Differential network analysis and protein-protein interaction study reveals active protein modules in glucocorticoid resistance for infant acute lymphoblastic leukemia

Molecular Medicine
Zaynab MousavianAli Masoudi-Nejad

Abstract

Acute lymphoblastic leukemia (ALL) is the most common type of cancer diagnosed in children and Glucocorticoids (GCs) form an essential component of the standard chemotherapy in most treatment regimens. The category of infant ALL patients carrying a translocation involving the mixed lineage leukemia (MLL) gene (gene KMT2A) is characterized by resistance to GCs and poor clinical outcome. Although some studies examined GC-resistance in infant ALL patients, the understanding of this phenomenon remains limited and impede the efforts to improve prognosis. This study integrates differential co-expression (DC) and protein-protein interaction (PPI) networks to find active protein modules associated with GC-resistance in MLL-rearranged infant ALL patients. A network was constructed by linking differentially co-expressed gene pairs between GC-resistance and GC-sensitive samples and later integrated with PPI networks by keeping the links that are also present in the PPI network. The resulting network was decomposed into two sub-networks, specific to each phenotype. Finally, both sub-networks were clustered into modules using weighted gene co-expression network analysis (WGCNA) and further analyzed with functional enrichment analysis. Throu...Continue Reading

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Datasets Mentioned

BETA
GSE32962

Methods Mentioned

BETA
aminoacylation
ubiquitination

Software Mentioned

DiffCorr R package
BiNGO
db Bioconductor
HIPPIE
hgu133plus2
Database for Annotation Visualization and Integrated Discovery...
GEOquery Bioconductor
Affy Bioconductor package
DiffCorr
VSN Bioconductor

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