PT  - JOURNAL ARTICLE
AU  - N. Leigh Anderson
AU  - Morteza Razavi
AU  - Matthew E. Pope
AU  - Richard Yip
AU  - Terry W. Pearson
TI  - Multiplexed measurement of protein biomarkers in high-frequency longitudinal dried blood spot (DBS) samples: characterization of inflammatory responses
AID  - 10.1101/643239
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 643239
4099  - http://biorxiv.org/content/early/2019/05/20/643239.short
4100  - http://biorxiv.org/content/early/2019/05/20/643239.full
AB  - A detailed understanding of changes in blood protein biomarkers occuring in individuals over time would enable truly personalized approaches to health and disease monitoring. Such measurements could reveal smaller, earlier departures from normal baseline levels of biomarkers thus allowing better disease detection and treatment monitoring. Current practice, however, generally involves infrequent, sporadic biomarker testing, and this undersampling likely fails to capture important biological phenomena. Here we report the use of a robust multiplex immuno-mass spectrometric method (SISCAPA) to measure a panel of clinically-relevant proteins in a unique collection of 1,522 dried blood spots collected longitudinally by 8 individuals over periods of up to 9 years, with daily sampling during some intervals. Analytical workflow CVs of 2-6% for most assays were achieved by normalizing DBS plasma volume using a set of 3 minimally varying proteins, facilitating temporal analysis of both high- and low-amplitude biomarker changes compared to personalized baselines. The biomarkers included a panel of 9 positive and 5 negative acute phase response (inflammatory) proteins, allowing longitudinal analysis of inflammation markers associated with major and minor infections, influenza vaccination, recovery from hip-replacement surgery and Crohn’s disease. The results illustrate complex time-dependent “biomarker trajectories” on multiple timescales and provide a basis for detailed personalized models of inflammation dynamics. The striking stability of most biomarker protein levels over time, combined with the convenience of self-sampling and low cost of multiplexed measurements using mass spectrometry, provide a new window into the temporal dynamics of disease processes. The extensive results obtained using this high throughput approach offer a new source of precision biomarker ‘big data’ amenable to machine learning approaches and application to more personalized health monitoring.