Molecular Classification of Crohn's Disease and Ulcerative Colitis Patients Using Transcriptional Profiles in Peripheral Blood Mononuclear Cells

Burczynski, Michael E.; Peterson, Ron L.; Twine, Natalie C.; Zuberek, Krystyna; Brodeur, Brendan J.; Casciotti, Lori; Maganti, Vasu; Reddy, Padma; Strahs, Andrew; Immermann, Fred; Spinelli, Walter; Schwertschlag, Ulrich; Slager, Anna M.; Cotreau, Monette M.; Dorner, Andrew J.

doi:10.2353/jmoldx.2006.050079

Cited by 211 publications

(160 citation statements)

References 24 publications

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“…Global gene expression profiling of peripheral blood cells has already proven to be a valuable tool not only for identifying novel clinically useful biomarkers, but also for determining pathogenic mechanisms in chronic inflammatory human diseases that provide new therapeutic targets (33,34). To our knowledge the current study is the first to apply this technology to study transcriptional patterns in unstimulated, unprimed PBN from chronic periodontitis patients.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, high-throughput gene expression approaches comparing peripheral blood cells from control subjects and patients have contributed to improved diagnostic procedures and molecular understanding for a range of chronic inflammatory diseases, such as systemic lupus erythematosus and ulcerative colitis (33,34). The aim of this study, therefore, was to use microarray technology to analyze the gene expression signature of hyperresponsive PBN from periodontitis patients to identify factors potentially important for disease pathogenesis.…”

Section: P Eripheral Blood Neutrophils (Pbn)mentioning

confidence: 99%

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Periodontitis Associates with a Type 1 IFN Signature in Peripheral Blood Neutrophils

Wright

Matthews

Chapple

et al. 2008

The Journal of Immunology

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Peripheral blood neutrophils from periodontitis patients exhibit a hyperreactive and hyperactive phenotype (collectively termed hyperresponsivity) in terms of production of reactive oxygen species (ROS). The molecular basis for this phenomenon, however, has yet to be determined. Our objectives were to identify genes differentially expressed in hyperresponsive peripheral blood neutrophils from chronic periodontitis patients relative to periodontally healthy controls and use these data to identify potential contributory pathways to the hyperresponsive neutrophil phenotype. Using microarray technology we demonstrated differential expression of 163 genes (149 increased, 14 decreased) representing a range of ontological classes. There was increased expression of a significant number of IFN-stimulated genes (ISG). RT-PCR analysis of ISG transcripts in individual and pooled samples further corroborated these data, and indicated that levels decreased to near those of controls following successful therapy. Significantly enhanced FcγR-stimulated ROS production was subsequently achieved by priming control neutrophils with IFN-α/-β/-γ, but not LPS, and gene expression analysis indicated that exposure to the type I IFN (in particular IFN-α) better replicated the mRNA profile observed in vivo. Further studies demonstrated that plasma levels of IFN-α were significantly higher in samples from patients relative to unaffected controls. Following successful periodontitis treatment, plasma IFN-α levels, neutrophil ISG expression, and FcγR-stimulated neutrophil ROS output of patients, all decreased to levels comparable with those of controls. In conclusion, although chronic periodontitis is a complex disease, raised IFN-α may be one determinant of the distinct molecular phenotype and hyperresponsivity exhibited by patients’ peripheral blood neutrophils.

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Section: Discussionmentioning

confidence: 99%

Section: P Eripheral Blood Neutrophils (Pbn)mentioning

confidence: 99%

Periodontitis Associates with a Type 1 IFN Signature in Peripheral Blood Neutrophils

Wright

Matthews

Chapple

et al. 2008

The Journal of Immunology

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“…Translocation occurs through a central channel and protruding on either side of this channel are the nuclear basket and cytoplasmic filaments, which serve as docking sites for many nucleocytoplasmic transport receptors and other regulatory proteins (9). NPCs are composed of more than 30 different proteins called nucleoporins (Nups), which are each present in from 8 to 32 copies per NPC (9). Many Nups contain phenylalanine-glycine (FG) repeat sequences.…”

Section: Overview Of Nucleocytoplasmic Transportmentioning

confidence: 99%

Nuclear localization signals and human disease

McLane

Corbett

2009

IUBMB Life

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SummaryIn eukaryotic cells, the physical separation of the genetic material in the nucleus from the translation and signaling machinery in the cytoplasm by the nuclear envelope creates a requirement for a mechanism through which macromolecules can enter or exit the nucleus as necessary. Nucleocytoplasmic transport involves the specific recognition of cargo molecules by transport receptors in one compartment followed by the physical relocation of that cargo into the other compartment through regulated pores that perforate the nuclear envelope. The recognition of protein cargoes by their transport receptors occurs via amino acid sequences in cargo proteins called nuclear targeting signals. Both nuclear import and export of proteins are highly regulated processes that control, not only what cargo can enter and/or exit the nucleus, but also when in the cell cycle and in what cell type, the cargo can be transported. Deregulation of the nuclear transport of specific cargoes has been linked to numerous cancers and developmental disorders highlighting the importance of understanding the mechanisms underlying nucleocytoplasmic transport and particularly the modulation of the specific interactions between transporter receptors and nuclear targeting signals within target cargo proteins.2009 IUBMB IUBMB Life, 61(7): [697][698][699][700][701][702][703][704][705][706] 2009

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“…We further demonstrate the application of our method on the IBD dataset (Burczynski et al, 2006). This dataset contains 22283 gene expres-sion levels from 127 people.…”

Section: A Real Data Examplementioning

confidence: 96%

Multiclass Sparse Discriminant Analysis

Zou

Mai²,

Yang

2018

STAT SINICA

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In recent years several sparse linear discriminant analysis methods have been proposed for high-dimensional classification and variable selection. However, most of these proposals focus on binary classification and they are not directly applicable to multiclass classification problems. Some sparse discriminant analysis methods that can handle multiclass classification problems, but their theoretical justifications remain unknown. In this paper, we propose a new multiclass sparse discriminant analysis method that estimates all discriminant directions simultaneously. We show that when applied to the binary case our proposal yields a classification direction that is equivalent to those by two successful binary sparse linear discriminant analysis methods in the literature. Thus, our proposal offers a neat unification of these seemingly unrelated proposals for binary sparse discriminant analysis. Our method can be solved by an efficient algorithm which is implemented in an open R package msda available from CRAN. We offer theoretical justification of our method by establishing a variable selection consistency result and rates of convergence under the ultrahigh dimensionality setting. We Statistica Sinica: Newly accepted Paper (accepted version subject to English editing) Multiclass Sparse Discriminant Analysis 2 further demonstrate the empirical performance of our method on simulated and real data.

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Molecular Classification of Crohn's Disease and Ulcerative Colitis Patients Using Transcriptional Profiles in Peripheral Blood Mononuclear Cells

Cited by 211 publications

References 24 publications

Periodontitis Associates with a Type 1 IFN Signature in Peripheral Blood Neutrophils

Periodontitis Associates with a Type 1 IFN Signature in Peripheral Blood Neutrophils

Nuclear localization signals and human disease

Multiclass Sparse Discriminant Analysis

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