Roder Joanna, Net Lelia, Oliveira Carlos, Meyer Krista, Asmellash Senait, Kasimir-Bauer Sabine, Pass Harvey, Weber Jeffrey, Roder Heinrich, Grigorieva Julia
Biodesix, Inc, 2970 Wilderness Place, Boulder, CO 80301, USA.
Department of Gynecology and Obstetrics, University Hospital of Essen, Hufelandstrasse 55, 45147 Essen, Germany.
Clin Mass Spectrom. 2020 Sep 9;18:13-26. doi: 10.1016/j.clinms.2020.09.001. eCollection 2020 Nov.
Most diseases involve a complex interplay between multiple biological processes at the cellular, tissue, organ, and systemic levels. Clinical tests and biomarkers based on the measurement of a single or few analytes may not be able to capture the complexity of a patient's disease. Novel approaches for comprehensively assessing biological processes from easily obtained samples could help in the monitoring, treatment, and understanding of many conditions.
We propose a method of creating scores associated with specific biological processes from mass spectral analysis of serum samples.
A score for a process of interest is created by: (i) identifying mass spectral features associated with the process using set enrichment analysis methods, and (ii) combining these features into a score using a principal component analysis-based approach. We investigate the creation of scores using cohorts of patients with non-small cell lung cancer, melanoma, and ovarian cancer. Since the circulating proteome is amenable to the study of immune responses, which play a critical role in cancer development and progression, we focus on functions related to the host response to disease.
We demonstrate the feasibility of generating scores, their reproducibility, and their associations with clinical outcomes. Once the scores are constructed, only 3 µL of serum is required for the assessment of multiple biological functions from the circulating proteome.
These mass spectrometry-based scores could be useful for future multivariate biomarker or test development studies for informing treatment, disease monitoring and improving understanding of the roles of various biological functions in multiple disease settings.
大多数疾病涉及细胞、组织、器官和全身水平上多个生物过程之间的复杂相互作用。基于单一或少数分析物测量的临床试验和生物标志物可能无法捕捉患者疾病的复杂性。从易于获取的样本中全面评估生物过程的新方法有助于多种疾病的监测、治疗和理解。
我们提出一种从血清样本的质谱分析中创建与特定生物过程相关分数的方法。
通过以下方式为感兴趣的过程创建分数：(i) 使用集富集分析方法识别与该过程相关的质谱特征，以及 (ii) 使用基于主成分分析的方法将这些特征组合成一个分数。我们使用非小细胞肺癌、黑色素瘤和卵巢癌患者队列研究分数的创建。由于循环蛋白质组适合研究免疫反应，而免疫反应在癌症发展和进展中起关键作用，我们专注于与宿主对疾病反应相关的功能。
我们证明了生成分数的可行性、其可重复性以及它们与临床结果的关联。一旦构建了分数，仅需3微升血清即可从循环蛋白质组中评估多种生物学功能。
这些基于质谱的分数可能有助于未来多变量生物标志物或测试开发研究，为治疗、疾病监测提供信息，并增进对多种疾病环境中各种生物学功能作用的理解。
