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Revolutionary Database Developed

What a milestone: Scientists have developed the initial database containing the precise makeup of 57,000 proteins found in blood cells. This breakthrough has enabled the improvement of the ability to anticipate if individuals who receive liver transplants will reject their new organ.

The human body contains various types of cells in the blood and bone marrow. Each of them with unique functions and protein expressions. Proteins, composed of amino acids, derive from specific genes in the DNA. Genetic variations or modifications during protein production create unique proteoforms. Proteomics refers to the study of proteins in cells, tissues, or organisms. "Bottom-up" proteomics (BUP) uses enzymes to digest proteins into small peptides. In contrast, "top-down" proteomics (TDP) analyzes intact proteins, identifying their modifications.

Blood Proteoform Atlas (BPA) enables prediction of liver transplant rejection

To study the proteoform composition of human blood and bone marrow cells, 21 different cell types were isolated and analyzed by TDP, creating the Blood Proteoform Atlas (BPA). The BPA contains almost 57,000 proteoforms from over 9,000 genes, forming the first human blood proteoform repository. The BPA provides a foundation for advancing fundamental knowledge of proteins in human cell types. This helps physicians to provide patient-tailored treatments and also supports the development of new clinical tests in the future.

The BPA was also used to find specific proteoforms that could predict graft rejection in liver transplanted patients. By comparing the total amount of proteoforms in white blood cells from three liver transplant groups, 61 proteoforms were identified that have their amounts increased or decreased in the comparisons between the three experimental groups. A new assay that analyzed the 61 proteoforms of interest in a targeted fashion was developed and used to interrogate a new set of samples. 24 proteoform candidates were identified that can potentially help diagnose liver rejection and be used in a future clinical test.

In summary, studying proteoforms improves our understanding of human health and disease status, and the BPA is a foundational resource for advancing knowledge of proteins in human cell types. This provides better indicators of cell type and also supports the development of new clinical tests in the future.

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