Martelli, E. | Search bioRxiv

bioRxiv2026

REBEL, Reproducible Environment Builder for Explicit Library resolution

BackgroundAchieving FAIR-compliant computational research in bioinformatics is systematically undermined by two compounding challenges that existing tools leave unresolved: long-term reproducibility and accessibility. Standard package managers re-download dependencies from live repositories at every build, making environments vulnerable to library disappearance and version drift, and pinning a package version does not pin the versions of its transitive dependencies, causing divergences between builds performed at different points in time. Compounding this, packages from repositories such as CRAN, Bioconductor, and PyPI frequently omit critical system-level dependencies from their installation metadata, leaving users to manually discover which underlying library is missing or which version is required. Beyond these technical failures, constructing a truly reproducible environment demands expertise in containerization making reproducibility in practice a privilege and not a standard. FindingsWe present REBEL (Reproducible Environment Builder for Explicit Library Resolution), a framework that addresses both challenges through three dependency inference heuristics: (i) Deep Inspection of source code, (ii) Fuzzy Matching against a manually curated knowledge base, and (iii) Conservative Dependency Locking. The resolved dependency stack is then archived into a self-contained local store, enabling offline and deterministic rebuilds at any future time. We compared the installation of 1,000 randomly sampled CRAN packages in isolated Docker containers versus the standard package manager and REBEL resolved 149 of 328 standard installation failures (45.4%). Moreover through its DockerBuilder component, REBEL further generates fully reproducible Docker images from a plain text requirements file, making deterministic environment construction accessible without expertise in containerization. ConclusionsREBEL provides a practical foundation for FAIR-compliant, long-term reproducible bioinformatics analyses, making deterministic environment construction accessible to researchers regardless of their technical background. REBEL is freely available at https://github.com/Rebel-Project-Core

bioinformatics↗

bioRxiv2025

Long-term mavacamten exposure reduces force and sarcomere density in a hiPSC model of hypertrophic cardiomyopathy

BackgroundMavacamten, a first-in-class allosteric myosin inhibitor, has demonstrated efficacy and safety in obstructive hypertrophic cardiomyopathy (oHCM), notably reducing symptoms, left ventricular outflow obstruction, and wall thickness over 30 weeks. We recently reported that the MYBPC3:c.772G>A variant causes HCM through cMyBP-C haploinsufficiency, leading to accelerated sarcomere kinetics and higher energy consumption in patient myocardium and hiPSC- derived cardiomyocytes (hiPSC-CMs). These effects are counterbalanced by prolonged action potentials and slower Ca{superscript 2} transients, which preserve twitch duration but may increase arrhythmic risk. Mavacamten may reduce myocardial energetic defects in HCM. ObjectivesTo investigate the long-term effects of Mavacamten on sarcomere structure, contractility, and transcriptional remodeling using patient-specific and CRISPR-corrected isogenic hiPSC-derived cardiomyocyte models of HCM. MethodsHiPSC-CMs and engineered heart tissues (EHTs) derived from a MYBPC3:c.772G>A patient and its CRISPR-corrected line were first exposed to increasing concentrations of Mavacamten to assess acute dose-response relationships and determine IC50 values. Based on these data, chronic treatments (0.3- 0.75 M for 20 days) were performed mechanical, structural, electrophysiological, and transcriptomic adaptations. ResultsAcute exposure produced a rapid and fully reversible reduction in active force, while chronic treatment for 20 days induced a sustained decrease in contractility with incomplete recovery after 4 days of washout, indicating a two-phase mechanism of action. Long-term force reduction was paralleled by decreased cell area and sarcomere density, indicating that structural disassembly contributes to sustained functional depression and re-assembly after washout. Electrophysiological analysis confirmed the specific alterations of the MYBPC3:c.772G>A mutation previously observed, with no detectable effects following treatment with Mavacamten. In addition, transcriptome analysis was used to study the molecular mechanisms underlying the long-term effect. ConclusionsMavacamten induces a biphasic, persistent-to-reversible, reduction of sarcomeric force associated with structural remodeling, providing mechanistic insight into its capacity to promote favorable cardiac remodeling in oHCM.

physiology↗