Filtered selection coupled with support vector machines generate functionally relevant prediction model for colorectal cancer. In this study, we built a model that uses Support Vector Machine (SVM) to classify cancer and normal samples using Affymetrix exon microarray data obtained from 90 samples of 48 patients diagnosed with CRC. From the 22,011 genes, we selected the 20, 30, 50, 100, 200, 300 and 500 genes most relevant to CRC using the Minimum-RedundancyMaximum-Relevance (mRMR) technique. With these gene sets, an SVM model was designed using four different kernel types (linear, polynomial, radial basis function and sigmoid).
Filtered selection coupled with support vector machines generate a functionally relevant prediction model for colorectal cancer.
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Regulation of gene expression at the post-transcriptional level plays an indispensable role during TGFbeta-induced EMT and metastasis. This regulation involves a transcript-selective translational regulatory pathway in which a ribonucleoprotein (mRNP) complex, consisting of heterogeneous nuclear ribonucleoprotein E1 (hnRNP E1) and eukaryotic elongation factor 1A1 (eEF1A1), binds to a 3-UTR regulatory BAT (TGF activated translation) element and silences translation of Dab2 and ILEI mRNAs, two transcripts which are involved in mediating EMT. TGFbeta activates a kinase cascade terminating in the phosphorylation of hnRNP E1, by isoform-specific stimulation of protein kinase B/Akt2, inducing the release of the mRNP complex from the 3-UTR element, resulting in the reversal of translational silencing and increased expression of Dab2 and ILEI transcripts.
Establishment of a TGFβ-induced post-transcriptional EMT gene signature.
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Phosphate is essential for healthy bone growth and plays an essential role in fracture repair. Although phosphate deficiency has been shown to impair fracture healing, the mechanisms involved in impaired healing are unknown. More recently, studies have shown that the effect of phosphate deficiency on the repair process varied based on the genetic strain of mice, which is not characterized.
Hypophosphatemia Regulates Molecular Mechanisms of Circadian Rhythm.
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Timed sleep restriction designed to mimic human shift work was performed over a 2 week period in mice. On the final day, tissues were collected at 6 hour intervals to exmaine the effects of sleep restriction on circadian gene expression.
Circadian desynchrony promotes metabolic disruption in a mouse model of shiftwork.
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The molecular mechanisms by which individuals subjected to environmental heat stress either adapt or develop heat-related complications are not well understood. We analysed the changes in blood mononuclear gene expression patterns in human volunteers exposed to an extreme heat in a sauna (temperature of 78 6 C).
A Model of Exposure to Extreme Environmental Heat Uncovers the Human Transcriptome to Heat Stress.
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Mature B cells leave the bone marrow as naïve B cells and migrate to the secondary lymphoid organs where they encounter the antigen for the first time. This interaction stimulates B cells to rapidly grow and form characteristic histological structures called germinal center. In the germinal centers, B cells are targeted by mechanisms of genetic editing of the immunoglobulin loci, namely somatic hypermutation and class switch recombination, undergo selection for high affinity immunoglobulin receptors and are committed to differentiate into memory B cells or plasma cells. GCs display two histological areas the dark and the light zone that have been characterized as functionally distinct compartments through which B cells recycle multiple times during the germinal center reaction. Overall design: Naïve, germinal center and memory B cells were isolated from three independent donors each.
MEF2B Instructs Germinal Center Development and Acts as an Oncogene in B Cell Lymphomagenesis.
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The 24R,25-dihydroxyvitamin D metabolite (24R,25D) has long been suspected of participating to bone fracture repair. We used Cyp24a1-deficient mice, unable to produce 24R25D, to observe gene expression in callus tissue compared to that of control littermates.
Optimal bone fracture repair requires 24R,25-dihydroxyvitamin D3 and its effector molecule FAM57B2.
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Expression data from CD34+ hematopoietic cells transduced with control or anti-SLPI shRNA, serum starved and treated with G-CSF.
A lack of secretory leukocyte protease inhibitor (SLPI) causes defects in granulocytic differentiation.
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Somatic mutations of the MLL2 methyltransferase gene represent a common genetic lesion in multiple cancer types. In diffuse large B cell lymphoma (DLBCL) and follicular lymphoma (FL) (collectively, over 70% of all lymphoma diagnoses), these mutations are highly recurrent and appear early during transformation, possibly in pre-malignant precursors. Here we show that FL- and DLBCL-associated MLL2 mutations impair its enzymatic activity and lead to diminished global H3K4 methylation in normal germinal-center (GC) B cells and DLBCL, consistent with the enrichment of MLL2 binding at enhancer and promoter regions marked by mono- and tri-methylation. Conditional deletion of Mll2 early during B cell development, but not after initiation of the GC reaction, leads to increased percentages and numbers of GC B cells, which feature a distinct transcriptional profile defined by the enrichment of cell-cycle regulatory and B-cell receptor signaling genes. Consistently, Mll2-deficient B cells exhibit proliferative advantage and accumulation in the S phase of the cell cycle, which is influenced by the number of cell divisions. While GC-specific loss of Mll2 was not sufficient to initiate malignant transformation, compound Mll2-deficient/BCL2-transgenic mice displayed an increased incidence of clonal lymphoproliferations resembling the features of human FL and DLBCL. These findings suggest that early MLL2 loss favors BCL2-induced lymphomagenesis by remodeling the epigenetic landscape of the cancer precursor cells. Eradication of MLL2-deficient cells may represent a rational therapeutic approach targeting early tumorigenic events.
Disruption of KMT2D perturbs germinal center B cell development and promotes lymphomagenesis.
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