A Combined Proteomics and Metabolomics Profiling to Investigate the Genetic Heterogeneity of Autistic Children

Abstract

Background: Autism spectrum disorder (ASD) has become one of the most common neurological developmental disorders in children. However, the study of ASD diagnostic markers faces signi cant challenges due to the existence of heterogeneity.Methods: In this study, genetic testing was performed on children who were clinically diagnosed with ASD. Children with ASD susceptibility genes and healthy controls were studied. The proteomics of plasma and peripheral blood mononuclear cells (PBMCs) as well as plasma metabolomics were carried out.Results: The results showed that although there was genetic heterogeneity in children with ASD, the differentially expressed proteins (DEPs) in plasma, PBMCs, and differential metabolites in plasma could still effectively distinguish autistic children from controls. The mechanism associated with them focus on several common and previously reported mechanisms of ASD.Limitations: The number of samples carrying risk genes in omics research is limited. In further research, a large sample size is required. A group of children who have been diagnosed with ASD but have not been detected to carry risk genes should also be included. Conclusion:The biomarkers for ASD diagnosis could be found by taking DEPs and differential metabolites into consideration. Integrating omics data, glycerophospholipid metabolism and N-glycan biosynthesis might play a critical role in the pathogenesis of ASD.

A study of genetic heterogeneity in autism spectrum disorders based on plasma proteomic and metabolomic analysis: multiomics study of autism heterogeneity

“…According to metabolomic analysis, differential metabolites were mostly involved in amino acid and glycerophospholipid metabolism. These differential metabolites and their associated pathways have previously been reported to be associated with ASD 8,22,44 . There are three amino acids that are essential to the development of ASD,that is, L‐glutamic acid, L‐tryptophan, and taurine.…”

“…Using a single‐cell RNA‐sequencing analysis and proteomic approach, a recent study investigated the induced pluripotent stem cell‐derived “brain‐like organs” from children with three different ASD risk genes, 21 which showed that various ASD risk genes are focused on the phenotype of neuronal developmental asynchrony but mostly diverge at the level of molecular targets 21 . Very recently, we carried out proteomic and metabolomic studies in the plasma of ASD children with five different risk genes ( de novo mutations), as well as proteomics studies of peripheral blood mononuclear cells 22 . The results show that children with ASD were heterogeneous at the genetic level, but differentially expressed proteins (DEPs) and differential metabolites in plasma could still be used to differentiate cases from controls 22 .…”

Proteomic Study on the Mechanism of Arsenic Neurotoxicity in the Rat Cerebral Cortex and the Protective Mechanism of Dictyophora Polysaccharides against Arsenic Neurotoxicity

“…An Eksigent ekspert TM microLC System coupled with a Triple TOF 6600 quadrupole time-of-flight mass spectrometer (SCIEX) was used for analytical separation of peptides. , For analysis of information-dependent acquisition (IDA), 15 μg of sample was first injected onto a ChromXP C18 (5 μm, 0.3 mm × 10 mm, 120 Å, Eksigent) trap cartridge for preconcentration and desalted with 100% solvent A (water/acetonitrile/formic acid (A, 98/2/0.1%; B, 2/98/0.1%)), at 10 μL/min for 3 min before switching to the analytical column. Peptides were eluted from the microfluidic analytical column packed with ChromXP C18 (3 μm, 0.3 mm × 150 mm, 120 Å, Eksigent) using a gradient elution with solvents A and B at 5 μL/min for 60 min.…”

A live-cell platform to isolate phenotypically defined subpopulations for spatial multi-omic profiling

“…In this instance, SaGA can be readily utilized to answer questions governing cell fate decision making. Similarly, neurological diseases also highlight intercellular heterogeneity 34 . One example is Alzheimer's disease in which microglia, specialized tissue-resident macrophages in the central nervous system, have distinct localization patterning 35 .…”