Chen Jason, Coppola Giovanni
Interdepartmental Program in Bioinformatics and Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA, United States.
Interdepartmental Program in Bioinformatics and Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA, United States.
Handb Clin Neurol. 2018;147:75-92. doi: 10.1016/B978-0-444-63233-3.00007-5.
High-throughput, low-cost sequencing technologies have begun to yield new insights into biology and medicine. New data enable the interrogation of the molecular biology of disease from DNA to RNA to protein, charting the central dogma. This chapter reviews some of the key advances and resources in the application of bioinformatics to understanding, and ultimately diagnosing and treating, diseases of the nervous system. Array genotyping, exome sequencing, and whole-genome sequencing, in both disease and healthy populations, have enabled the interpretation of new genetic data. Profiling of epigenetic markers, such as histone modifications, has added to our understanding of the regulatory machinery of the genome. Downstream, mRNA, and protein expression data from published experiments and high-throughput studies enable complex analyses of gene function across many experimental conditions and tissues. Further delineation of molecular mechanism arises from the concept of genes working together in pathways or networks, reflecting direct protein interactions and regulatory relationships. The rapidly moving field of bioinformatics has made significant contributions to neurology in these early days; continued advances promise to transform medicine from basic science to clinical practice, as more genomics data are generated, combined, and analyzed in the future.
高通量、低成本的测序技术已开始为生物学和医学带来新的见解。新数据能够从DNA到RNA再到蛋白质对疾病的分子生物学进行探究，勾勒出中心法则。本章回顾了生物信息学在理解、最终诊断和治疗神经系统疾病方面应用的一些关键进展和资源。在疾病人群和健康人群中进行的阵列基因分型、外显子组测序和全基因组测序，使得对新的遗传数据得以解读。对表观遗传标记（如组蛋白修饰）的分析，加深了我们对基因组调控机制的理解。在下游，来自已发表实验和高通量研究的mRNA和蛋白质表达数据，能够在许多实验条件和组织中对基因功能进行复杂分析。对分子机制的进一步阐释源于基因在通路或网络中协同作用的概念，这反映了直接的蛋白质相互作用和调控关系。在早期，快速发展的生物信息学领域已为神经学做出了重大贡献；随着未来产生、整合和分析更多的基因组数据，持续的进展有望将医学从基础科学转变为临床实践。
