Publications
1. Romero-Garcia, Rafael; Mandal, Ayan S; Bethlehem, Richard A I; Crespo-Facorro, Benedicto; Hart, Michael G; Suckling, John
Transcriptomic and connectomic correlates of differential
spatial patterning among gliomas Journal Article
In: Brain, vol. 146, no. 3, pp. 1200–1211, 2023.
Abstract | BibTeX | Tags: connectomic; gene expression; glioma; transcriptomic
@article{Romero-Garcia2023-rx,
title = {Transcriptomic and connectomic correlates of differential
spatial patterning among gliomas},
author = {Rafael Romero-Garcia and Ayan S Mandal and Richard A I Bethlehem and Benedicto Crespo-Facorro and Michael G Hart and John Suckling},
year = {2023},
date = {2023-03-01},
journal = {Brain},
volume = {146},
number = {3},
pages = {1200–1211},
publisher = {Oxford University Press (OUP)},
abstract = {Unravelling the complex events driving grade-specific spatial
distribution of brain tumour occurrence requires rich datasets
from both healthy individuals and patients. Here, we combined
open-access data from The Cancer Genome Atlas, the UK Biobank
and the Allen Brain Human Atlas to disentangle how the different
spatial occurrences of glioblastoma multiforme and low-grade
gliomas are linked to brain network features and the normative
transcriptional profiles of brain regions. From MRI of brain
tumour patients, we first constructed a grade-related frequency
map of the regional occurrence of low-grade gliomas and the more
aggressive glioblastoma multiforme. Using associated mRNA
transcription data, we derived a set of differential gene
expressions from glioblastoma multiforme and low-grade gliomas
tissues of the same patients. By combining the resulting values
with normative gene expressions from post-mortem brain tissue,
we constructed a grade-related expression map indicating which
brain regions express genes dysregulated in aggressive gliomas.
Additionally, we derived an expression map of genes previously
associated with tumour subtypes in a genome-wide association
study (tumour-related genes). There were significant
associations between grade-related frequency, grade-related
expression and tumour-related expression maps, as well as
functional brain network features (specifically, nodal strength
and participation coefficient) that are implicated in
neurological and psychiatric disorders. These findings identify
brain network dynamics and transcriptomic signatures as key
factors in regional vulnerability for glioblastoma multiforme
and low-grade glioma occurrence, placing primary brain tumours
within a well established framework of neurological and
psychiatric cortical alterations.},
keywords = {connectomic; gene expression; glioma; transcriptomic},
pubstate = {published},
tppubtype = {article}
}
Unravelling the complex events driving grade-specific spatial
distribution of brain tumour occurrence requires rich datasets
from both healthy individuals and patients. Here, we combined
open-access data from The Cancer Genome Atlas, the UK Biobank
and the Allen Brain Human Atlas to disentangle how the different
spatial occurrences of glioblastoma multiforme and low-grade
gliomas are linked to brain network features and the normative
transcriptional profiles of brain regions. From MRI of brain
tumour patients, we first constructed a grade-related frequency
map of the regional occurrence of low-grade gliomas and the more
aggressive glioblastoma multiforme. Using associated mRNA
transcription data, we derived a set of differential gene
expressions from glioblastoma multiforme and low-grade gliomas
tissues of the same patients. By combining the resulting values
with normative gene expressions from post-mortem brain tissue,
we constructed a grade-related expression map indicating which
brain regions express genes dysregulated in aggressive gliomas.
Additionally, we derived an expression map of genes previously
associated with tumour subtypes in a genome-wide association
study (tumour-related genes). There were significant
associations between grade-related frequency, grade-related
expression and tumour-related expression maps, as well as
functional brain network features (specifically, nodal strength
and participation coefficient) that are implicated in
neurological and psychiatric disorders. These findings identify
brain network dynamics and transcriptomic signatures as key
factors in regional vulnerability for glioblastoma multiforme
and low-grade glioma occurrence, placing primary brain tumours
within a well established framework of neurological and
psychiatric cortical alterations.