PNAS

Molecular assembly as a universal biosignature measurable by mass spectrometry

2026-08-10

Detecting life beyond Earth requires biosignatures that do not depend on the chemistry of known organisms. Molecular assembly (MA), derived from Assembly Theory, quantifies how difficult it is to build a molecule from basic building blocks, linking complexity directly to selection and evolution. Here, we show that MA can serve as a universal biosignature that is both interpretable and experimentally measurable. Unlike information-theoretic measures, MA can be inferred directly from mass spectrometry data without structural elucidation. We demonstrate this using a machine learning model trained on standardized single-stage (MS 1 ) spectra, which predicts MA with three-fold lower error than baseline methods. Simulated multistage (MS n ) data reveal that small instrumental variations can double prediction error, highlighting the importance of calibration. These findings establish molecular assembly as a physically grounded, quantifiable biosignature measurable by mass spectrometry whose interpretation depends on careful control of instrumental effects, offering a scalable route to life detection on future planetary missions.

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DOI https://doi.org/10.1073/pnas.2619198123