Project description:The aim of this work is to unveil the gene regulatory networks - crucial for the different stages of intracellular survival - in the bovine and zoonotic pathogen Brucella abortus.These data are part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/
Project description:Transcriptome studies in patients with rare genetic diseases can potentially aid in the interpretation of likely causal genetic variation through identification of altered transcript abundance and/or structure. RNA-Seq is the most sensitive assay for both investigating transcript structure and abundance. The primary aim of this pilot project is to investigate to what degree integrating exome-Seq and RNA-Seq data on the same individual can accelerate the identification of causal alleles for rare genetic diseases. There are two main strands to this: (i) identifying which variants discovered in exome-seq appear to be having a functional impact on transcripts, and (ii)identifying transcript outliers, especially among known causal genes, that may not necessarily have a causal variant identified from exome sequencing. The latter may identify the presence of causal variants that lie far from coding regions (e.g. the formation of cryptic splice sites deep within introns, or loss of long range regulatory elements), which can be confirmed with further targeted genetic assays. Just over 50% of all disease-causing variants recorded in theHuman Gene Mutation Database (HGMD) affect transcript structure and abundance (e.g.nonsense SNVs, essential splice site SNVs, frame shifting indels, CNVs).This pilot project will study RNA from lymphoblastoid cell-lines from 12 patients with primordial dwarfism syndromes, for 10 of these samples we have previously generate exome data as part of our collaboration with the group of Prof Andrew Jackson. The two remaining samples are positive controls where the causal mutation is known, and is known to affect transcript structure and/or abundance. Primordial dwarfism is a prime candidate for these RNA-seq studies because all known causal mutations to date have key roles in DNA replication and thus, unsurprisingly, the products of the causal genes are typically ubiquitously expressed. Each RNA will be sequenced, with two technical replicates (independent RT-PCR and libraries) per sample, and each replicate run in 1/2 of a HiSeq lane using 100bp paired reads. Samples preparation was as follows :The cells were grown to confluency, then pellets frozen at -80. RNA samples were prepared using the Qiagen RNeasy kit, then nanodropped and analyzed using the bioanalyzer to determine concentration and purity. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/
Project description:To investigate impacts of genome-wide loss of Cytosine methylation at CG sites (mCs) on global expression of protein-coding genes (henceforth referring to genes), we conducted deep RNA-seq analysis on OsMET1-2â/â relative to its sibling WT and heterozygote (OsMET1-2+/â), each with two biological replicates
Project description:To establish a systematic approach for the determination of human biological & disease relevance through the generation of epigenome data in cell types of interest. Integration of cell type epigenome data with existing & newly generated reference data from human tissue and cell types to identify assay systems which will provide greater confidence in translating target biology and compound pharmacology to patients. To provide a framework for the identification of optimal cell types for target identification/validation studies and drug discovery programs across multiple therapeutic areas. Development of bioinformatics pipelines and CTTV components for analysis and provision of data
Project description:Study to perform RNAseq on the Mtb ?esx3 and complemented control including the non-coding RNAs.These data are part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/
Project description:Tumor-derived cell lines have served as vital models to advance our understanding of oncogene function and therapeutic response1. Although substantial effort has been directed to defining the genomic constitution of cancer cell line panels24, the transcriptome which represents the active program of a cell remains understudied. Here, we describe RNA sequencing and SNP array analysis of 675 commonly used human cancer cell lines. We explore numerous transcriptome features including coding and non-coding gene expression, transcribed mutations, gene fusion and expression of non-human sequences. Aside from many known aberrations we find new surprising characteristics, including more than 2200 unique fusion gene pairs representing a vast, testable repertoire of oncogenic fusions, many of which have analogs found in primary human tumors. We show that a combination of multiple genome and transcriptome features in a novel pathway-based approach enhances prediction of response to various targeted therapeutics. Our results provide valuable new insights into these critical pre-clinical models and provide added context for interpreting the numerous studies that employ these widely used cell lines. The raw sequence files were submitted to the European Genome-Phenome Archive (EGA) under accession EGAS00001000610 ( https://www.ebi.ac.uk/ega/datasets/EGAD00001000725 ). Processed, human non-identifiable data, together with a README file describing the data (140625_Klijn_README.txt) are available here in E-MTAB-2706.additional.*.zip files: https://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-2706/files .
Project description:Gene transcription is an essential step of gene function and transcriptome variation is of agronomical, ecological and evolutionary importance. To explore global expression patterns and dissect the underlying genetic mechanisms are important scientific inquires which are still largely unknown, especially between a segregating population and the parents. In our study, we used RNA-Seq to profile the shoot apex transcriptome variation (including protein coding genes and non-coding genes) in maize IBM RIL population, to map eQTLs underlying the transcriptome variations and to utilize eQTLs to clone genes involved in maize shoot apices development. We revealed that: Much of the variation (the population mean, the coefficient of variation) of gene expression levels in RILs is reflective of differences present among the parents; These transcriptome variations could be explained by 30,774 eQTLs with 96 trans-eQTL hotspots; In many cases, the genes commonly regulated by a trans-eQTL hotspot are enriched for a specific function or act in the same genetic pathway; Structural variation within and near genes contributs to cis-regulatory variation. All of these results indicate Mendelian factors play as major contributors to the transcriptome variation. Meanwhile, non-Mendelian regulations were also observed as paramutation-like expression pattern for 145 genes, of which 88% genes were predicted to be potential targets of miRNAs or ta-siRNAs, and as unexpected presence/absence expression patterns for 210 genes. These genes with unexpected presence/absence expression patterns in the RILs likely include examples of functional genes as well as transposed gene fragments that may contribute to regulatory variation of their ancestral syntenic genes.