Urinary Proteome Profiling for Children with Autism Using Data-independent Acquisition Proteomics

Overview

Journal Transl Pediatr

Publisher AME Publishing Company

Specialty Pediatrics

Date 2021 Aug 25

PMID 34430425

Citations 7

Authors

Wenshu Meng

Yuhang Huan

Youhe Gao

Affiliations

Soon will be listed here.

Abstract

Background: Autism is a complex neurodevelopmental disorder. Objective and reliable biomarkers are crucial for the clinical diagnosis of autism. Urine can accumulate early changes of the whole body and is a sensitive source for disease biomarkers.

Methods: The data-independent acquisition (DIA) strategy was used to identify differential proteins in the urinary proteome between autistic and non-autistic children aged 3-7 years. Receiver operating characteristic (ROC) curves were developed to evaluate the diagnostic performance of differential proteins.

Results: A total of 118 differential proteins were identified in the urine between autistic and non-autistic children, of which 18 proteins were reported to be related to autism. Randomized grouping statistical analysis indicated that 91.5% of the differential proteins were reliable. Functional analysis revealed that some differential proteins were associated with axonal guidance signaling, endocannabinoid developing neuron pathway, synaptic long-term depression, agrin interactions at neuromuscular junction, phosphatase and tensin homolog deleted on chromosome 10 (PTEN) signaling and synaptogenesis signaling pathway. The combination of cadherin-related family member 5 (CDHR5) and vacuolar protein sorting-associated protein 4B (VPS4B) showed the best discriminative performance between autistic and non-autistic children with an area under the curve (AUC) value of 0.987.

Conclusions: The urinary proteome could distinguish between autistic children and non-autistic children. This study will provide a promising approach for future biomarker research of neuropsychiatric disorders.

Citing Articles

Urinary Proteome and Exosome Analysis Protocol for the Discovery of Respiratory Diseases Biomarkers.

Martelo-Vidal L, Vazquez-Mera S, Miguens-Suarez P, Bravo-Lopez S, Makrinioti H, Dominguez-Arca V Biomolecules. 2025; 15(1).

PMID: 39858454 PMC: 11762655. DOI: 10.3390/biom15010060.

Biomarkers and pathways in autism spectrum disorder: An individual meta-analysis based on proteomic and metabolomic data.

Xie K, Sun Y, Li X, Yang S, Wang M, Zhang Y Eur Arch Psychiatry Clin Neurosci. 2024; .

PMID: 39361099 DOI: 10.1007/s00406-024-01922-9.

Host-derived protein profiles of human neonatal meconium across gestational ages.

Shitara Y, Konno R, Yoshihara M, Kashima K, Ito A, Mukai T Nat Commun. 2024; 15(1):5543.

PMID: 39019879 PMC: 11255260. DOI: 10.1038/s41467-024-49805-w.

Recent progress in mass spectrometry-based urinary proteomics.

Joshi N, Garapati K, Ghose V, Kandasamy R, Pandey A Clin Proteomics. 2024; 21(1):14.

PMID: 38389064 PMC: 10885485. DOI: 10.1186/s12014-024-09462-z.

Urine proteomic analysis of the rat e-cigarette model.

Liu Y, Shen Z, Zhao C, Gao Y PeerJ. 2023; 11:e16041.

PMID: 37753171 PMC: 10519197. DOI: 10.7717/peerj.16041.

References

Krueger D, Brose N . Evidence for a common endocannabinoid-related pathomechanism in autism spectrum disorders. Neuron. 2013; 78(3):408-10. DOI: 10.1016/j.neuron.2013.04.030. View

McFadden K, Minshew N . Evidence for dysregulation of axonal growth and guidance in the etiology of ASD. Front Hum Neurosci. 2013; 7:671. PMC: 3804918. DOI: 10.3389/fnhum.2013.00671. View

Abraham J, Szoko N, Natowicz M . Proteomic Investigations of Autism Spectrum Disorder: Past Findings, Current Challenges, and Future Prospects. Adv Exp Med Biol. 2019; 1118:235-252. DOI: 10.1007/978-3-030-05542-4_12. View

Lai M, Lombardo M, Baron-Cohen S . Autism. Lancet. 2013; 383(9920):896-910. DOI: 10.1016/S0140-6736(13)61539-1. View

Guang S, Pang N, Deng X, Yang L, He F, Wu L . Synaptopathology Involved in Autism Spectrum Disorder. Front Cell Neurosci. 2019; 12:470. PMC: 6309163. DOI: 10.3389/fncel.2018.00470. View

Watanabe Y, Hirao Y, Kasuga K, Tokutake T, Semizu Y, Kitamura K . Molecular Network Analysis of the Urinary Proteome of Alzheimer's Disease Patients. Dement Geriatr Cogn Dis Extra. 2019; 9(1):53-65. PMC: 6477484. DOI: 10.1159/000496100. View

Shen L, Zhang K, Feng C, Chen Y, Li S, Iqbal J . iTRAQ-Based Proteomic Analysis Reveals Protein Profile in Plasma from Children with Autism. Proteomics Clin Appl. 2017; 12(3):e1700085. DOI: 10.1002/prca.201700085. View

Parikshak N, Swarup V, Belgard T, Irimia M, Ramaswami G, Gandal M . Genome-wide changes in lncRNA, splicing, and regional gene expression patterns in autism. Nature. 2016; 540(7633):423-427. PMC: 7102905. DOI: 10.1038/nature20612. View

Lee S, Sharma M, Sudhof T, Shen J . Synaptic function of nicastrin in hippocampal neurons. Proc Natl Acad Sci U S A. 2014; 111(24):8973-8. PMC: 4066509. DOI: 10.1073/pnas.1408554111. View

10.

Hao X, Guo Z, Sun H, Liu X, Zhang Y, Zhang L . Urinary protein biomarkers for pediatric medulloblastoma. J Proteomics. 2020; 225:103832. DOI: 10.1016/j.jprot.2020.103832. View

11.

Shimamoto C, Ohnishi T, Maekawa M, Watanabe A, Ohba H, Arai R . Functional characterization of FABP3, 5 and 7 gene variants identified in schizophrenia and autism spectrum disorder and mouse behavioral studies. Hum Mol Genet. 2015; 24(8):2409. PMC: 4380078. DOI: 10.1093/hmg/ddv011. View

12.

Chapman N, Nato Jr A, Bernier R, Ankenman K, Sohi H, Munson J . Whole exome sequencing in extended families with autism spectrum disorder implicates four candidate genes. Hum Genet. 2015; 134(10):1055-68. PMC: 4578871. DOI: 10.1007/s00439-015-1585-y. View

13.

Roohi J, Montagna C, Tegay D, Palmer L, DeVincent C, Pomeroy J . Disruption of contactin 4 in three subjects with autism spectrum disorder. J Med Genet. 2008; 46(3):176-82. PMC: 2643049. DOI: 10.1136/jmg.2008.057505. View

14.

Ashwood P . Differential T Cell Levels of Tumor Necrosis Factor Receptor-II in Children With Autism. Front Psychiatry. 2018; 9:543. PMC: 6256095. DOI: 10.3389/fpsyt.2018.00543. View

15.

Hu Z, Yang Y, Zhao Y, Yu H, Ying X, Zhou D . APOE hypermethylation is associated with autism spectrum disorder in a Chinese population. Exp Ther Med. 2018; 15(6):4749-4754. PMC: 5958870. DOI: 10.3892/etm.2018.6069. View

16.

Sener E, Cikili Uytun M, Bayramov K, Zararsiz G, Oztop D, Canatan H . The roles of CC2D1A and HTR1A gene expressions in autism spectrum disorders. Metab Brain Dis. 2016; 31(3):613-9. DOI: 10.1007/s11011-016-9795-0. View

17.

Zamberletti E, Gabaglio M, Parolaro D . The Endocannabinoid System and Autism Spectrum Disorders: Insights from Animal Models. Int J Mol Sci. 2017; 18(9). PMC: 5618565. DOI: 10.3390/ijms18091916. View

18.

Huang D, Sherman B, Lempicki R . Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2009; 4(1):44-57. DOI: 10.1038/nprot.2008.211. View

19.

Mandic-Maravic V, Mitkovic-Voncina M, Pljesa-Ercegovac M, Savic-Radojevic A, Djordjevic M, Pekmezovic T . Autism Spectrum Disorders and Perinatal Complications-Is Oxidative Stress the Connection?. Front Psychiatry. 2019; 10:675. PMC: 6798050. DOI: 10.3389/fpsyt.2019.00675. View

20.

Zhang L, Huang C, Dai Y, Luo Q, Ji Y, Wang K . Symptom improvement in children with autism spectrum disorder following bumetanide administration is associated with decreased GABA/glutamate ratios. Transl Psychiatry. 2020; 10(1):9. PMC: 7026137. DOI: 10.1038/s41398-020-0692-2. View