Computational identification of phospho-tyrosine sub-networks related to acanthocyte generation in neuroacanthocytosis.

PloS One
L De FranceschiCarlo Laudanna

Abstract

Acanthocytes, abnormal thorny red blood cells (RBC), are one of the biological hallmarks of neuroacanthocytosis syndromes (NA), a group of rare hereditary neurodegenerative disorders. Since RBCs are easily accessible, the study of acanthocytes in NA may provide insights into potential mechanisms of neurodegeneration. Previous studies have shown that changes in RBC membrane protein phosphorylation state affect RBC membrane mechanical stability and morphology. Here, we coupled tyrosine-phosphoproteomic analysis to topological network analysis. We aimed to predict signaling sub-networks possibly involved in the generation of acanthocytes in patients affected by the two core NA disorders, namely McLeod syndrome (MLS, XK-related, Xk protein) and chorea-acanthocytosis (ChAc, VPS13A-related, chorein protein). The experimentally determined phosphoproteomic data-sets allowed us to relate the subsequent network analysis to the pathogenetic background. To reduce the network complexity, we combined several algorithms of topological network analysis including cluster determination by shortest path analysis, protein categorization based on centrality indexes, along with annotation-based node filtering. We first identified XK- and VPS13A-rela...Continue Reading

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Citations

Mar 15, 2014·Current Opinion in Hematology·Lucia De FranceschiNarla Mohandas
Oct 21, 2015·Frontiers in Immunology·Qianqian Zhang, Fadi G Lakkis
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Jan 28, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Michela MirendaCarlo Laudanna

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Methods Mentioned

BETA
GTPases
Protein Assay
electrophoresis

Software Mentioned

CentiScaPe
ClueGO
Progenesis Same Spots
ImageJ
BiNGO
Pesca
Cytoscape

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