Analysis and modeling of time-course gene-expression profiles from nanomaterial-exposed primary human epidermal keratinocytes

Abstract Background Historical and updated information provided by time-course data collected during an entire treatment period proves to be more useful than information provided by single-point data. Accurate predictions made using time-course data on multiple biomarkers that indicate a patient’s response to therapy contribute positively to the decision-making process associated with designing effective treatment programs for various diseases. Therefore, the development of prediction methods incorporating time-course data on multiple markers is necessary. Results We proposed new methods that may be used for prediction and gene selection via time-course gene expression profiles. Our prediction method consolidated multiple probabilities calculated using gene expression profiles collected over a series of time points to predict therapy response. Using two data sets collected from patients with hepatitis C virus (HCV) infection and multiple sclerosis (MS), we performed numerical experiments that predicted response to therapy and evaluated their accuracies. Our methods were more accurate than conventional methods and successfully selected genes, the functions of which were associated with the pathology of HCV infection and MS. Conclusions The proposed method accurately predicted response to therapy using data at multiple time points. It showed higher accuracies at early time points compared to those of conventional methods. Furthermore, this method successfully selected genes that were directly associated with diseases.

Download Full-text

Inference of gene regulatory networks and compound mode of action from time course gene expression profiles

Bioinformatics ◽

10.1093/bioinformatics/btl003 ◽

2006 ◽

Vol 22 (7) ◽

pp. 815-822 ◽

Cited By ~ 254

Author(s):

M. Bansal ◽

G. D. Gatta ◽

D. di Bernardo

Keyword(s):

Gene Expression ◽

Gene Regulatory Networks ◽

Mode Of Action ◽

Regulatory Networks ◽

Time Course ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Gene Regulatory

Download Full-text

Prediction of Pharmacological and Xenobiotic Responses to Drugs Based on Time Course Gene Expression Profiles

PLoS ONE ◽

10.1371/journal.pone.0008126 ◽

2009 ◽

Vol 4 (12) ◽

pp. e8126 ◽

Cited By ~ 58

Author(s):

Tao Huang ◽

WeiRen Cui ◽

LeLe Hu ◽

KaiYan Feng ◽

Yi-Xue Li ◽

...

Keyword(s):

Gene Expression ◽

Time Course ◽

Expression Profiles ◽

Gene Expression Profiles

Download Full-text

Differential and Overlapping Effects of 20,23(OH)2D3 and 1,25(OH)2D3 on Gene Expression in Human Epidermal Keratinocytes: Identification of AhR as an Alternative Receptor for 20,23(OH)2D3

International Journal of Molecular Sciences ◽

10.3390/ijms19103072 ◽

2018 ◽

Vol 19 (10) ◽

pp. 3072 ◽

Cited By ~ 36

Author(s):

Andrzej Slominski ◽

Tae-Kang Kim ◽

Zorica Janjetovic ◽

Anna Brożyna ◽

Michal Żmijewski ◽

...

Keyword(s):

Gene Expression ◽

Molecular Modeling ◽

Vitamin D3 ◽

Expression Profiles ◽

Expression Patterns ◽

Canonical Pathway ◽

Epidermal Keratinocytes ◽

Hydroxyl Groups ◽

Dependent Manner ◽

Human Epidermal Keratinocytes

A novel pathway of vitamin D activation by CYP11A has previously been elucidated. To define the mechanism of action of its major dihydroxy-products, we tested the divergence and overlap between the gene expression profiles of human epidermal keratinocytes treated with either CYP11A1-derived 20,23(OH)2D3 or classical 1,25(OH)2D3. Both secosteroids have significant chemical similarity with the only differences being the positions of the hydroxyl groups. mRNA was isolated and examined by microarray analysis using Illumina’s HumanWG-6 chip/arrays and subsequent bioinformatics analyses. Marked differences in the up- and downregulated genes were observed between 1,25(OH)2D3- and 20,23(OH)2D3-treated cells. Hierarchical clustering identified both distinct, opposite and common (overlapping) gene expression patterns. CYP24A1 was a common gene strongly activated by both compounds, a finding confirmed by qPCR. Ingenuity pathway analysis identified VDR/RXR signaling as the top canonical pathway induced by 1,25(OH)2D3. In contrast, the top canonical pathway induced by 20,23(OH)2D3 was AhR, with VDR/RXR being the second nuclear receptor signaling pathway identified. QPCR analyses validated the former finding by revealing that 20,23(OH)2D3 stimulated CYP1A1 and CYP1B1 gene expression, effects located downstream of AhR. Similar stimulation was observed with 20(OH)D3, the precursor to 20,23(OH)2D3, as well as with its downstream metabolite, 17,20,23(OH)3D3. Using a Human AhR Reporter Assay System we showed marked activation of AhR activity by 20,23(OH)2D3, with weaker stimulation by 20(OH)D3. Finally, molecular modeling using an AhR LBD model predicted vitamin D3 hydroxyderivatives to be good ligands for this receptor. Thus, our microarray, qPCR, functional studies and molecular modeling indicate that AhR is the major receptor target for 20,23(OH)2D3, opening an exciting area of investigation on the interaction of different vitamin D3-hydroxyderivatives with AhR and the subsequent downstream activation of signal transduction pathways in a cell-type-dependent manner.

Download Full-text

CLUSTERING SAMPLES CHARACTERIZED BY TIME COURSE GENE EXPRESSION PROFILES USING THE MIXTURE OF STATE SPACE MODELS

Genome Informatics 2007 ◽

10.1142/9781860949920_0025 ◽

2007 ◽

Cited By ~ 1

Author(s):

OSAMU HIROSE ◽

RYO YOSHIDA ◽

RUI YAMAGUCHI ◽

SEIYA IMOTO ◽

TOMOYUKI HIGUCHI ◽

...

Keyword(s):

Gene Expression ◽

State Space ◽

Time Course ◽

Expression Profiles ◽

Gene Expression Profiles ◽

State Space Models

Download Full-text

Gene expression profiling of normal and malignant CD34-derived megakaryocytic cells

Blood ◽

10.1182/blood-2003-07-2597 ◽

2004 ◽

Vol 104 (10) ◽

pp. 3126-3135 ◽

Cited By ~ 52

Author(s):

Elena Tenedini ◽

Maria Elena Fagioli ◽

Nicola Vianelli ◽

Pier Luigi Tazzari ◽

Francesca Ricci ◽

...

Keyword(s):

Gene Expression ◽

Time Course ◽

Mitochondrial Permeability Transition ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Annexin V ◽

Permeability Transition Pore ◽

Permeability Transition ◽

Course Evaluation ◽

Oligonucleotide Microarray Analysis

Abstract Gene expression profiles of bone marrow (BM) CD34-derived megakaryocytic cells (MKs) were compared in patients with essential thrombocythemia (ET) and healthy subjects using oligonucleotide microarray analysis to identify differentially expressed genes and disease-specific transcripts. We found that proapoptotic genes such as BAX, BNIP3, and BNIP3L were down-regulated in ET MKs together with genes that are components of the mitochondrial permeability transition pore complex, a system with a pivotal role in apoptosis. Conversely, antiapoptotic genes such as IGF1-R and CFLAR were up-regulated in the malignant cells, as was the SDF1 gene, which favors cell survival. On the basis of the array results, we characterized apoptosis of normal and ET MKs by time-course evaluation of annexin-V and sub-G1 peak DNA stainings of immature and mature MKs after culture in serum-free medium with an optimal thrombopoietin concentration, and annexin-V–positive MKs only, with decreasing thrombopoietin concentrations. ET MKs were more resistant to apoptosis than their normal counterparts. We conclude that imbalance between proliferation and apoptosis seems to be an important step in malignant ET megakaryocytopoiesis.

Download Full-text