| Autor: |
Jang MK; Genomic Research Alliance for Transplantation (GRAfT) and Laboratory of Applied Precision. Omics, National Heart, Lung, and Blood Institute (NHLBI), NIH, Bethesda, MD., Markowitz TE; NIAID Collaborative Bioinformatics Resource, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD., Andargie TE; Genomic Research Alliance for Transplantation (GRAfT) and Laboratory of Applied Precision. Omics, National Heart, Lung, and Blood Institute (NHLBI), NIH, Bethesda, MD., Apalara Z; Genomic Research Alliance for Transplantation (GRAfT) and Laboratory of Applied Precision. Omics, National Heart, Lung, and Blood Institute (NHLBI), NIH, Bethesda, MD., Kuhn S; NIAID Collaborative Bioinformatics Resource, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD., Agbor-Enoh S; Genomic Research Alliance for Transplantation (GRAfT) and Laboratory of Applied Precision. Omics, National Heart, Lung, and Blood Institute (NHLBI), NIH, Bethesda, MD.; Department of Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD. |
| Abstrakt: |
Patient monitoring is a cornerstone in clinical practice to define disease phenotypes and guide clinical management. Unfortunately, this is often reliant on invasive and/or less sensitive methods that do not provide deep phenotype assessments of disease state to guide treatment. This paper examined plasma cell-free DNA chromatin immunoprecipitation sequencing (cfChIP-seq) to define molecular gene sets in physiological and heart transplant patients taking immunosuppression medications. We show cfChIP-seq reliably detect gene signals that correlate with gene expression. In healthy controls and in heart transplant patients, cfChIP-seq reliably detected housekeeping genes. cfChIP-seq identified differential gene signals of the relevant immune and non-immune molecular pathways that were predominantly downregulated in immunosuppressed heart transplant patients compared to healthy controls. cfChIP-seq also identified tissue sources of cfDNA, detecting greater cell-free DNA from cardiac, hematopoietic, and other non-hematopoietic tissues such as the pulmonary, digestive, and neurological tissues in transplant patients than healthy controls. cfChIP-seq gene signals were reproducible between patient populations and blood collection methods. cfChIP-seq may therefore be a reliable approach to provide dynamic assessments of molecular pathways and tissue injury associated to disease. |
