10.7272/9P5D-Y278
Megan Laurance
Re-analysis of microarray data from rapamycin resistant DLBCL cell lines
University of California, San Francisco
2014
microarray
rapamycin
Diffuse Large B-Cell Lymphoma
pathway analysis
CD247
UCSF:CIND
UCSF
2013-10-22T18:45:09+00:00
Dataset
UCSF Datashare Data Use Agreement
This dataset contains a re-analysis of the raw microarray data originally
published by Petrich AM et al in 2012 (citation details are provided
through the link to the GEO record). We were interested in re-analyzing
the data because the list of differentially expressed genes that were
identified when comparing rapamycin resistant DLBCL cell lines to
rapamycin sensitive cell lines was not included in the original article or
supplemental materials. We were interested in validating and expanding
upon the findings from the original article by reevaluating the raw
microarray data. Our reanalysis identified over 200 genes that were
significantly differentially expressed between rapamycin resistant and
sensitive cells. Importantly, our analysis highlighted a gene that was
highly upregulated in rapamycin resistant cells, CD247, that was not the
focus on the original publication, and is the target of a drug currently
in clinical trials for refractory DLBCL. Our reanalysis also highlighted
the role of SYK, a kinase upregulated in rapamycin resistant cell lines,
that has a direct molecular relationship with CD247, and is a potential
biomarker of drug response in DLBCL.
The methods used to generate the original microarray data are described in
the GEO record where the data were originally published:
http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE27255 We downloaded
the raw Affymetrix data (CEL files) from GEO for renalysis. Statistical
and quality analysis was performed using the data analysis pipeline in
iReport (http://www.ingenuity.com/products/ireport) which utilizes
packages such as RMA and Limma from Bioconductor, in the R programming
language. A full description of the analysis packages used by this
pipeline are included in the word document "GSE27255 stats and QC
details" included in this DataShare record. Analysis of microarray
data in iReport identified 229 differentially expressed genes (DEGs) with
a p-value <0.05, fold change >1.5. These DEGs were then uploaded and
analyzed in Ingenuity Pathway Analysis (www.ingenuity.com) for functional
enrichment, pathway analysis, and drug target/biomarker analysis. Our
novel findings with respect to the role of CD247 and SYK in rapamycin
resistant DLBCL cell lines is depicted in the pathway image fine "Rap
resist network with CD247" which is included in this DataShare
record.
The original microarray data that was used for this reanalysis use case is
described in the GEO record GSE27255.
http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE27255