Untargeted metabolomic, and proteomic analysis identifies metabolic biomarkers and pathway alterations in individuals with 22q11.2 deletion syndrome

Author:

Zafarullah Marwa,Angkustsiri Kathleen,Quach Austin,Yeo Seungjun,Durbin-Johnson Blythe P.,Bowling Heather,Tassone Flora

Abstract

Abstract Introduction The chromosome 22q11.2 deletion syndrome (22q11.2DS) is characterized by a well-defined microdeletion and is associated with a wide range of brain-related phenotypes including schizophrenia spectrum disorders (SCZ), autism spectrum disorders (ASD), anxiety disorders and attention deficit disorders (ADHD). The typically deleted region in 22q11.2DS contains multiple genes which haploinsufficiency has the potential of altering the protein and the metabolic profiles. Objectives Alteration in metabolic processes and downstream protein pathways during the early brain development may help to explain the increased prevalence of the observed neurodevelopmental phenotypes in 22q11.2DS. However, relatively little is known about the correlation of dysregulated protein/metabolite expression and neurobehavioral impairments in individuals who developed them over time. Methods In this study, we performed untargeted metabolic and proteomic analysis in plasma samples derived from 30 subjects including 16 participants with 22q11.2DS and 14 healthy controls (TD) enrolled in a longitudinal study, aiming to identify a metabolic and protein signature informing about the underlying mechanisms involved in disease development and progression. The metabolic and proteomic profiles were also compared between the participants with 22q11.2DS with and without various comorbidities, such as medical involvement, psychiatric conditions, and autism spectrum disorder (ASD) to detect potential changes among multiple specimens, collected overtime, with the aim to understand the basic underlying mechanisms involved in disease development and progression. Results We observed a large number of statistically significant differences in metabolites between the two groups. Among them, the levels of taurine and arachidonic acid were significantly lower in 22q11.2DS compared to the TD group. In addition, we identified 16 proteins that showed significant changes in expression levels (adjusted P < 0.05) in 22q11.2DS as compared to TD, including those involved in 70 pathways such as gene expression, the PI3K-Akt signaling pathway and the complement system. Within participants with 22q11.2DS, no significant changes in those with and without medical or psychiatric conditions were observed. Conclusion To our knowledge, this is the first report on plasma metabolic and proteomic profiling and on the identification of unique biomarkers in 22q11.2DS. These findings may suggest the potential role of the identified metabolites and proteins as biomarkers for the onset of comorbid conditions in 22q11.2DS. Ultimately, the altered protein pathways in 22q11.2DS may provide insights of the biological mechanisms underlying the neurodevelopmental phenotype and may provide missing molecular outcome measures in future clinical trials to assess early-diagnosis treatment and the efficacy of response to targeted treatment.

Publisher

Springer Science and Business Media LLC

Reference88 articles.

1. Akar, N. A., & Adekile, A. D. (2007). Chromosome 22q11.2 deletion presenting with immune-mediated cytopenias, macrothrombocytopenia and platelet dysfunction. Medical Principles and Practice: International Journal of tHe Kuwait University, Health Science Centre, 16(4), 318. https://doi.org/10.1159/000102157

2. Almeida, N., Rodriguez, J., Parada, I. P., Perez-Riverol, Y., Woldmar, N., Kim, Y., Oskolas, H., Betancourt, L., Valdés, J. G., Barbara Sahlin, K., Luciana Pizzatti, A., Szasz, M., Kárpáti, S., Appelqvist, R., Malm, J., Domont, G. B., Nogueira, F. C. S., Marko-Varga, G., & Sanchez, A. (2021). Mapping the melanoma plasma proteome (MPP) using single-shot proteomics interfaced with the WiMT database. Cancers. https://doi.org/10.3390/cancers13246224

3. Alshweki, A., Muñuzuri, A. P., Baña, A. M., José de Castro, M., Andrade, F., Aldamiz-Echevarría, L., Sáenz, M., de Pipaón, J. M., Fraga, M. L., & Couce,. (2015). Effects of different arachidonic acid supplementation on psychomotor development in very preterm infants; a randomized controlled trial. Nutrition Journal, 14, 101.

4. Antshel, K. M., Fremont, W., Ramanathan, S., & Kates, W. R. (2016). Predicting cognition and psychosis in young adults with 22q11.2 deletion syndrome. Schizophrenia Bulletin, 43(4), 833–842.

5. Antshel, K. M., Kates, W. R., Roizen, N., Fremont, W., & Shprintzen, R. J. (2005). 22q11.2 deletion syndrome: genetics, neuroanatomy and cognitive/behavioral features keywords. Child Neuropsychology: A Journal on Normal and Abnormal Development in Childhood and Adolescence, 11(1), 5–19.

Cited by 2 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3