale. The emergence of high-throughput omics technologies has opened new opportunities for data-driven logical model construction by providing high-resolution observations of biological states. In parallel, formal constraint-based approaches have emerged, reformulating executable model inference as a constraint-satisfaction problem. However, transforming omics observations into biologically meaningful Boolean state abstractions and dynamical constraints suitable for logical synthesis engines remains challenging, particularly for poorly understood biological systems and multi-condition experimental settings. To address these challenges, we introduce scBOLT, a semi-automated framework for Boolean constraint engineering and logical model inference from multi-condition single-cell transcriptomes. Beyond these methodological contributions, scBOLT substantially improves computational tractability, enabling the inference of Boolean networks comprising several hundred components within practical runtimes.

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BibTeX
@misc{roncalli2026scalable,
  title = {{Scalable and semi-automated Boolean network inference from multi-condition single-cell transcriptomes with scBOLT}},
  author = {T. Roncalli and E. Remy and L. Pauleve},
  howpublished = {bioRxiv},
  year = {2026},
  month = oct,
  doi = {10.64898/2026.10.02.756175},
  url = {https://www.biorxiv.org/content/10.64898/2026.10.02.756175v1},
  note = {CC BY},
}
RIS
TY  - UNPB
TI  - Scalable and semi-automated Boolean network inference from multi-condition single-cell transcriptomes with scBOLT
AU  - T. Roncalli
AU  - E. Remy
AU  - L. Pauleve
PY  - 2026
DA  - 2026/10/02
PB  - bioRxiv
DO  - 10.64898/2026.10.02.756175
UR  - https://www.biorxiv.org/content/10.64898/2026.10.02.756175v1
AB  - Predictive logical models have made substantial contributions to biomedical research by facilitating the identification of regulatory mechanisms driving biological processes. Yet, their construction remains a major bottleneck, as it typically relies on extensive prior knowledge at the genome scale. The emergence of high-throughput omics technologies has opened new opportunities for data-driven logical model construction by providing high-resolution observations of biological states. In parallel, formal constraint-based approaches have emerged, reformulating executable model inference as a constraint-satisfaction problem. However, transforming omics observations into biologically meaningful Boolean state abstractions and dynamical constraints suitable for logical synthesis engines remains challenging, particularly for poorly understood biological systems and multi-condition experimental settings. To address these challenges, we introduce scBOLT, a semi-automated framework for Boolean constraint engineering and logical model inference from multi-condition single-cell transcriptomes. Beyond these methodological contributions, scBOLT substantially improves computational tractability, enabling the inference of Boolean networks comprising several hundred components within practical runtimes.
ER  -