Internal standard-based analysis of microarray data. Part 1: analysis of differential gene expressions

Dozmorov, Igor; Lefkovits, Ivan

doi:10.1093/nar/gkp706

Cited by 36 publications

(59 citation statements)

References 38 publications

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“…BMDCs were stimulated with LPS or poly(I:C) for 3 h. RNA was extracted by using the miRNeasy kit (Qiagen). Methods for data normalization and analysis are based on the use of "internal standards" (35)(36)(37), which was slightly modified to the needs of RNA sequencing data analysis. Functional analysis of identified genes was performed with Ingenuity Pathway Analysis (IPA; Ingenuity Systems).…”

Section: Methodsmentioning

confidence: 99%

Differential outcome of TRIF-mediated signaling in TLR4 and TLR3 induced DC maturation

Jain

Gao

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Recognition of pathogen-associated molecular patterns by Tolllike receptors (TLRs) on dendritic cells (DCs) leads to DC maturation, a process involving up-regulation of MHC and costimulatory molecules and secretion of proinflammatory cytokines. All TLRs except TLR3 achieve these outcomes by using the signaling adaptor myeloid differentiation factor 88. TLR4 and TLR3 can both use the Toll-IL-1 receptor domain-containing adaptor inducing IFN-β (TRIF)-dependent signaling pathway leading to IFN regulatory factor 3 (IRF3) activation and induction of IFN-β and -α4. The TRIF signaling pathway, downstream of both of these TLRs, also leads to DC maturation, and it has been proposed that the type I IFNs act in cis to induce DC maturation and subsequent effects on adaptive immunity. The present study was designed to understand the molecular mechanisms of TRIF-mediated DC maturation. We have discovered that TLR4-TRIF-induced DC maturation was independent of both IRF3 and type I IFNs. In contrast, TLR3-mediated DC maturation was completely dependent on type I IFN feedback. We found that differential activation of mitogen-activated protein kinases by the TLR4-and TLR3-TRIF axes determined the type I IFN dependency for DC maturation. In addition, we found that the adjuvanticity of LPS to induce T-cell activation is completely independent of type I IFNs. The important distinction between the TRIF-mediated signaling pathways of TLR4 and TLR3 discovered here could have a major impact in the design of future adjuvants that target this pathway.

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Section: Methodsmentioning

confidence: 99%

Differential outcome of TRIF-mediated signaling in TLR4 and TLR3 induced DC maturation

Jain

Gao

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…Methods for data normalization and analysis are based on the use of "internal standards" 61 that characterize some aspects of the system's behavior, such as technical variability, as presented elsewhere 62,63 . Genes with log 2 (fold change) > 2, P < 0.05 and RPKM > 0.5 were deemed to be significantly differentially expressed between the two conditions, and used for pathway analysis and upstream transcription factor analysis.…”

Section: Competing Financial Interestsmentioning

confidence: 99%

Fasting selectively blocks development of acute lymphoblastic leukemia via leptin-receptor upregulation

Xie

et al. 2016

Nat Med

121

114

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Dietary restriction, including fasting, delays aging and has pro-longevity effects in a wide range of organisms, and so has been considered for cancer prevention and the treatment of certain solid tumor types [1][2][3][4][5][6] . Fasting can promote hematopoietic stem cell-based regeneration and reverse immunosuppression [7][8][9] , and has been reported to promote the anti-cancer effects of chemotherapy 5,10 . However, the responsiveness of hematopoietic malignancies to dietary restriction, including fasting, remains unknown.AML is the most common form of adult acute leukemia, whereas ALL is the most common form of cancer in children; ALL also occurs in adults [11][12][13] . Although treatment of pediatric ALL is highly effective, a sizeable number of patients are nonresponders who succumb to this disease. The outcome of ALL in adults is substantially worse than for pediatric ALL, with a 5-year survival rate of approximately 40% 12 . Additionally, some types of ALL have a much poorer prognosis than others 12 . New therapeutic targets and approaches need to be identified to treat these leukemias more effectively. Here we investigated whether and how fasting regulates the development of B-ALL, T-ALL and AML. RESULTSFasting selectively inhibits the development of ALL but not AML To extend our previous work on the extrinsic and metabolic regulation of hematopoietic stem cells and cancer development 14-22 , we studied the effects of fasting on leukemia development. Mice from several retrovirus transplantation acute leukemia models, including the N-Myc B-ALL model 23 , the activated Notch1 T-ALL model 24 and the MLL-AF9 AML model 25,26 , were placed on various dietary regimens. Strikingly, a regimen consisting of six cycles of 1 d of fasting, followed by 1 d of feeding, implemented 2 d after transplantation (Fig. 1a) completely inhibited B-ALL development. The fasted mice had 32.85 ± 5.16, 11.31 ± 5.42 and 0.48 ± 0.12% of leukemic GFP + cells in peripheral blood (PB) at 3, 5 and 7 weeks post-transplantation, respectively, as compared to 49.52 ± 5.75, 56.27 ± 9.36 and 67.68 ± 8.39% of GFP + cells of the control mice (Fig. 1b,c). Concordantly, the percentages of leukemic cells in the bone marrow (BM) and spleen (SP) and the numbers of white blood cells (WBCs) in PB were also dramatically lower in the fasted mice at 7 weeks posttransplantation (Fig. 1c,d).Next, we measured the distribution of B lymphoblastic cells and myeloid cells in the GFP + compartment of the B-ALL mice. Control mice with B-ALL had 65-80% of B220 + cells (pan B lineage marker) and 0.5-2% of Mac-1 + cells (myeloid lineage marker) in GFP + fractions of PB, BM and SP (Fig. 1e,f), indicative of fully developed B-ALL. By contrast, there were only 19-28% of B220 + cells and 5-12% of Mac-1 + in GFP + fractions in fasted mice (Fig. 1e,f), consistent with loss of the B-ALL phenotype. There was also a higher percentage of New therapeutic approaches are needed to treat leukemia effectively. Dietary restriction regimens, including fasting, have been considered ...

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“…The relative level of methylation for each CG site was calculated as the ratio of methylated-probe signal to total locus signal intensity and defined within 0 to 1 range, exported from the Illumina BeadStudio software package. The data were then normalized as described previously, 22,23 using the variability of areas with low methylation level as a reference point. In order to find genes with methylation levels above the level of technical noise, a frequency histogram of raw methylation signal was determined for each array.…”

confidence: 99%

“…All methods and analyses were performed in Matlab (Mathworks, Natick, MA), unless otherwise specified. To identify differentially methylated CG sites between lupus patients and controls, we used the associative analysis as described by Dozmorov et al 23 CG sites with methylation signal greater than 6 SD above noise level and have at least 1.2-fold difference Table 5. Main functional annotations overrepresented by protein-protein interaction network (shown in Fig.…”

Section: O N O T D I S T R I B U T Ementioning

confidence: 99%

Genome-wide DNA methylation patterns in CD4+ T cells from patients with systemic lupus erythematosus

et al. 2011

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Internal standard-based analysis of microarray data. Part 1: analysis of differential gene expressions

Cited by 36 publications

References 38 publications

Differential outcome of TRIF-mediated signaling in TLR4 and TLR3 induced DC maturation

Differential outcome of TRIF-mediated signaling in TLR4 and TLR3 induced DC maturation

Fasting selectively blocks development of acute lymphoblastic leukemia via leptin-receptor upregulation

Genome-wide DNA methylation patterns in CD4+ T cells from patients with systemic lupus erythematosus

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