Variable slope normalization of reverse phase protein arrays

Neeley, E. Shannon; Kornblau, Steven M.; Coombes, Kevin R.; Baggerly, Keith A.

doi:10.1093/bioinformatics/btp174

Cited by 77 publications

(74 citation statements)

References 32 publications

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“…34 The loading control 35 and topographical normalization procedures accounted for variations in protein concentrations and background staining. Normalization procedures were performed using the R software program (Version 2.…”

Section: Discussionmentioning

confidence: 99%

Survivin is highly expressed in CD34+38− leukemic stem/progenitor cells and predicts poor clinical outcomes in AML

Carter

Qiu

Huang

et al. 2012

Blood

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Survivin, a member of the inhibitors of apoptosis protein family, plays important roles in cell proliferation and survival and is highly expressed in various malignancies, including leukemias. To better understand its role in acute myeloid leukemia (AML), we profiled survivin expression in samples obtained from 511 newly diagnosed AML patients and in CD34 ؉ 38 ؊ AML stem/progenitor cells using a validated reverse-phase protein array; we correlated its levels with clinical outcomes and with levels of other proteins in the same sample set. We found that survivin levels were higher in bone marrow than in paired peripheral blood leukemic cells (n ‫؍‬ 140, P ‫؍‬ .0001) and that higher survivin levels significantly predicted shorter overall (P ‫؍‬ .016) and event-free (P ‫؍‬ .023) survival in multivariate Cox model analysis. Importantly, survivin levels were significantly higher in CD34 ؉ 38 ؊ AML stem/progenitor cells than in bulk blasts and total CD34 ؉ AML cells (P < .05).

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Section: Discussionmentioning

confidence: 99%

Survivin is highly expressed in CD34+38− leukemic stem/progenitor cells and predicts poor clinical outcomes in AML

Carter

Qiu

Huang

et al. 2012

Blood

Self Cite

View full text Add to dashboard Cite

show abstract

“…36 Loading control 37 and topographical normalization procedures accounted for protein concentration and background staining variations. Analysis using unbiased clustering and perturbation bootstrap clustering, and principle component analysis was then performed as described previously.…”

Section: Discussionmentioning

confidence: 99%

Abnormal expression of FLI1 protein is an adverse prognostic factor in acute myeloid leukemia

Kornblau¹,

Qiu²,

Zhang

et al. 2011

Blood

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Friend leukemia virus integration 1 (FLI1), an Ets transcription factor family member, is linked to acute myelogenous leukemia (AML) by chromosomal events at the FLI1 locus, but the biologic impact of FLI1 expression on AML is unknown. FLI1 protein expression was measured in 511 newly diagnosed AML patients. Expression was similar in peripheral blood (PB) and BM and higher at diagnosis than at relapse (P ‫؍‬ .02). Compared with normal CD34 ؉ cells, expression in AML was above or below normal in 32% and 5% of patients, respectively. Levels were negatively correlated with an antecedent hematologic disorder (P ‫؍‬ .002) but not with age or cytogenetics. Mutated NPM1 (P ‫؍‬ .0007) or FLT3-ITD (P < .02) had higher expression.

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“…Neely et al (Neeley et al, 2009) processed clinically similar ALL samples in two batches and observed differences in their protein data distributions. There were additive and multiplicative effects in the data that could not be accounted by biological or sample loading differences.…”

Section: Star*methodsmentioning

confidence: 99%

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

Campbell¹,

Yau²,

Bowlby³

et al. 2018

Cell Reports

267

303

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SUMMARY This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smoking and/or human papillomavirus (HPV). SCCs harbor 3q, 5p, and other recurrent chromosomal copy-number alterations (CNAs), DNA mutations, and/or aberrant methylation of genes and microRNAs, which are correlated with the expression of multi-gene programs linked to squamous cell stemness, epithelial-to-mesenchymal differentiation, growth, genomic integrity, oxidative damage, death, and inflammation. Low-CNA SCCs tended to be HPV(+) and display hypermethylation with repression of TET1 demethylase and FANCF, previously linked to predisposition to SCC, or harbor mutations affecting CASP8, RAS-MAPK pathways, chromatin modifiers, and immunoregulatory molecules. We uncovered hypomethylation of the alternative promoter that drives expression of the ΔNp63 oncogene and embedded miR944. Co-expression of immune checkpoint, T-regulatory, and Myeloid suppressor cells signatures may explain reduced efficacy of immune therapy. These findings support possibilities for molecular classification and therapeutic approaches.

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Variable slope normalization of reverse phase protein arrays

Abstract: Code to implement the method in the statistical package R and anonymized data are available at (http://bioinformatics.mdanderson.org/supplements.html).

Cited by 77 publications

References 32 publications

Survivin is highly expressed in CD34+38− leukemic stem/progenitor cells and predicts poor clinical outcomes in AML

Survivin is highly expressed in CD34+38− leukemic stem/progenitor cells and predicts poor clinical outcomes in AML

Abnormal expression of FLI1 protein is an adverse prognostic factor in acute myeloid leukemia

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

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