Small- and wide-angle X-ray scattering (SWAXS) is a powerful technique for investigating the shape and dynamics of biological macromolecules in solution. Despite its growing popularity, the field has lacked robust metrics for quantifying SWAXS data and model precision and accuracy, undermining confidence in results and limiting wider adoption. To address this critical gap, we introduce PRISM (Probabilistic Resolution Inference from SWAXS Measurement), a statistical framework that properly accounts for the statistical properties of the model-data fit to provide quantitative measures that reveal global and local model confidence from SWAXS. Our PRISM framework leverages Shannon Information theory to provide three key advances: (1) accurate quantification of the amount and precision of information in a SWAXS profile that enables objective comparison between data sets; (2) a data quality-aware measure of model-data fit that provides more trustworthy structural assessments; and (3) novel statistical metrics used to quantify global, local (per-atom), and relational structural uncertainty of SWAXS models. Tests across diverse experimental and simulated SWAXS data sets demonstrate that our novel statistical framework is robust, intuitive, and represents an entirely new level of analytical depth and insight for SWAXS-based structural modeling. PRISM is set to establish a new paradigm for SWAXS data and model quality assessment, promoting rigor, reproducibility, and objectivity, and providing a quantitative language for confidence that has been sorely lacking in the field.
Oduro et al. (Sun,) studied this question.