Modeling autism: a systems biology approach.

Mary Randolph-Gips, Pramila Srinivasan
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引用次数: 34

Abstract

Autism is the fastest growing developmental disorder in the world today. The prevalence of autism in the US has risen from 1 in 2500 in 1970 to 1 in 88 children today. People with autism present with repetitive movements and with social and communication impairments. These impairments can range from mild to profound. The estimated total lifetime societal cost of caring for one individual with autism is $3.2 million US dollars. With the rapid growth in this disorder and the great expense of caring for those with autism, it is imperative for both individuals and society that techniques be developed to model and understand autism. There is increasing evidence that those individuals diagnosed with autism present with highly diverse set of abnormalities affecting multiple systems of the body. To this date, little to no work has been done using a whole body systems biology approach to model the characteristics of this disorder. Identification and modelling of these systems might lead to new and improved treatment protocols, better diagnosis and treatment of the affected systems, which might lead to improved quality of life by themselves, and, in addition, might also help the core symptoms of autism due to the potential interconnections between the brain and nervous system with all these other systems being modeled. This paper first reviews research which shows that autism impacts many systems in the body, including the metabolic, mitochondrial, immunological, gastrointestinal and the neurological. These systems interact in complex and highly interdependent ways. Many of these disturbances have effects in most of the systems of the body. In particular, clinical evidence exists for increased oxidative stress, inflammation, and immune and mitochondrial dysfunction which can affect almost every cell in the body. Three promising research areas are discussed, hierarchical, subgroup analysis and modeling over time. This paper reviews some of the systems disturbed in autism and suggests several systems biology research areas. Autism poses a rich test bed for systems biology modeling techniques.

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孤独症建模:一种系统生物学方法。
自闭症是当今世界上增长最快的发育障碍。自闭症在美国的患病率已经从1970年的1 / 2500上升到今天的1 / 88。自闭症患者表现为重复性动作,社交和沟通障碍。这些损伤从轻微到严重不等。据估计,照顾一名自闭症患者一生的社会总成本为320万美元。随着自闭症患者数量的快速增长和照顾自闭症患者的巨大费用,对个人和社会来说,开发技术来模拟和理解自闭症都是势在必行的。越来越多的证据表明,那些被诊断为自闭症的人表现出高度多样化的异常,影响着身体的多个系统。到目前为止,几乎没有人利用全身系统生物学方法来模拟这种疾病的特征。对这些系统的识别和建模可能会导致新的和改进的治疗方案,更好的诊断和治疗受影响的系统,这可能会提高生活质量,此外,也可能有助于自闭症的核心症状,因为大脑和神经系统之间的潜在联系与所有这些被建模的其他系统。本文首先综述了自闭症影响人体代谢、线粒体、免疫、胃肠和神经系统等多个系统的研究。这些系统以复杂和高度相互依赖的方式相互作用。许多这些干扰对身体的大多数系统都有影响。特别是,临床证据表明,氧化应激、炎症、免疫和线粒体功能障碍增加,几乎可以影响体内的每个细胞。讨论了三个有前途的研究领域:层次分析、子群分析和时间建模。本文综述了孤独症的一些系统干扰,并提出了几个系统生物学的研究方向。自闭症为系统生物学建模技术提供了丰富的实验平台。
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