Paulovich - ISPRM_breast_cancer_human_plasma_protein_biomarkers_early_detection

Triage of >1300 candidate biomarkers in plasma using internal standard-triggered parallel reaction monitoring mass spectrometry
  • Organism: Homo sapiens
  • Instrument: Orbitrap Eclipse
  • SpikeIn: Yes
  • Keywords: Human, Plasma, Breast cancer, Protein, IS-PRM
  • Lab head: Jeff Whiteaker Submitter: Jacob Kennedy
Abstract
Despite advances in proteomic technologies, clinical translation of plasma biomarkers remains low, partly due to a major bottleneck between the discovery of hundreds of candidate biomarkers and downstream costly clinical validation studies. Due to a dearth of multiplexable assays, generally only a few candidate biomarkers are tested, and the validation success rate is accordingly low. Here, we demonstrate the capability of internal standard triggered parallel reaction monitoring (IS-PRM) to prioritize candidate biomarkers for validation studies. A 5,176-plex IS-PRM assay was developed and implemented in human plasma to quantify peptides representing 1,314 breast cancer biomarker candidates. Compared to prior approaches using data-dependent analysis, IS-PRM showed improved sensitivity and precision and enabled rank-ordering of candidate biomarkers for validation studies. The method greatly expands the capabilities for quantification of large numbers of proteins and is well suited for large-scale prioritization of viable candidate biomarkers.
Created on 9/2/21, 7:24 PM
Clustergrammer Heatmap
 
Download
ISPRM_Characterization_MCF10A_curve_F06_2021-09-23_14-48-57.sky.zip2021-09-28 09:06:021,3145,17610,35261,95815
ISPRM_Characterization_MCF10A_curve_F03_2021-09-16_10-53-20.sky.zip2021-09-28 08:58:251,3145,17610,35261,93815
ISPRM_Characterization_MCF10A_curve_F05_2021-09-16_09-18-29.sky.zip2021-09-28 08:51:151,3145,17610,35261,99615
ISPRM_Characterization_MCF10A_curve_F04_2021-09-16_10-36-00.sky.zip2021-09-28 08:43:591,3145,17610,35261,98815
ISPRM_Characterization_MCF10A_curve_F01_2021-09-15_15-41-53.sky.zip2021-09-28 08:36:491,3145,17610,35261,85815
ISPRM_Characterization_MCF10A_curve_F02_2021-09-16_10-19-43.sky.zip2021-09-28 08:29:131,3145,17610,35261,90815
ISPRM_Application_Hs_Plasma_Pool_1_TNBC_2021-09-10_11-00-12.sky.zip2021-09-28 07:47:201,3145,17610,35261,34824
ISPRM_Application_Hs_Plasma_Pool_2_HER2p_2021-09-10_13-06-56.sky.zip2021-09-14 13:05:181,3145,17610,35261,74424
ISPRM_Application_Hs_Plasma_Pool_3_ERp_HER2n_2021-09-10_13-41-00.sky.zip2021-09-14 12:55:511,3145,17610,35261,71024
ISPRM_Application_Hs_Plasma_Pool_4_Atypia_2021-09-10_14-27-58.sky.zip2021-09-14 12:46:581,3145,17610,35261,68224
ISPRM_Application_Hs_Plasma_Pool_5_Non_prolif_2021-09-10_16-04-28.sky.zip2021-09-14 12:35:101,3145,17610,35261,81824
ISPRM_Application_Hs_Plasma_Pool_6_Prolif_2021-09-13_09-02-33.sky.zip2021-09-14 12:26:201,3145,17610,35261,22424
ISPRM_Application_Blank_yeast_reps_2021-09-13_09-37-01.sky.zip2021-09-14 12:16:531,3145,17610,35262,09696
ISPRM_Development_Hs_Plasma_Pool_X_2021-09-13_13-01-53.sky.zip2021-09-14 11:48:231,3145,17610,35262,10012
ISPRM_Development_Hs_Plasma_Pool_X_directed_DDA_2021-09-13_13-56-39.sky.zip2021-09-14 11:41:331,3145,1768,173151,36512
ISPRM_Development_yeast_directed_DDA_2021-09-13_14-32-04.sky.zip2021-09-14 11:32:241,3145,1768,173151,36512