A library of gene expression signatures to illuminate normal and pathological lymphoid biology

Metabolism Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
Immunological Reviews (Impact Factor: 10.12). 05/2006; 210(1):67-85. DOI: 10.1111/j.0105-2896.2006.00373.x
Source: PubMed

ABSTRACT Genomics has provided a lever to pry open lymphoid cells and examine their regulatory biology. The large body of available gene expression data has also allowed us to define the of coordinately expressed genes, termed gene expression signatures, which characterize the states of cellular physiology that reflect cellular differentiation, activation of signaling pathways, and the action of transcription factors. Gene expression signatures that reflect the action of individual transcription factors can be defined by perturbing transcription factor function using RNA interference (RNAi), small-molecule inhibition, and dominant-negative approaches. We have used this methodology to define gene expression signatures of various transcription factors controlling B-cell differentiation and activation, including BCL-6, B lymphocyte-induced maturation protein-1 (Blimp-1), X-box binding protein-1 (XBP1), nuclear factor-kappaB (NF-kappaB), and c-myc. We have also curated a wide variety of gene expression signatures from the literature and assembled these into a signature database. Statistical methods can define whether any signature in this database is differentially expressed in independent biological samples, an approach we have used to gain mechanistic insights into the origin and clinical behavior of B-cell lymphomas. We also discuss the use of genomic-scale RNAi libraries to identify genes and pathways that may serve as therapeutic targets in B-cell malignancies.

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Available from: Lloyd T Lam, Sep 26, 2015
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    • "MM tumor profiles from patients enrolled on the APEX Study 039 of BTZ were obtained from NCBI Gene Expression Omnibus (GEO; GSE9782; Mulligan et al., 2007). Three Xbp1 signature gene sets were used: XBP1_Staudt_SigDB reflects Xbp1 overexpression in B cells (Shaffer et al., 2006) and together with other lymphoid transcription factor signatures was obtained from http://; V$XBP1_01 represents genes with promoters containing a conserved Xbp1 motif and is from the Broad MSigDB at; XBP1_MM and the related Ire1 signature, IRE1_MM, were generated by shRNA knockdown of Xbp1 or Ire1 in MM cells. "
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    Cancer cell 09/2013; 24(3):289-304. DOI:10.1016/j.ccr.2013.08.009 · 23.52 Impact Factor
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    • "An alternative approach is to generate signatures that reflect a specific biological process or outcome [9-11] or sets of coexpressed genes based upon correlation matrices [12-14]. One issue complicating analysis of any cancer gene expression data is the heterogeneity of samples. "
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    BMC Genomics 07/2013; 14(1):469. DOI:10.1186/1471-2164-14-469 · 3.99 Impact Factor
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    • "Although relatively modest, this level of enrichment is highly statistically significant (P = <0.0001 by Chi-square test). It should also be born in mind that the full set of genes that is repressed by BLIMP1 in plasma cells is likely to far exceed the 64 genes that have been experimentally validated in earlier studies [37], [41]. "
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