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Automatic identification of informative regions with epigenomic changes associated to hematopoiesis

Lookup NU author(s): Dr Daniel Rico RodriguezORCiD

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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).


Abstract

Hematopoiesis is one of the best characterized biological systems but the connection between chromatin changes and lineage differentiation is not yet well understood. We have developed a bioinformatic workflow to generate a chromatin space that allows to classify 42 human healthy blood epigenomes from the BLUEPRINT, NIH ROADMAP and ENCODE consortia by their cell type. This approach let us to distinguish different cells types based on their epigenomic profiles, thus recapitulating important aspects of human hematopoiesis. The analysis of the orthogonal dimension of the chromatin space identify 32,662 chromatin determinant regions (CDRs), genomic regions with different epigenetic characteristics between the cell types. Functional analysis revealed that these regions are linked with cell identities. The inclusion of leukemia epigenomes in the healthy hematological chromatin sample space gives us insights on the healthy cell types that are more epigenetically similar to the disease samples. Further analysis of tumoral epigenetic alterations in hematopoietic CDRs points to sets of genes that are tightly regulated in leukemic transformations and commonly mutated in other tumors. Our method provides an analytical approach to study the relationship between epigenomic changes and cell lineage differentiation. Method availability: https://github.com/david-juan/ChromDet.


Publication metadata

Author(s): Carrillo-de-Santa-Pau E, Juan D, Pancaldi V, Were F, Martin-Subero I, Rico D, Valencia A, The BLUEPRINT Consortium

Publication type: Article

Publication status: Published

Journal: Nucleic Acids Research

Year: 2017

Volume: 45

Issue: 16

Pages: 9244-9259

Print publication date: 19/12/2017

Online publication date: 17/08/2017

Acceptance date: 06/07/2017

Date deposited: 11/09/2017

ISSN (print): 1362-4954

ISSN (electronic): 0305-1048

Publisher: Oxford University Press

URL: https://doi.org/10.1093/nar/gkx618

DOI: 10.1093/nar/gkx618


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Funding

Funder referenceFunder name
282510
BFU2015–71241-R

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