Project description:Genome-wide DNA methylation profiling of 251 whole-blood samples from children aged 2 years from the ENID mother-child cohort in The Gambia.
Project description:To gain holistic of the immune landscape of lesions following infection with Mycobacterium tuberculosis, we aerosol infected C3HeB/FeJ mice with 1-3 CFU of Mtb (SA161 strain). 35 days following infection, lungs were harvested and fixed, then embedded and frozed in OCT. 10um sections were obtained, classified as necrotic or non-necrotic by visual inspection and brightfield imaging, then stained with markers delineating lesions, and subsequently processed and sampled using the nanostring GeoMX platform. We then compared the transcriptional environment of necrotic vs non-necrotic lesions
Project description:Genome wide DNA methylation profiling in infant's blood from a mother/child cohort in The Gambia. The main variables of the analyses were the intra-uterine exposure to aflatoxin B1 (AFB1) and the season of conception. The Illumina Infinium HumanMethylation 450k Beadchip was used to obtain DNA methylation profiles across approximately 450,000 CpGs in whole peripheral blood obtained at 3-6 months of age. A total of 124 samples were analysed, including 3 technical replicates.
Project description:Genome-wide expression data can provide important insights into normal and pathological cellular processes. However, the ability to use gene expression data to quantitatively assess the activation state of a given signaling pathway or transcriptional network in a sensitive and specific manner remains an important unmet goal. We now describe a computational algorithm, energy-paired scoring (EPS), that satisfies these criteria by predicting pathway activity using gene-gene interactions within a pathway signature in a manner analogous to the estimation of energy generated by two charged particles, as described by Coulomb’s law. We demonstrate the ability of EPS to: quantitatively assess pathway activation levels in vivo and in vitro; accurately estimate the extent of pathway inhibition achieved by gene knockdown; sensitively detect crosstalk between endogenous signaling pathways in vivo; and accurately identify compounds capable of inhibiting selected signaling pathways. Our findings indicate that EPS can accurately predict pathway activity over a wide dynamic range based upon gene expression data sets derived from multiple profiling platforms, as well as different species, tissues and cell types in both in vitro and in vivo contexts Four timepoints (0h, 24h, 48h and 96h) with 3 replicates per timepoint of doxycycline induction for MTB (Control), MTB/TAN, MTB/TOM and MTB/TWNT1
Project description:Genome wide DNA methylation profiling in infant's blood from a mother/child cohort in The Gambia. The main variables of the analyses were the intra-uterine exposure to aflatoxin B1 (AFB1) and the season of conception. The Illumina Infinium HumanMethylation 450k Beadchip was used to obtain DNA methylation profiles across approximately 450,000 CpGs in whole peripheral blood obtained at 3-6 months of age. A total of 124 samples were analysed, including 3 technical replicates. Bisulphite converted DNA from the 124 samples were hybridised to the Illumina Infinium HumanMethylation 450k Beadchip