Development and validation of a novel and robust blood small nuclear RNA signature in diagnosing autism spectrum disorder

Reliable molecular signatures are needed to improve the early and accurate diagnosis of autism spectrum disorder (ASD), and indicate physicians to provide timely intervention. This study aimed to identify a robust blood small nuclear RNA (snRNA) signature in diagnosing ASD. 186 blood samples in the microarray dataset were randomly divided into the training set (n = 112) and validation set (n = 72). Then, the microarray probe expression profiles were re-annotated into the expression profiles of 1253 snRNAs though probe sequence mapping. In the training set, least absolute shrinkage and selection operator (LASSO) penalized generalized linear model was adopted to identify the 9-snRNA signature (RNU1-16P, RNU6-1031P, RNU6-258P, RNU6-335P, RNU6-485P, RNU6-549P, RNU6-98P, RNU6ATAC26P, and RNVU1-15), and a diagnostic score was calculated for each sample according to the snRNA expression levels and the model coefficients. The score demonstrated a good diagnostic ability for ASD in the training set (area under receiver operating characteristic curve (AUC) = 0.90), validation set (AUC = 0.87), and the overall (AUC = 0.88). Moreover, the blood samples of 23 ASD patients and 23 age- and gender-matched controls were collected as the external validation set, in which the signature also showed a good diagnostic ability for ASD (AUC = 0.88). In subgroup analysis, the signature was robust when considering the confounders of gender, age, and disease subtypes, and displayed a significantly better performance among the female and younger cases (P = .039; P = .002). In comparison with a 55-gene signature deriving from the same dataset, the snRNA signature showed a better diagnostic ability (AUC: 0.88 vs 0.80, P = .049). In conclusion, this study identified a novel and robust blood snRNA signature in diagnosing ASD, which might help improve the diagnostic accuracy for ASD in clinical practice. Nevertheless, a large-scale prospective study was needed to validate our results.