Pharmacogenomic testing in paediatrics: Clinical implementation strategies.

Pharmacogenomics (PGx) relates to the study of genetic factors determining variability in drug response. Implementing PGx testing in paediatric patients can enhance drug safety, helping to improve drug efficacy or reduce the risk of toxicity. Despite its clinical relevance, the implementation of PGx testing in paediatric practice to date has been variable and limited.

Automated PDF highlighting to support faster curation of literature for Parkinson's and Alzheimer's disease.

Unlabelled: Neurodegenerative disorders such as Parkinson's and Alzheimer's disease are devastating and costly illnesses, a source of major global burden. In order to provide successful interventions for patients and reduce costs, both causes and pathological processes need to be understood. The ApiNATOMY project aims to contribute to our understanding of neurodegenerative disorders by manually curating and abstracting data from the vast body of literature amassed on these illnesses.

Characterisation of mental health conditions in social media using Informed Deep Learning.

The number of people affected by mental illness is on the increase and with it the burden on health and social care use, as well as the loss of both productivity and quality-adjusted life-years. Natural language processing of electronic health records is increasingly used to study mental health conditions and risk behaviours on a large scale. However, narrative notes written by clinicians do not capture first-hand the patients' own experiences, and only record cross-sectional, professional impressions at the point of care.

Analysis of diagnoses extracted from electronic health records in a large mental health case register.

The UK government has recently recognised the need to improve mental health services in the country. Electronic health records provide a rich source of patient data which could help policymakers to better understand needs of the service users. The main objective of this study is to unveil statistics of diagnoses recorded in the Case Register of the South London and Maudsley NHS Foundation Trust, one of the largest mental health providers in the UK and Europe serving a source population of over 1.

An interactive genome browser of association results from the UK10K cohorts project.

Unlabelled: High-throughput sequencing technologies survey genetic variation at genome scale and are increasingly used to study the contribution of rare and low-frequency genetic variants to human traits. As part of the Cohorts arm of the UK10K project, genetic variants called from low-read depth (average 7×) whole genome sequencing of 3621 cohort individuals were analysed for statistical associations with 64 different phenotypic traits of biomedical importance. Here, we describe a novel genome browser based on the Biodalliance platform developed to provide interactive access to the association results of the project.

Comparative analysis of the transcriptome across distant species.

The transcriptome is the readout of the genome. Identifying common features in it across distant species can reveal fundamental principles. To this end, the ENCODE and modENCODE consortia have generated large amounts of matched RNA-sequencing data for human, worm and fly.

Characterizing genetic variants for clinical action.

Genome-wide association studies, DNA sequencing studies, and other genomic studies are finding an increasing number of genetic variants associated with clinical phenotypes that may be useful in developing diagnostic, preventive, and treatment strategies for individual patients. However, few variants have been integrated into routine clinical practice. The reasons for this are several, but two of the most significant are limited evidence about the clinical implications of the variants and a lack of a comprehensive knowledge base that captures genetic variants, their phenotypic associations, and other pertinent phenotypic information that is openly accessible to clinical groups attempting to interpret sequencing data.

Ensembl 2014.

Ensembl (http://www.ensembl.org) creates tools and data resources to facilitate genomic analysis in chordate species with an emphasis on human, major vertebrate model organisms and farm animals.

Assessment of transcript reconstruction methods for RNA-seq.

We evaluated 25 protocol variants of 14 independent computational methods for exon identification, transcript reconstruction and expression-level quantification from RNA-seq data. Our results show that most algorithms are able to identify discrete transcript components with high success rates but that assembly of complete isoform structures poses a major challenge even when all constituent elements are identified. Expression-level estimates also varied widely across methods, even when based on similar transcript models.

Systematic evaluation of spliced alignment programs for RNA-seq data.

High-throughput RNA sequencing is an increasingly accessible method for studying gene structure and activity on a genome-wide scale. A critical step in RNA-seq data analysis is the alignment of partial transcript reads to a reference genome sequence. To assess the performance of current mapping software, we invited developers of RNA-seq aligners to process four large human and mouse RNA-seq data sets.

Chromatin accessibility data sets show bias due to sequence specificity of the DNase I enzyme.

Background: DNase I is an enzyme which cuts duplex DNA at a rate that depends strongly upon its chromatin environment. In combination with high-throughput sequencing (HTS) technology, it can be used to infer genome-wide landscapes of open chromatin regions. Using this technology, systematic identification of hundreds of thousands of DNase I hypersensitive sites (DHS) per cell type has been possible, and this in turn has helped to precisely delineate genomic regulatory compartments.

The zebrafish reference genome sequence and its relationship to the human genome.

Zebrafish have become a popular organism for the study of vertebrate gene function. The virtually transparent embryos of this species, and the ability to accelerate genetic studies by gene knockdown or overexpression, have led to the widespread use of zebrafish in the detailed investigation of vertebrate gene function and increasingly, the study of human genetic disease. However, for effective modelling of human genetic disease it is important to understand the extent to which zebrafish genes and gene structures are related to orthologous human genes.

Ensembl 2013.

The Ensembl project (http://www.ensembl.org) provides genome information for sequenced chordate genomes with a particular focus on human, mouse, zebrafish and rat.

The GENCODE v7 catalog of human long noncoding RNAs: analysis of their gene structure, evolution, and expression.

The human genome contains many thousands of long noncoding RNAs (lncRNAs). While several studies have demonstrated compelling biological and disease roles for individual examples, analytical and experimental approaches to investigate these genes have been hampered by the lack of comprehensive lncRNA annotation. Here, we present and analyze the most complete human lncRNA annotation to date, produced by the GENCODE consortium within the framework of the ENCODE project and comprising 9277 manually annotated genes producing 14,880 transcripts.

Combining RT-PCR-seq and RNA-seq to catalog all genic elements encoded in the human genome.

Within the ENCODE Consortium, GENCODE aimed to accurately annotate all protein-coding genes, pseudogenes, and noncoding transcribed loci in the human genome through manual curation and computational methods. Annotated transcript structures were assessed, and less well-supported loci were systematically, experimentally validated. Predicted exon-exon junctions were evaluated by RT-PCR amplification followed by highly multiplexed sequencing readout, a method we called RT-PCR-seq.

The GENCODE pseudogene resource.

Background: Pseudogenes have long been considered as nonfunctional genomic sequences. However, recent evidence suggests that many of them might have some form of biological activity, and the possibility of functionality has increased interest in their accurate annotation and integration with functional genomics data.

Results: As part of the GENCODE annotation of the human genome, we present the first genome-wide pseudogene assignment for protein-coding genes, based on both large-scale manual annotation and in silico pipelines.

Ensembl 2012.

The Ensembl project (http://www.ensembl.org) provides genome resources for chordate genomes with a particular focus on human genome data as well as data for key model organisms such as mouse, rat and zebrafish.

Developing and implementing an institute-wide data sharing policy.

The Wellcome Trust Sanger Institute has a strong reputation for prepublication data sharing as a result of its policy of rapid release of genome sequence data and particularly through its contribution to the Human Genome Project. The practicalities of broad data sharing remain largely uncharted, especially to cover the wide range of data types currently produced by genomic studies and to adequately address ethical issues. This paper describes the processes and challenges involved in implementing a data sharing policy on an institute-wide scale.

The GENCODE exome: sequencing the complete human exome.

Sequencing the coding regions, the exome, of the human genome is one of the major current strategies to identify low frequency and rare variants associated with human disease traits. So far, the most widely used commercial exome capture reagents have mainly targeted the consensus coding sequence (CCDS) database. We report the design of an extended set of targets for capturing the complete human exome, based on annotation from the GENCODE consortium.

Dalliance: interactive genome viewing on the web.

Summary: Dalliance is a new genome viewer which offers a high level of interactivity while running within a web browser. All data is fetched using the established distributed annotation system (DAS) protocol, making it easy to customize the browser and add extra data.

Availability And Implementation: Dalliance runs entirely within your web browser, and relies on existing DAS server infrastructure.

Ensembl 2011.

The Ensembl project (http://www.ensembl.org) seeks to enable genomic science by providing high quality, integrated annotation on chordate and selected eukaryotic genomes within a consistent and accessible infrastructure.

Metamotifs--a generative model for building families of nucleotide position weight matrices.

Background: Development of high-throughput methods for measuring DNA interactions of transcription factors together with computational advances in short motif inference algorithms is expanding our understanding of transcription factor binding site motifs. The consequential growth of sequence motif data sets makes it important to systematically group and categorise regulatory motifs. It has been shown that there are familial tendencies in DNA sequence motifs that are predictive of the family of factors that binds them.

International network of cancer genome projects.

The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.

iMotifs: an integrated sequence motif visualization and analysis environment.

Motivation: Short sequence motifs are an important class of models in molecular biology, used most commonly for describing transcription factor binding site specificity patterns. High-throughput methods have been recently developed for detecting regulatory factor binding sites in vivo and in vitro and consequently high-quality binding site motif data are becoming available for increasing number of organisms and regulatory factors. Development of intuitive tools for the study of sequence motifs is therefore important.