Multi-omic biomarker panel in pancreatic cyst fluid and serum predicts patients at a high risk of pancreatic cancer development.

Integration of multi-omic data for the purposes of biomarker discovery can provide novel and robust panels across multiple biological compartments. Appropriate analytical methods are key to ensuring accurate and meaningful outputs in the multi-omic setting. Here, we extensively profile the proteome and transcriptome of patient pancreatic cyst fluid (PCF) (n = 32) and serum (n = 68), before integrating matched omic and biofluid data, to identify biomarkers of pancreatic cancer risk.

The origins of the Guinness stout yeast.

Beer is made via the fermentation of an aqueous extract predominantly composed of malted barley flavoured with hops. The transforming microorganism is typically a single strain of Saccharomyces cerevisiae, and for the majority of major beer brands the yeast strain is a unique component. The present yeast used to make Guinness stout brewed in Dublin, Ireland, can be traced back to 1903, but its origins are unknown.

Transcriptome analysis of the mouse E14.5 (TS23) developing humerus and differential expression in muscle-less mutant embryos lacking mechanical stimulation.

Mechanical stimulation is important for the correct formation of the skeleton. Splotch-delayed mutant embryos (Pax3 (Spd/Spd) ) that develop with no limb muscle and therefore no limb movement experience an altered mechanical environment resulting in specific defects in ossification and joint formation, particularly in the forelimb. To test the hypothesis that mechanical stimuli influence the regulation of genes important in skeletal development we generated a transcriptome profile of the developing humerus at Theiler stage 23 (TS23), and then identified differentially expressed genes in muscle-less mutant embryos compared to control littermates.

Translation of 5' leaders is pervasive in genes resistant to eIF2 repression.

Eukaryotic cells rapidly reduce protein synthesis in response to various stress conditions. This can be achieved by the phosphorylation-mediated inactivation of a key translation initiation factor, eukaryotic initiation factor 2 (eIF2). However, the persistent translation of certain mRNAs is required for deployment of an adequate stress response.

Next-generation sequencing of the mitochondrial genome and association with IgA nephropathy in a renal transplant population.

Kidneys are highly aerobic organs that are critically dependent on the normal functioning of mitochondria. Genetic variations disrupting mitochondrial function are associated with multifactorial disorders including kidney disease. This study sequenced the entire mitochondrial genome in a renal transplant cohort of 64 individuals, using next-generation sequencing, to evaluate the association of genetic variants with IgA nephropathy and end-stage renal disease (ESRD, n = 100).

An inherited duplication at the gene p21 Protein-Activated Kinase 7 (PAK7) is a risk factor for psychosis.

Identifying rare, highly penetrant risk mutations may be an important step in dissecting the molecular etiology of schizophrenia. We conducted a gene-based analysis of large (>100 kb), rare copy-number variants (CNVs) in the Wellcome Trust Case Control Consortium 2 (WTCCC2) schizophrenia sample of 1564 cases and 1748 controls all from Ireland, and further extended the analysis to include an additional 5196 UK controls. We found association with duplications at chr20p12.

Identification of mechanosensitive genes during skeletal development: alteration of genes associated with cytoskeletal rearrangement and cell signalling pathways.

Background: Mechanical stimulation is necessary for regulating correct formation of the skeleton. Here we test the hypothesis that mechanical stimulation of the embryonic skeletal system impacts expression levels of genes implicated in developmentally important signalling pathways in a genome wide approach. We use a mutant mouse model with altered mechanical stimulation due to the absence of limb skeletal muscle (Splotch-delayed) where muscle-less embryos show specific defects in skeletal elements including delayed ossification, changes in the size and shape of cartilage rudiments and joint fusion.

Delineating the genetic heterogeneity of ALS using targeted high-throughput sequencing.

Background: Over 100 genes have been implicated in the aetiology of amyotrophic lateral sclerosis (ALS). A detailed understanding of their independent and cumulative contributions to disease burden may help guide various clinical and research efforts.

Methods: Using targeted high-throughput sequencing, we characterised the variation of 10 Mendelian and 23 low penetrance/tentative ALS genes within a population-based cohort of 444 Irish ALS cases (50 fALS, 394 sALS) and 311 age-matched and geographically matched controls.

Development of strategies for SNP detection in RNA-seq data: application to lymphoblastoid cell lines and evaluation using 1000 Genomes data.

Next-generation RNA sequencing (RNA-seq) maps and analyzes transcriptomes and generates data on sequence variation in expressed genes. There are few reported studies on analysis strategies to maximize the yield of quality RNA-seq SNP data. We evaluated the performance of different SNP-calling methods following alignment to both genome and transcriptome by applying them to RNA-seq data from a HapMap lymphoblastoid cell line sample and comparing results with sequence variation data from 1000 Genomes.

Global endometrial transcriptomic profiling: transient immune activation precedes tissue proliferation and repair in healthy beef cows.

Background: All cows experience bacterial contamination and tissue injury in the uterus postpartum, instigating a local inflammatory immune response. However mechanisms that control inflammation and achieve a physiologically functioning endometrium, while avoiding disease in the postpartum cow are not succinctly defined. This study aimed to identify novel candidate genes indicative of inflammation resolution during involution in healthy beef cows.

Gene-ontology enrichment analysis in two independent family-based samples highlights biologically plausible processes for autism spectrum disorders.

Recent genome-wide association studies (GWAS) have implicated a range of genes from discrete biological pathways in the aetiology of autism. However, despite the strong influence of genetic factors, association studies have yet to identify statistically robust, replicated major effect genes or SNPs. We apply the principle of the SNP ratio test methodology described by O'Dushlaine et al to over 2100 families from the Autism Genome Project (AGP).

Multiplex target enrichment using DNA indexing for ultra-high throughput SNP detection.

Screening large numbers of target regions in multiple DNA samples for sequence variation is an important application of next-generation sequencing but an efficient method to enrich the samples in parallel has yet to be reported. We describe an advanced method that combines DNA samples using indexes or barcodes prior to target enrichment to facilitate this type of experiment. Sequencing libraries for multiple individual DNA samples, each incorporating a unique 6-bp index, are combined in equal quantities, enriched using a single in-solution target enrichment assay and sequenced in a single reaction.