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Cell-free Chromatin Immunoprecipitation to detect molecular pathways in Physiological and Disease States

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...

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Autores principales: Jang, Moon K., Markowitz, Tovah E., Andargie, Temesgen E., Apalara, Zainab, Kuhn, Skyler, Agbor-Enoh, Sean
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9928031/
https://www.ncbi.nlm.nih.gov/pubmed/36789421
http://dx.doi.org/10.1101/2023.01.24.525414
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author Jang, Moon K.
Markowitz, Tovah E.
Andargie, Temesgen E.
Apalara, Zainab
Kuhn, Skyler
Agbor-Enoh, Sean
author_facet Jang, Moon K.
Markowitz, Tovah E.
Andargie, Temesgen E.
Apalara, Zainab
Kuhn, Skyler
Agbor-Enoh, Sean
author_sort Jang, Moon K.
collection PubMed
description 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.
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spelling pubmed-99280312023-02-15 Cell-free Chromatin Immunoprecipitation to detect molecular pathways in Physiological and Disease States Jang, Moon K. Markowitz, Tovah E. Andargie, Temesgen E. Apalara, Zainab Kuhn, Skyler Agbor-Enoh, Sean bioRxiv Article 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. Cold Spring Harbor Laboratory 2023-01-25 /pmc/articles/PMC9928031/ /pubmed/36789421 http://dx.doi.org/10.1101/2023.01.24.525414 Text en https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/) , which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use.
spellingShingle Article
Jang, Moon K.
Markowitz, Tovah E.
Andargie, Temesgen E.
Apalara, Zainab
Kuhn, Skyler
Agbor-Enoh, Sean
Cell-free Chromatin Immunoprecipitation to detect molecular pathways in Physiological and Disease States
title Cell-free Chromatin Immunoprecipitation to detect molecular pathways in Physiological and Disease States
title_full Cell-free Chromatin Immunoprecipitation to detect molecular pathways in Physiological and Disease States
title_fullStr Cell-free Chromatin Immunoprecipitation to detect molecular pathways in Physiological and Disease States
title_full_unstemmed Cell-free Chromatin Immunoprecipitation to detect molecular pathways in Physiological and Disease States
title_short Cell-free Chromatin Immunoprecipitation to detect molecular pathways in Physiological and Disease States
title_sort cell-free chromatin immunoprecipitation to detect molecular pathways in physiological and disease states
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9928031/
https://www.ncbi.nlm.nih.gov/pubmed/36789421
http://dx.doi.org/10.1101/2023.01.24.525414
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