Challenges in biomarker discovery research

The pattern, severity, and location of white matter injury after premature birth are highly associated with adverse neurodevelopmental outcomes. 1 There has been progress in identifying potential therapeutic targets, 2 , 3 However, unfortunately, it is very difficult to identify affected infants in a timely manner for potential controlled trials, in part because clinical signs are often subtle, their baseline muscle tone is lower than at term, and even when seizures occur, they typically aren’t manifested clinically. 4 , 5 Magnetic resonance imaging is accurate, but it is expensive, not always available, and is usually delayed until term-equivalent age, and so can underestimate the burden of injury. 6 Because of these issues, the trials of neuroprotection so far have recruited all infants within a gestational age range. 7 , 8 Thus, there is a critical unmet need for diagnostic biomarkers of early brain injury. Circulating microRNAs (miRNAs) in the blood reflect ongoing injury processes and therefore represent a promising avenue for early detection and longitudinal monitoring of brain injury, as repeated samples can be easily obtained. 9 Next-generation sequencing (NGS) is considered the gold standard for discovering novel miRNA biomarkers. However, the need for large sample volumes and potential lack of sensitivity for low-abundance RNAs limit its potential.