Document Detail


Network analysis of reverse phase protein expression data: characterizing protein signatures in acute myeloid leukemia cytogenetic categories t(8;21) and inv(16).
MedLine Citation:
PMID:  22623292     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Acute myeloid leukemia (AML) patients present with cancerous cells originating from bone marrow. Proteomic data on AML patient cells provides critical information on the key molecules associated with the disease. Here, we introduce a new computational approach to identify complex patterns in protein signaling from reverse phase protein array data. We analyzed the expression of 203 proteins in cells taken from AML patients. Dominant overlapping protein networks between subtypes of AML patients were characterized computationally, through a paired t-test approach looking at relative protein expression. In the first application of this method, we compared recurrent cytogenetic abnormalities inv(16) and t(8;21), both affecting core-binding factor (CBFβ), to normal CD34(+) cells and to each other. Six hundred seventy-eight sets of proteins were identified as significantly different in both inv(16) and t(8;21) compared to controls, at the Bonferroni number, α < 2.44 × 10(-6) . We strengthened our predictions by comparing results to those obtained using lasso regression analysis. Signaling networks were constructed from the protein pairs that were significantly different in the t-test and lasso regression analysis. Predicted networks were also compared to known networks from public protein-protein interaction and signaling databases. By characterizing unique "protein signatures" through this rapid computational analysis, and placing them in the context of canonical biological networks, we identify signaling pathways distinct to subcategories of AML patients.
Authors:
Heather York; Steven M Kornblau; Amina Ann Qutub
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Proteomics     Volume:  12     ISSN:  1615-9861     ISO Abbreviation:  Proteomics     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-07-18     Completed Date:  2012-11-29     Revised Date:  2014-09-26    
Medline Journal Info:
Nlm Unique ID:  101092707     Medline TA:  Proteomics     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  2084-93     Citation Subset:  IM    
Copyright Information:
© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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MeSH Terms
Descriptor/Qualifier:
Chromosome Aberrations*
Cytogenetic Analysis / methods
Humans
Leukemia, Myeloid, Acute / genetics*,  metabolism
Oncogene Proteins, Fusion / genetics,  metabolism
Protein Array Analysis / methods*
Protein Interaction Mapping / methods
Protein Interaction Maps*
Proteins / genetics*,  metabolism*
Proteomics / methods*
Regression Analysis
Systems Biology / methods
Transcriptome / methods
Grant Support
ID/Acronym/Agency:
P30 CA016672/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Oncogene Proteins, Fusion; 0/Proteins; 0/inv(16) fusion protein, human

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