SNVMix: predicting single nucleotide variants from next-generation sequencing of tumors

Motivation: Next-generation sequencing (NGS) has enabled whole genome and transcriptome single nucleotide variant (SNV) discovery in cancer. NGS produces millions of short sequence reads that, once aligned to a reference genome sequence, can be interpreted for the presence of SNVs. Although tools exist for SNV discovery from NGS data, none are specifically suited to work with data from tumors, where altered ploidy and tumor cellularity impact the statistical expectations of SNV discovery

Histone H3 globular domain acetylation identifies a new class of enhancers

Histone acetylation is generally associated with active chromatin, but most studies have focused on the acetylation of histone tails. Various histone H3 and H4 tail acetylations mark the promoters of active genes. These modifications include acetylation of histone H3 at lysine 27 (H3K27ac), which blocks Polycomb-mediated trimethylation of H3K27 (H3K27me3). H3K27ac is also widely used to identify active enhancers, and the assumption has been that profiling H3K27ac is a comprehensive way of cataloguing the set of active enhancers in mammalian cell types. Here we show that acetylation of lysine residues in the globular domain of histone H3 (lysine 64 (H3K64ac) and lysine 122 (H3K122ac)) marks active gene promoters and also a subset of active enhancers. Moreover, we find a new class of active functional enhancers that is marked by H3K122ac but lacks H3K27ac. This work suggests that, to identify enhancers, a more comprehensive analysis of histone acetylation is required than has previously been considered

Priority questions to shape the marine and coastal policy research agenda in the United Kingdom

United Kingdom (UK) and European Union policy is rapidly developing to meet international targets for the sustainable use and protection of the marine environment. To inform this process, research needs to keep pace with these changes and research questions must be focused on providing robust scientific evidence. Thirty four priority research questions within six broad themes were identified by delegates who attended the 1st marine and coastal policy Forum, hosted by the Centre for Marine and Coastal Policy Research at Plymouth University in June 2011. The priority questions formed through this research are timely and reflect the pace and change of marine policy in the UK in response to international, European and national policy drivers. Within the data theme, the majority of questions seek to find improved procedures to manage and use data effectively. Questions related to governance focus on how existing policies should be implemented. The marine conservation questions focus entirely upon implementation and monitoring of existing policy. Questions related to ecosystem services focus on research to support the conceptual links between ecosystem services, ecosystem function, and marine management. Questions relating to marine citizenship are fundamental questions about the nature of societal engagement with the sea. Finally, the marine planning questions focus upon understanding the general approaches to be taken to marine planning rather than its detailed implementation. The questions that have emerged from this process vary in scale, approach and focus. They identify the interdisciplinary science that is currently needed to enable the UK to work towards delivering its European and international commitments to achieve the sustainable use and protection of the marine environment

MHC class II transactivator CIITA is a recurrent gene fusion partner in lymphoid cancers

Chromosomal translocations are critically involved in the molecular pathogenesis of B-cell lymphomas, and highly recurrent and specific rearrangements have defined distinct molecular subtypes linked to unique clinicopathological features(1,2). In contrast, several well-characterized lymphoma entities still lack disease-defining translocation events. To identify novel fusion transcripts resulting from translocations, we investigated two Hodgkin lymphoma cell lines by whole-transcriptome paired-end sequencing (RNA-seq). Here we show a highly expressed gene fusion involving the major histocompatibility complex (MHC) class II transactivator CIITA (MHC2TA) in KM-H2 cells. In a subsequent evaluation of 263 B-cell lymphomas, we also demonstrate that genomic CIITA breaks are highly recurrent in primary mediastinal B-cell lymphoma (38%) and classical Hodgkin lymphoma (cHL) (15%). Furthermore, we find that CIITA is a promiscuous partner of various in-frame gene fusions, and we report that CIITA gene alterations impact survival in primary mediastinal B-cell lymphoma (PMBCL). As functional consequences of CIITA gene fusions, we identify downregulation of surface HLA class II expression and overexpression of ligands of the receptor molecule programmed cell death 1 (CD274/PDL1 and CD273/PDL2). These receptor–ligand interactions have been shown to impact anti-tumour immune responses in several cancers(3), whereas decreased MHC class II expression has been linked to reduced tumour cell immunogenicity(4). Thus, our findings suggest that recurrent rearrangements of CIITA may represent a novel genetic mechanism underlying tumour–microenvironment interactions across a spectrum of lymphoid cancers