University of California, Santa Cruz, CA, USA.
BMC Bioinformatics. 2023 Apr 25;24(1):166. doi: 10.1186/s12859-023-05295-z.
BACKGROUND: Wound healing involves careful coordination among various cell types carrying out unique or even multifaceted functions. The abstraction of this complex dynamic process into four primary wound stages is essential to the study of wound care for timing treatment and tracking wound progression. For example, a treatment that may promote healing in the inflammatory stage may prove detrimental in the proliferative stage. Additionally, the time scale of individual responses varies widely across and within the same species. Therefore, a robust method to assess wound stages can help advance translational work from animals to humans. RESULTS: In this work, we present a data-driven model that robustly identifies the dominant wound healing stage using transcriptomic data from biopsies gathered from mouse and human wounds, both burn and surgical. A training dataset composed of publicly available transcriptomic arrays is used to derive 58 shared genes that are commonly differentially expressed. They are divided into 5 clusters based on temporal gene expression dynamics. The clusters represent a 5-dimensional parametric space containing the wound healing trajectory. We then create a mathematical classification algorithm in the 5-dimensional space and demonstrate that it can distinguish between the four stages of wound healing: hemostasis, inflammation, proliferation, and remodeling. CONCLUSIONS: In this work, we present an algorithm for wound stage detection based on gene expression. This work suggests that there are universal characteristics of gene expression in wound healing stages despite the seeming disparities across species and wounds. Our algorithm performs well for human and mouse wounds of both burn and surgical types. The algorithm has the potential to serve as a diagnostic tool that can advance precision wound care by providing a way of tracking wound healing progression with more accuracy and finer temporal resolution compared to visual indicators. This increases the potential for preventive action.
背景:伤口愈合涉及各种细胞类型的精心协调,这些细胞执行独特甚至多方面的功能。将这个复杂的动态过程抽象为四个主要的伤口阶段,对于研究伤口护理的时机治疗和跟踪伤口进展至关重要。例如,在炎症阶段可能促进愈合的治疗方法在增殖阶段可能会造成伤害。此外,个体反应的时间尺度在不同物种之间和同一物种内差异很大。因此,一种稳健的方法来评估伤口阶段可以帮助将从动物到人类的转化工作推进。
结果:在这项工作中,我们提出了一种数据驱动的模型,该模型使用从小鼠和人类烧伤和手术伤口活检中收集的转录组数据,稳健地识别主导的伤口愈合阶段。一个由公开可用的转录组阵列组成的训练数据集用于得出 58 个共同差异表达的共享基因。它们根据时间基因表达动态分为 5 个簇。这些簇代表一个包含伤口愈合轨迹的 5 维参数空间。然后,我们在 5 维空间中创建一个数学分类算法,并证明它可以区分伤口愈合的四个阶段:止血、炎症、增殖和重塑。
结论:在这项工作中,我们提出了一种基于基因表达的伤口阶段检测算法。这项工作表明,尽管物种和伤口之间存在明显差异,但在伤口愈合阶段存在普遍的基因表达特征。我们的算法对烧伤和手术类型的人类和小鼠伤口都有很好的效果。该算法有可能成为一种诊断工具,通过提供一种比视觉指标更准确和更精细的时间分辨率来跟踪伤口愈合进展,从而提高精准伤口护理的潜力。这增加了采取预防措施的可能性。
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