Paving the Way toward Personalized Medicine: Current Advances and Challenges in Multi-OMICS Approach in Autism Spectrum Disorder for Biomarkers Discovery and Patient Stratification

Abstract

Autism spectrum disorder (ASD) is a multifactorial neurodevelopmental disorder characterized by impairments in two main areas: social/communication skills and repetitive behavioral patterns. The prevalence of ASD has increased in the past two decades, however, it is not known whether the evident rise in ASD prevalence is due to changes in diagnostic criteria or an actual increase in ASD cases. Due to the complexity and heterogeneity of ASD, symptoms vary in severity and may be accompanied by comorbidities such as epilepsy, attention deficit hyperactivity disorder (ADHD), and gastrointestinal (GI) disorders. Identifying biomarkers of ASD is not only crucial to understanding the biological characteristics of the disorder, but also as a detection tool for its early screening. Hence, this review gives an insight into the main areas of ASD biomarker research that show promising findings. Finally, it covers success stories that highlight the importance of precision medicine and the current challenges in ASD biomarker discovery studies.

Methods to Improve Molecular Diagnosis in Genomic Cold Cases in Pediatric Neurology

“…Over the past two decades, its methods have undergone significant expansion and improvement, allowing for the study of protein conformation, function, interactions, and posttranslational modification, among others [ 124 , 125 ]. In the field of ND research, proteomics has been employed in the quest for biomarker discovery (notably in autism) and in the study of the molecular mechanisms of disease [ 126 , 127 , 128 , 129 , 130 ]. In diagnostics, targeted proteomics can assist in assessing the consequences of the genetic variants discovered by NGS [ 131 ].…”

Ways to Address Perinatal Mast Cell Activation and Focal Brain Inflammation, including Response to SARS-CoV-2, in Autism Spectrum Disorder

“…However, ASD pathogenesis is still unknown. Moreover, most children with ASD have a number of comorbidities such as hyperactivity, gastrointestinal problems, allergies, and seizures [ 12 , 13 , 14 ], making the development of effective treatments difficult and prompting the need for a personalized approach [ 15 ].…”

A Personalized Approach to Evaluating and Treating Autism Spectrum Disorder

“…A group of leaders in the treatment of ASD in Argentina describe their approach for defining subgroups by concentrating on the diagnosis and treatment of common concomitant medical problems and propose a classification system based on responses to the treatment of these concomitant problems [4]. A nice overview from a group in Qatar outlines the potential for biomarker use in the stratification of ASD [5]. This paper provides nice illustrations of the various biomarkers and approaches as well as provides some limited examples of the biomarkers described.…”

“…Perhaps most apparent, these articles underline the primacy of mitochondria in ASD, including oxidative stress and redox regulation, which are themselves major functions of mitochondria. Although the connection between ASD and this important cellular organelle is hardly new, this collection of papers serves to demonstrate the ubiquitous nature of the connection, which ranges from mitochondrial aspects in the prenatal and environmental risk factors/exposures [2,3,8] to biomarkers/metabolites [5,8,[12][13][14][15][16], enzymology [12], and the positive response to therapy, at least in part targeting the mitochondria [8,11,12,15,16,18,19].…”