Moscow Institute of Physics and Technology, Moscow, Russia; OmicsWay Corporation, Walnut, CA, United States; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russia; World-Class Research Center "Digital biodesign and personalized healthcare", Sechenov First Moscow State Medical University, Moscow, Russia.
Moscow Institute of Physics and Technology, Moscow, Russia; OmicsWay Corporation, Walnut, CA, United States.
Adv Protein Chem Struct Biol. 2021;127:1-53. doi: 10.1016/bs.apcsb.2021.02.005. Epub 2021 Apr 5.
Analysis of molecular pathway activation is the recent instrument that helps to quantize activities of various intracellular signaling, structural, DNA synthesis and repair, and biochemical processes. This may have a deep impact in fundamental research, bioindustry, and medicine. Unlike gene ontology analyses and numerous qualitative methods that can establish whether a pathway is affected in principle, the quantitative approach has the advantage of exactly measuring the extent of a pathway up/downregulation. This results in emergence of a new generation of molecular biomarkers-pathway activation levels, which reflect concentration changes of all measurable pathway components. The input data can be the high-throughput proteomic or transcriptomic profiles, and the output numbers take both positive and negative values and positively reflect overall pathway activation. Due to their nature, the pathway activation levels are more robust biomarkers compared to the individual gene products/protein levels. Here, we review the current knowledge of the quantitative gene expression interrogation methods and their applications for the molecular pathway quantization. We consider enclosed bioinformatic algorithms and their applications for solving real-world problems. Besides a plethora of applications in basic life sciences, the quantitative pathway analysis can improve molecular design and clinical investigations in pharmaceutical industry, can help finding new active biotechnological components and can significantly contribute to the progressive evolution of personalized medicine. In addition to the theoretical principles and concepts, we also propose publicly available software for the use of large-scale protein/RNA expression data to assess the human pathway activation levels.
分子通路激活分析是一种最近的工具,可以帮助量化各种细胞内信号、结构、DNA 合成和修复以及生化过程的活性。这可能会对基础研究、生物产业和医学产生深远的影响。与可以确定通路是否受到影响的基因本体分析和众多定性方法不同,定量方法具有精确测量通路上调/下调程度的优势。这导致了新一代分子生物标志物——通路激活水平的出现,它反映了所有可测量通路成分浓度的变化。输入数据可以是高通量蛋白质组学或转录组学谱,输出数值取正值和负值,并正向反映整体通路激活。由于其性质,与单个基因产物/蛋白水平相比,通路激活水平是更稳健的生物标志物。在这里,我们回顾了定量基因表达检测方法的现有知识及其在分子通路量化中的应用。我们考虑了包含的生物信息学算法及其在解决实际问题中的应用。除了在基础生命科学中有大量应用外,定量通路分析还可以改进药物行业的分子设计和临床研究,帮助寻找新的活性生物技术成分,并为个性化医学的不断发展做出重大贡献。除了理论原理和概念外,我们还提出了可用于评估人类通路激活水平的公共可用软件,用于大规模蛋白质/RNA 表达数据。