Genome Biology

http://genomebiology.com/

List of Papers (Total 5,727)

Chrom3D: three-dimensional genome modeling from Hi-C and nuclear lamin-genome contacts

Current three-dimensional (3D) genome modeling platforms are limited by their inability to account for radial placement of loci in the nucleus. We present Chrom3D, a user-friendly whole-genome 3D computational modeling framework that simulates positions of topologically-associated domains (TADs) relative to each other and to the nuclear periphery. Chrom3D integrates chromosome ...

Human disease genomics: from variants to biology

We summarize the remarkable progress that has been made in the identification and functional characterization of DNA sequence variants associated with disease.

Discovery and functional prioritization of Parkinson’s disease candidate genes from large-scale whole exome sequencing

Background Whole-exome sequencing (WES) has been successful in identifying genes that cause familial Parkinson’s disease (PD). However, until now this approach has not been deployed to study large cohorts of unrelated participants. To discover rare PD susceptibility variants, we performed WES in 1148 unrelated cases and 503 control participants. Candidate genes were subsequently ...

Correcting for cell-type effects in DNA methylation studies: reference-based method outperforms latent variable approaches in empirical studies

Based on an extensive simulation study, McGregor and colleagues recently recommended the use of surrogate variable analysis (SVA) to control for the confounding effects of cell-type heterogeneity in DNA methylation association studies in scenarios where no cell-type proportions are available. As their recommendation was mainly based on simulated data, we sought to replicate ...

Genome-wide mapping of 5-hydroxymethyluracil in the eukaryote parasite Leishmania

Background 5-Hydroxymethyluracil (5hmU) is a thymine base modification found in the genomes of a diverse range of organisms. To explore the functional importance of 5hmU, we develop a method for the genome-wide mapping of 5hmU-modified loci based on a chemical tagging strategy for the hydroxymethyl group. Results We apply the method to generate genome-wide maps of 5hmU in the ...

Response to: Correcting for cell-type effects in DNA methylation studies: reference-based method outperforms latent variable approaches in empirical studies

We thank Hattab and colleagues for their correspondence and their investigation of cell-type mixture correction methods in methyl-CG binding domain sequencing. Here, we speculate on why surrogate variable analysis (SVA) performed differently between their two data sets, and poorly in one of them. Please see related Correspondence article: ...

Controlling bias and inflation in epigenome- and transcriptome-wide association studies using the empirical null distribution

We show that epigenome- and transcriptome-wide association studies (EWAS and TWAS) are prone to significant inflation and bias of test statistics, an unrecognized phenomenon introducing spurious findings if left unaddressed. Neither GWAS-based methodology nor state-of-the-art confounder adjustment methods completely remove bias and inflation. We propose a Bayesian method to control ...

Genome-wide analysis of differential transcriptional and epigenetic variability across human immune cell types

Background A healthy immune system requires immune cells that adapt rapidly to environmental challenges. This phenotypic plasticity can be mediated by transcriptional and epigenetic variability. Results We apply a novel analytical approach to measure and compare transcriptional and epigenetic variability genome-wide across CD14 + CD16 − monocytes, CD66b + CD16 + neutrophils, and ...

Allele-specific analysis of cell fusion-mediated pluripotent reprograming reveals distinct and predictive susceptibilities of human X-linked genes to reactivation

Background Inactivation of one X chromosome is established early in female mammalian development and can be reversed in vivo and in vitro when pluripotency factors are re-expressed. The extent of reactivation along the inactive X chromosome (Xi) and the determinants of locus susceptibility are, however, poorly understood. Here we use cell fusion-mediated pluripotent reprograming to ...

Estimating and accounting for tumor purity in the analysis of DNA methylation data from cancer studies

We present a set of statistical methods for the analysis of DNA methylation microarray data, which account for tumor purity. These methods are an extension of our previously developed method for purity estimation; our updated method is flexible, efficient, and does not require data from reference samples or matched normal controls. We also present a method for incorporating purity ...

Integrated genome-wide analysis of expression quantitative trait loci aids interpretation of genomic association studies

Background Identification of single nucleotide polymorphisms (SNPs) associated with gene expression levels, known as expression quantitative trait loci (eQTLs), may improve understanding of the functional role of phenotype-associated SNPs in genome-wide association studies (GWAS). The small sample sizes of some previous eQTL studies have limited their statistical power. We ...

Single-cell epigenomic variability reveals functional cancer heterogeneity

Background Cell-to-cell heterogeneity is a major driver of cancer evolution, progression, and emergence of drug resistance. Epigenomic variation at the single-cell level can rapidly create cancer heterogeneity but is difficult to detect and assess functionally. Results We develop a strategy to bridge the gap between measurement and function in single-cell epigenomics. Using ...

Gut microbial degradation of organophosphate insecticides-induces glucose intolerance via gluconeogenesis

Background Organophosphates are the most frequently and largely applied insecticide in the world due to their biodegradable nature. Gut microbes were shown to degrade organophosphates and cause intestinal dysfunction. The diabetogenic nature of organophosphates was recently reported but the underlying molecular mechanism is unclear. We aimed to understand the role of gut microbiota ...

Dual RNA-seq reveals viral infections in asthmatic children without respiratory illness which are associated with changes in the airway transcriptome

Background Respiratory illness caused by viral infection is associated with the development and exacerbation of childhood asthma. Little is known about the effects of respiratory viral infections in the absence of illness. Using quantitative PCR (qPCR) for common respiratory viruses and for two genes known to be highly upregulated in viral infections (CCL8/CXCL11), we screened 92 ...

Transcriptomic signatures differentiate survival from fatal outcomes in humans infected with Ebola virus

Background In 2014, Western Africa experienced an unanticipated explosion of Ebola virus infections. What distinguishes fatal from non-fatal outcomes remains largely unknown, yet is key to optimising personalised treatment strategies. We used transcriptome data for peripheral blood taken from infected and convalescent recovering patients to identify early stage host factors that ...

iRegNet3D: three-dimensional integrated regulatory network for the genomic analysis of coding and non-coding disease mutations

The mechanistic details of most disease-causing mutations remain poorly explored within the context of regulatory networks. We present a high-resolution three-dimensional integrated regulatory network (iRegNet3D) in the form of a web tool, where we resolve the interfaces of all known transcription factor (TF)-TF, TF-DNA and chromatin-chromatin interactions for the analysis of both ...

Genome Informatics 2016

A report on the Genome Informatics conference, held at the Wellcome Genome Campus Conference Centre, Hinxton, United Kingdom, 19–22 September 2016.

GAVIN: Gene-Aware Variant INterpretation for medical sequencing

We present Gene-Aware Variant INterpretation (GAVIN), a new method that accurately classifies variants for clinical diagnostic purposes. Classifications are based on gene-specific calibrations of allele frequencies from the ExAC database, likely variant impact using SnpEff, and estimated deleteriousness based on CADD scores for >3000 genes. In a benchmark on 18 clinical gene sets, ...

Insights into the design and interpretation of iCLIP experiments

Background Ultraviolet (UV) crosslinking and immunoprecipitation (CLIP) identifies the sites on RNAs that are in direct contact with RNA-binding proteins (RBPs). Several variants of CLIP exist, which require different computational approaches for analysis. This variety of approaches can create challenges for a novice user and can hamper insights from multi-study comparisons. Here, ...

Identifying aggressive prostate cancer foci using a DNA methylation classifier

Background Slow-growing prostate cancer (PC) can be aggressive in a subset of cases. Therefore, prognostic tools to guide clinical decision-making and avoid overtreatment of indolent PC and undertreatment of aggressive disease are urgently needed. PC has a propensity to be multifocal with several different cancerous foci per gland. Results Here, we have taken advantage of the ...

Distinct 5-methylcytosine profiles in poly(A) RNA from mouse embryonic stem cells and brain

Background Recent work has identified and mapped a range of posttranscriptional modifications in mRNA, including methylation of the N6 and N1 positions in adenine, pseudouridylation, and methylation of carbon 5 in cytosine (m5C). However, knowledge about the prevalence and transcriptome-wide distribution of m5C is still extremely limited; thus, studies in different cell types, ...

Human splicing diversity and the extent of unannotated splice junctions across human RNA-seq samples on the Sequence Read Archive

Background Gene annotations, such as those in GENCODE, are derived primarily from alignments of spliced cDNA sequences and protein sequences. The impact of RNA-seq data on annotation has been confined to major projects like ENCODE and Illumina Body Map 2.0. Results We aligned 21,504 Illumina-sequenced human RNA-seq samples from the Sequence Read Archive (SRA) to the human genome ...

The incredible complexity of RNA splicing

Alternative splice isoforms are common and important and have been shown to impact many human diseases. A new study by Nellore et al. offers a comprehensive study of splice junctions in humans by re-analyzing over 21,500 public human RNA sequencing datasets.

The genome of the Gulf pipefish enables understanding of evolutionary innovations

Background Evolutionary origins of derived morphologies ultimately stem from changes in protein structure, gene regulation, and gene content. A well-assembled, annotated reference genome is a central resource for pursuing these molecular phenomena underlying phenotypic evolution. We explored the genome of the Gulf pipefish (Syngnathus scovelli), which belongs to family Syngnathidae ...

TET enzymes: double agents in the transposable element–host genome conflict

The mouse genome is replete with retrotransposon sequences, from evolutionarily young elements with mutagenic potential that must be controlled, to inactive molecular fossils whose sequences can be domesticated over evolutionary time to benefit the host genome. In an exciting new study, de la Rica and colleagues have uncovered a complex relationship between ten-eleven translocation ...