RT Journal Article
SR Electronic
T1 Automatic identification of informative regions with epigenomic changes associated to hematopoiesis
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 082917
DO 10.1101/082917
A1 Enrique Carrillo-de-Santa-Pau
A1 David Juan
A1 Vera Pancaldi
A1 Felipe Were
A1 Ignacio Martin-Subero
A1 Daniel Rico
A1 Alfonso Valencia
A1 on behalf of The BLUEPRINT Consortium
YR 2017
UL http://biorxiv.org/content/early/2017/06/20/082917.abstract
AB 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 forty-two 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