Blood biomarker discovery for autism spectrum disorder: A proteomic analysis

• Published in: PloS one 2024-12, Vol.19 (12), p.e0302951
• Main Authors: Hewitson, Laura, Mathews, Jeremy A, Devlin, Morgan, Schutte, Claire, Lee, Jeon, German, Dwight C
• Format: Article
• Language: English
• Subjects: Algorithms; Autism; Autism Spectrum Disorder - blood; Autism Spectrum Disorder - diagnosis; Behavior; Biology and Life Sciences; Biomarkers; Biomarkers - blood; Blood; Blood proteins; Case-Control Studies; Child; Child, Preschool; Children & youth; Correlation analysis; Discovery and exploration; Health care; Heterogeneity; Humans; Machine learning; Male; Medical research; Medicine and Health Sciences; Medicine, Experimental; Neurodevelopmental disorders; People and Places; Proteins; Proteomics; Proteomics - methods; Review boards; Serum proteins; Social aspects; Social behavior; Social Sciences
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0302951

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social communication and social interaction and restricted, repetitive patterns of behavior, interests, or activities. Given the lack of specific pharmacological therapy for ASD and the clinical heterogeneity of the disorder, current biomarker research efforts are geared mainly toward identifying markers for determining ASD risk or for assisting with a diagnosis. A wide range of putative biological markers for ASD are currently being investigated. Proteomic analyses indicate that the levels of many proteins in plasma/serum are altered in ASD, suggesting that a panel of proteins may provide a blood biomarker for ASD. Serum samples from 76 boys with ASD and 78 typically developing (TD) boys, 2-10 years of age, were analyzed to identify possible early biological markers for ASD. Proteomic analysis of serum was performed using SomaLogic's SOMAScanTM assay 1.3K platform. A total of 1,125 proteins were analyzed. There were 86 downregulated proteins and 52 upregulated proteins in ASD (FDR < 0.05). Combining three different algorithms, we found a panel of 12 proteins that identified ASD with an area under the curve (AUC) = 0.8790±0.0572, with specificity and sensitivity of 0.8530±0.1076 and 0.8324±0.1137, respectively. All 12 proteins were significantly different in ASD compared with TD boys, and 4 were significantly correlated with ASD severity as measured by ADOS total scores. Using machine learning methods, a panel of serum proteins was identified that may be useful as a blood biomarker for ASD in boys. Further verification of the protein biomarker panel with independent test sets is warranted.