Proteomic Analysis of Whole Blood Using Volumetric Absorptive Microsampling for Precision Medicine Biomarker Studies br

Microsampling of patient blood promises several benefitsover conventional phlebotomy practices to facilitate precision medicinestudies. These include at-home patient blood collection, supportingtelehealth monitoring, minimal postcollection processing, and compati-bility with nonrefrigerated transport and storage. However, for proteomicbiomarker studies, mass spectrometry of whole blood has generally beenavoided in favor of using plasma or serum obtained from venepuncture.We evaluated the use of a volumetric absorptive microsampling (VAMS)device as a sample preparation matrix to enable LC-MS proteomicanalyses of dried whole blood. We demonstrated the detection and robustquantitation of up to 1600 proteins from single-shot shotgun-LC-MSanalysis of dried whole blood, greatly enhancing proteome depth compared with conventional single-shot LC-MS analyses ofundepleted plasma. Some proteins not previously reported in blood were detected using this approach. Various washing reagentswere used to demonstrate that proteins can be preferentially removed from VAMS devices prior to downstream analyses. We providea demonstration that archival frozen blood cell pellets housed under long-term storage (exceeding 5 years) are compatible withVAMS to enable quantitation of potential biomarker proteins from biobank repositories. These demonstrations are important stepsin establishing viable analysis workflows to underpin large-scale precision medicine studies. Data are available via ProteomeXchangewith the identifier PXD028605.