Description

To determine the sample size needed to derive a signature matrix to identify novel biomarkers in sepsis, investigators performed a mathematical modeling exercise of the lower limits of sensitivity of this liquid biopsy approach. The detection limit of cell-free nucleic acid analysis is determined in part by the number of independent transcripts or "reporters" that are interrogated. Using an established and independently validated binomial model that was previously applied to the prediction of circulating tumor nucleic acid detection limits, investigators estimated the probability of cell-free nucleic acid detection in sepsis patients based on the number of unique tissue-specific reporters (i.e., hepatic transcripts that may reflect disease severity). This yields a result of n=18 per group to achieve 0.90 power at alpha=0.05. The investigators will thus plan to analyze data from n=18 per cell/tissue type to derive the signature matrix for this project.