A proposal for score assignment to characterize biological processes from mass spectral analysis of serum.

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.

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© 2020 The Authors.

Déclaration de conflit d'intérêts

Joanna Roder, Heinrich Roder, Julia Grigorieva, Lelia Net, Senait Asmellash, Carlos Oliveira, and Krista Meyer are or were employees of Biodesix, Inc. and have or had stock or stock options in Biodesix, Inc. Joanna Roder, Heinrich Roder and Carlos Oliveria are inventors on related patents assigned to Biodesix, Inc. Sabine Kasimir-Bauer, Harvey Pass and Jeffrey Weber declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.