Project description:This cohort is an extension of our previous dataset (Spiers et al) containing DNA methylation profiled with the EPIC array on an additional 40 human fetal brain samples. Please note that these samples are from the same cohort as GSE58885.
Project description:Mutational burden and profiles to be studied in approx. 500 human primary melanomas with matched normal samples, part of the Leeds melanoma cohort. New custom design targeted capture panel covering melanoma-specific copy number alterations, promoter mutations, gene fusions, coding genes, HLA regions and IFNg/JAK/STAT pathway genes.
Project description:We investigated a cohort of 34 archival cutaneous melanoma samples by Agilent 40 kb-resolution CGH array. We found a non-random distribution of precise CNAs predictive for clinical outcome. Although most of the alterations defined in this study have been already reported, we mapped novel melanoma-specific CNAs at highest accuracy. Moreover, our data revealed distinct amplifications hotspots, some of which were validated by quantitative real-time PCR, enabling the identification of novel melanoma oncogenic candidates. Keywords: Cutaneous melanoma, Copy number alterations, Biomarkers, FFPE
Project description:In this manuscript, the authors had hypothesized a multi-dimensional approach modeling of both tumor and immune-related molecular mechanisms would better predict immune checkpoint blockade (ICB) response than simpler mutation-focused biomarkers, such as tumor mutational burden (TMB). The authors showed that the predictive power increases with deeper modeling of neoantigens and immune-related resistance mechanisms of ICB. The neoantigen burden score (NBS) and composite neoantigen presentation score (NEOPS) mentioned in the transcript was fully reproduced. Internally they used XGBoost algorithm to generate the results and the same is provided as dataset file. That is, the dataset provided here demonstrates that their integrative approach outperformed single-analyte biomarkers such as those found in cohort of patients with late-stage melanoma. This model is now addresses the issues in reproducing itself which was caused by version changes and deprecation of some R packages. It uses checkpoint package, which acts as a time machine for CRAN packages thereby promoting FAIReR sharing of ML models.
Project description:CTCF ChIP-seq of 39 primary samples derived from human acute leukemias, namely AML, T-ALL and mixed myeloid/lymphoid leukemias with CpG Island Methylator Phenotype (CIMP). Due to patient confidentiality considerations, the raw data files for this dataset have been deposited to the EGA controlled-access archive under the accession numbers EGAS00001007094 (study); EGAD00001011059 (dataset).
Project description:We have identified a gene encoding apolycomb-chromo domain binding protein. Complete knockout of these plants do not lead to a phenotype, but a reduction of gene expression in RNAi line produces a defined phenotype. This argues in favour of a compensation mechanism that is switched on once the concentration of the gene reaches a control level.The aim of the experiment is to search for such compensatory factors that are up-regulated in the knockout line. Experimenter name = Katharine Cain Experimenter phone = 01133433146 Experimenter department = University of Leeds Experimenter address = University of Leeds Experimenter address = Clarendon Way Experimenter address = Leeds Experimenter zip/postal_code = LS29JT Experimenter country = UK Keywords: genetic_modification_design
Project description:H3K27ac ChIP-seq of 79 primary samples derived from human acute leukemias, namely AML, T-ALL and mixed myeloid/lymphoid leukemias with CpG Island Methylator Phenotype (CIMP). In addition, 4 samples derived from CD34+ cord blood cells of healthy donors were included. Due to patient confidentiality considerations, the raw data files for this dataset have been deposited to the EGA controlled-access archive under the accession numbers EGAS00001007094 (study); EGAD00001011060 (dataset).
Project description:Embryonic genome activation (EGA) marks the onset of embryonic program and enables the transition toward the first lineage specification. However, the molecular features of EGA and the transcription factors (TFs) orchestrating this process remain unclear. Here, by performing single-cell RNA-seq on bovine embryos, we reveal that major EGA is asynchronously initiated among blastomeres at the 8-cell stage. Integrative analyses reveal distinctive protein accumulation compared to transcription and translation activation during bovine EGA. Furthermore, we investigate the role of SP1, a TF activated at the minor EGA stage, with motifs enriched in accessible chromatin during major EGA stage in bovine and human embryos. SP1 deficiency leads to morula arrest in bovine and impairs EGA in human embryos. Multi-omics analysis demonstrates that SP1 promotes early lineage gene expression by modulating nearby chromatin states in bovine and directly targets key EGA genes in human embryos. Together, our study delineates the dynamics of bovine EGA and uncovers the conserved and species-specific roles of SP1 in regulating EGA and early development in mammals.