graphite - a Bioconductor package to convert pathway topology to gene network

Sales, Gabriele; Calura, Enrica; Cavalieri, Duccio; Romualdi, Chiara

doi:10.1186/1471-2105-13-20

Cited by 182 publications

(173 citation statements)

References 33 publications

Supporting

Mentioning

173

Contrasting

Order By: Relevance

“…Genes with a q-value < 0.05 were considered significantly differentially expressed and were included in the downstream pathway analysis. Signaling Pathway Impact Analysis was conducted using the Bioconductor packages SPIA and Graphite, using the differentially expressed gene list and their log2 fold changes as input 34, 35 . Pathway databases included in the analysis include KEGG, Biocarta, NCI and Reactome.…”

Section: Methodsmentioning

confidence: 99%

Dysregulated circadian rhythm pathway in human osteoarthritis: NR1D1 and BMAL1 suppression alters TGF-β signaling in chondrocytes

Akagi

Akatsu

Fisch

et al. 2017

Osteoarthritis and Cartilage

View full text Add to dashboard Cite

Objectives Circadian rhythm (CR) was identified by RNA sequencing as the most dysregulated pathway in human osteoarthritis (OA) in articular cartilage. This study examined circadian rhythmicity in cultured chondrocytes and the role of the CR genes NR1D1 and BMAL1 in regulating chondrocyte functions. Methods RNA was extracted from normal and OA-affected human knee cartilage (n=14 each). Expression levels of NR1D1 and BMAL1 mRNA and protein were assessed by quantitative PCR and immunohistochemistry. Human chondrocytes were synchronized and harvested at regular intervals to examine circadian rhythmicity in RNA and protein expression. Chondrocytes were treated with small interfering RNA (siRNA) for NR1D1 or BMAL1, followed by RNA sequencing and analysis of the effects on the TGF-β pathway. Results NR1D1 and BMAL1 mRNA and protein levels were significantly reduced in OA compared to normal cartilage. In cultured human chondrocytes, a clear circadian rhythmicity was observed for NR1D1 and BMAL1. Increased BMAL1 expression was observed after knocking down NR1D1, and decreased NR1D1 levels were observed after knocking down BMAL1. Sequencing of RNA from chondrocytes treated with NR1D1 or BMAL1 siRNA identified 330 and 68 significantly different genes, respectively, and this predominantly affected the TGF-β signaling pathway. Conclusions The circadian rhythm pathway is dysregulated in OA cartilage. Interference with circadian rhythmicity in cultured chondrocytes affects TGF-β signaling, which is a central pathway in cartilage homeostasis.

show abstract

Section: Methodsmentioning

confidence: 99%

Dysregulated circadian rhythm pathway in human osteoarthritis: NR1D1 and BMAL1 suppression alters TGF-β signaling in chondrocytes

Akagi

Akatsu

Fisch

et al. 2017

Osteoarthritis and Cartilage

View full text Add to dashboard Cite

show abstract

“…Pathway maps were obtained from the KEGG database (Kanehisa et al, 2014) and exported as R objects into the package graphite (Sales et al, 2012). For the GSA, fold-changes were used as gene-level statistics, and the mean was used as the geneset enrichment score.…”

Section: Gene-set Analysis (Gsa) Of Transcriptomics Datamentioning

confidence: 99%

3-D nasal cultures: Systems toxicological assessment of a candidate modified-risk tobacco product

Iskandar

Mathis

Martin

et al. 2017

ALTEX

View full text Add to dashboard Cite

ratory animals -to reduce the number of animals, to refine the design of procedures such that pain and distress are minimized, and to replace animal models with alternative methods and lower organisms when possible (Doke and Dhawale, 2015). In this regard, the capability to preserve human respiratory cells in culture provides a tool not only to generate mechanistic data, but also to improve the predicted effects of exposure hazard through inhalation in humans. An emphasis on assessment studies using human-derived in vitro culture systems will reduce the problems that are inherent to interspecies translatability (Manuppello and Sullivan, 2015).In vitro toxicology approaches have evolved from focusing on the molecular changes within a cell to understanding the toxicity-related mechanisms (cell-cell interactions) in models IntroductionMechanistic investigation of the impact of exposure on the lower airway remains challenging because access to lung tissues is limited. Although biopsy samples can be obtained from patients/donors for mechanistic studies of exposure-induced injury, a biopsy procedure is invasive and there are related ethical concerns (Peppercorn, 2013). Alternatively, animal studies allow the collection of biological samples from various animal models of human diseases. However, biological responses can vary among animal species, and findings obtained from animal studies may not apply to humans. Alternatives to animal testing have been proposed to overcome these drawbacks, including the 3Rs strategy -reduction, refinement, and replacement of labo- Research SummaryIn vitro toxicology approaches have evolved from a focus on molecular changes within a cell to understanding of toxicity-related mechanisms in systems that can mimic the in vivo environment. The recent development of three dimensional (3-D) organotypic nasal epithelial culture models offers a physiologically robust system for studying the effects of exposure through inhalation. Exposure to cigarette smoke (CS) is associated with nasal inflammation; thus, the nasal epithelium is relevant for evaluating the pathophysiological impact of CS exposure. The present study investigated further the application of in vitro human 3-D nasal epithelial culture models for toxicological assessment of inhalation exposure. Aligned with 3Rs strategy, this study aimed to explore the relevance of a human 3-D nasal culture model to assess the toxicological impact of aerosols generated from a candidate modified risk tobacco product (cMRTP), the Tobacco Heating System (THS) 2.2, as compared with smoke generated from reference cigarette 3R4F. A series of experimental repetitions, where multiple concentrations of THS2.2 aerosol and 3R4F smoke were applied, were conducted to obtain reproducible measurements to understand the cellular/molecular changes that occur following exposure. In agreement with "Toxicity Testing in the 21 st Century -a Vision and a Strategy", this study implemented a systems toxicology approach and found that for all tested concentrations the impa...

show abstract

“…into a graphical structure in which a node represents a simple element like a gene/protein (14). In fact, whereas pathway nodes might consist of multiple entities such as protein complexes, gene family members and chemical compounds, microarrays measure each single element of complexes and gene family separately.…”

Section: Methodsmentioning

confidence: 99%

“…In fact, whereas pathway nodes might consist of multiple entities such as protein complexes, gene family members and chemical compounds, microarrays measure each single element of complexes and gene family separately. Here, we used 14), a Bioconductor package addressing these issues. In general, takes pathway information from four different databases (Biocarta; KEGG, (15); NCI/Nature Pathway Interaction Database, (16); Reactome, (17)) and this information is interpreted and opportunely coded by following specific biologically driven rules.…”

Section: Methodsmentioning

confidence: 99%

Along signal paths: an empirical gene set approach exploiting pathway topology

Martini

Sales

Massa

et al. 2012

Nucleic Acids Research

Self Cite

108

130

View full text Add to dashboard Cite

Gene set analysis using biological pathways has become a widely used statistical approach for gene expression analysis. A biological pathway can be represented through a graph where genes and their interactions are, respectively, nodes and edges of the graph. From a biological point of view only some portions of a pathway are expected to be altered; however, few methods using pathway topology have been proposed and none of them tries to identify the signal paths, within a pathway, mostly involved in the biological problem. Here, we present a novel algorithm for pathway analysis , that tries to fill in this gap. implements a two-step empirical approach based on the exploitation of graph decomposition into a junction tree to reconstruct the most relevant signal path. In the first step selects significant pathways according to statistical tests on the means and the concentration matrices of the graphs derived from pathway topologies. Then, it identifies within these pathways the signal paths having the greatest association with a specific phenotype. We test our approach on simulated and two real expression datasets. Our results demonstrate the efficacy of in the identification of signal transduction paths totally coherent with the biological problem.

show abstract

graphite - a Bioconductor package to convert pathway topology to gene network

Cited by 182 publications

References 33 publications

Dysregulated circadian rhythm pathway in human osteoarthritis: NR1D1 and BMAL1 suppression alters TGF-β signaling in chondrocytes

Dysregulated circadian rhythm pathway in human osteoarthritis: NR1D1 and BMAL1 suppression alters TGF-β signaling in chondrocytes

3-D nasal cultures: Systems toxicological assessment of a candidate modified-risk tobacco product

Along signal paths: an empirical gene set approach exploiting pathway topology

Contact Info

Product

Resources

About