Natural genetic variation impacts expression levels of coding, non-coding, and antisense transcripts in fission yeast.

Our current understanding of how natural genetic variation affects gene expression beyond well-annotated coding genes is still limited. The use of deep sequencing technologies for the study of expression quantitative trait loci (eQTLs) has the potential to close this gap. Here, we generated the first recombinant strain library for fission yeast and conducted an RNA-seq-based QTL study of the coding, non-coding, and antisense transcriptomes.

The transcriptome of corona radiata cells from individual MІІ oocytes that after ICSI developed to embryos selected for transfer: PCOS women compared to healthy women.

Background: Corona radiata cells (CRCs) refer to the fraction of cumulus cells just adjacent to the oocyte. The CRCs are closely connected to the oocyte throughout maturation and their gene expression profiles might reflect oocyte quality. Polycystic ovary syndrome (PCOS) is a common cause of infertility.

The microbiome of New World vultures.

Vultures are scavengers that fill a key ecosystem niche, in which they have evolved a remarkable tolerance to bacterial toxins in decaying meat. Here we report the first deep metagenomic analysis of the vulture microbiome. Through face and gut comparisons of 50 vultures representing two species, we demonstrate a remarkably conserved low diversity of gut microbial flora.

Cyclebase 3.0: a multi-organism database on cell-cycle regulation and phenotypes.

The eukaryotic cell division cycle is a highly regulated process that consists of a complex series of events and involves thousands of proteins. Researchers have studied the regulation of the cell cycle in several organisms, employing a wide range of high-throughput technologies, such as microarray-based mRNA expression profiling and quantitative proteomics. Due to its complexity, the cell cycle can also fail or otherwise change in many different ways if important genes are knocked out, which has been studied in several microscopy-based knockdown screens.

Renal impairment and late toxicity in germ-cell cancer survivors.

Background: Treatment with bleomycin-etoposide-cisplatin (BEP) impairs renal function and increases the risk of late cardiovascular disease (CVD) and death. We investigated the influence of BEP on glomerular filtration rate (GFR) and assessed the importance of GFR changes on CVD and death in a large cohort of germ-cell cancer survivors.

Patients And Methods: BEP-treated patients (N = 1206) were identified in the Danish DaTeCa database, and merged with national registers to identify late toxicity.

Sequenza: allele-specific copy number and mutation profiles from tumor sequencing data.

Background: Exome or whole-genome deep sequencing of tumor DNA along with paired normal DNA can potentially provide a detailed picture of the somatic mutations that characterize the tumor. However, analysis of such sequence data can be complicated by the presence of normal cells in the tumor specimen, by intratumor heterogeneity, and by the sheer size of the raw data. In particular, determination of copy number variations from exome sequencing data alone has proven difficult; thus, single nucleotide polymorphism (SNP) arrays have often been used for this task.

SNPsnap: a Web-based tool for identification and annotation of matched SNPs.

Summary: An important computational step following genome-wide association studies (GWAS) is to assess whether disease or trait-associated single-nucleotide polymorphisms (SNPs) enrich for particular biological annotations. SNP-based enrichment analysis needs to account for biases such as co-localization of GWAS signals to gene-dense and high linkage disequilibrium (LD) regions, and correlations of gene size, location and function. The SNPsnap Web server enables SNP-based enrichment analysis by providing matched sets of SNPs that can be used to calibrate background expectations.

Whey-reduced weight gain is associated with a temporary growth reduction in young mice fed a high-fat diet.

Whey protein consumption reportedly alleviates parameters of the metabolic syndrome. Here, we investigated the effects of whey protein isolate (whey) in young mice fed a high-fat diet. We hypothesized that whey as the sole protein source reduced early weight gain associated with retarded growth and decreased concentration of insulin-like growth factor-1.

Uncovering the peptide-binding specificities of HLA-C: a general strategy to determine the specificity of any MHC class I molecule.

MHC class I molecules (HLA-I in humans) present peptides derived from endogenous proteins to CTLs. Whereas the peptide-binding specificities of HLA-A and -B molecules have been studied extensively, little is known about HLA-C specificities. Combining a positional scanning combinatorial peptide library approach with a peptide-HLA-I dissociation assay, in this study we present a general strategy to determine the peptide-binding specificity of any MHC class I molecule.

Characterizing the human hematopoietic CDome.

In this study, we performed extensive semi-automated data collection from the primary and secondary literature in an effort to characterize the expression of all membrane proteins within the CD scheme on hematopoietic cells. Utilizing over 6000 data points across 305 CD molecules on 206 cell types, we seek to give a preliminary characterization of the "human hematopoietic CDome." We encountered severe gaps in the knowledge of CD protein expression, mostly resulting from incomplete and unstructured data generation, which we argue inhibit both basic research as well as therapies seeking to target membrane proteins.

Tabhu: tools for antibody humanization.

Summary: Antibodies are rapidly becoming essential tools in the clinical practice, given their ability to recognize their cognate antigens with high specificity and affinity, and a high yield at reasonable costs in model animals. Unfortunately, when administered to human patients, xenogeneic antibodies can elicit unwanted and dangerous immunogenic responses. Antibody humanization methods are designed to produce molecules with a better safety profile still maintaining their ability to bind the antigen.

Defining the role of common variation in the genomic and biological architecture of adult human height.

Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated ∼2,000, ∼3,700 and ∼9,500 SNPs explained ∼21%, ∼24% and ∼29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability.

A novel common variant in DCST2 is associated with length in early life and height in adulthood.

Common genetic variants have been identified for adult height, but not much is known about the genetics of skeletal growth in early life. To identify common genetic variants that influence fetal skeletal growth, we meta-analyzed 22 genome-wide association studies (Stage 1; N = 28 459). We identified seven independent top single nucleotide polymorphisms (SNPs) (P < 1 × 10(-6)) for birth length, of which three were novel and four were in or near loci known to be associated with adult height (LCORL, PTCH1, GPR126 and HMGA2).

Hybridization capture using short PCR products enriches small genomes by capturing flanking sequences (CapFlank).

Solution hybridization capture methods utilize biotinylated oligonucleotides as baits to enrich homologous sequences from next generation sequencing (NGS) libraries. Coupled with NGS, the method generates kilo to gigabases of high confidence consensus targeted sequence. However, in many experiments, a non-negligible fraction of the resulting sequence reads are not homologous to the bait.

Patient stratification and identification of adverse event correlations in the space of 1190 drug related adverse events.

Purpose: New pharmacovigilance methods are needed as a consequence of the morbidity caused by drugs. We exploit fine-grained drug related adverse event information extracted by text mining from electronic medical records (EMRs) to stratify patients based on their adverse events and to determine adverse event co-occurrences.

Methods: We analyzed the similarity of adverse event profiles of 2347 patients extracted from EMRs from a mental health center in Denmark.

Rescue of the highly virulent classical swine fever virus strain "Koslov" from cloned cDNA and first insights into genome variations relevant for virulence.

Classical swine fever virus (CSFV) strain "Koslov" is highly virulent with a mortality rate of up to 100% in pigs. In this study, we modified non-functional cDNAs generated from the blood of Koslov virus infected pigs by site-directed mutagenesis, removing non-synonymous mutations step-by-step, thereby producing genomes encoding the consensus amino acid sequence. Viruses rescued from the construct corresponding to the inferred parental form were highly virulent, when tested in pigs, with infected animals displaying pronounced clinical symptoms leading to high mortality.

Interpretation of appearance: the effect of facial features on first impressions and personality.

Appearance is known to influence social interactions, which in turn could potentially influence personality development. In this study we focus on discovering the relationship between self-reported personality traits, first impressions and facial characteristics. The results reveal that several personality traits can be read above chance from a face, and that facial features influence first impressions.

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear.

Airway mucosal immune-suppression in neonates of mothers receiving A(H1N1)pnd09 vaccination during pregnancy.

Background: It is recommended to vaccinate pregnant women against influenza. A possible impact on the immune expression of the fetus has never been studied. We aim to study the immune signature in the upper airways and the incidence of infections in neonates born to mothers receiving Influenza A(H1N1)pnd09 vaccination during pregnancy.

Mycobacterium tuberculosis promotes Th17 expansion via regulation of human dendritic cells toward a high CD14 and low IL-12p70 phenotype that reprograms upon exogenous IFN-γ.

The capacity to develop protective immunity against mycobacteria is heterogeneously distributed among human beings, and it is currently unknown why the initial immune response induced against Mycobacterium tuberculosis (Mtb) does not provide proper clearance of this pathogen. Dendritic cells (DCs) are some of the first cells to interact with Mtb and they play an essential role in development of protective immunity against Mtb. Given that Mtb-infected macrophages have difficulties in degrading Mtb, they need help from IFN-γ-producing CD4+ T cells propagated via IL-12p70-producing DCs.

In silico prediction of Gallibacterium anatis pan-immunogens.

The Gram-negative bacterium Gallibacterium anatis is a major cause of salpingitis and peritonitis in commercial egg-layers, leading to reduced egg production and increased mortality. Unfortunately, widespread multidrug resistance and antigenic diversity makes it difficult to control infections and novel prevention strategies are urgently needed. In this study, a pan-genomic reverse vaccinology (RV) approach was used to identify potential vaccine candidates.

Chronic obstructive pulmonary disease and asthma-associated Proteobacteria, but not commensal Prevotella spp., promote Toll-like receptor 2-independent lung inflammation and pathology.

Recent studies of healthy human airways have revealed colonization by a distinct commensal bacterial microbiota containing Gram-negative Prevotella spp. However, the immunological properties of these bacteria in the respiratory system remain unknown. Here we compare the innate respiratory immune response to three Gram-negative commensal Prevotella strains (Prevotella melaninogenica, Prevotella nanceiensis and Prevotella salivae) and three Gram-negative pathogenic Proteobacteria known to colonize lungs of patients with chronic obstructive pulmonary disease (COPD) and asthma (Haemophilus influenzae B, non-typeable Haemophilus influenzae and Moraxella catarrhalis).

Lineage-specific interface proteins match up the cell cycle and differentiation in embryo stem cells.

The shortage of molecular information on cell cycle changes along embryonic stem cell (ESC) differentiation prompts an in silico approach, which may provide a novel way to identify candidate genes or mechanisms acting in coordinating the two programs. We analyzed germ layer specific gene expression changes during the cell cycle and ESC differentiation by combining four human cell cycle transcriptome profiles with thirteen in vitro human ESC differentiation studies. To detect cross-talk mechanisms we then integrated the transcriptome data that displayed differential regulation with protein interaction data.

The genetic prehistory of the New World Arctic.

The New World Arctic, the last region of the Americas to be populated by humans, has a relatively well-researched archaeology, but an understanding of its genetic history is lacking. We present genome-wide sequence data from ancient and present-day humans from Greenland, Arctic Canada, Alaska, Aleutian Islands, and Siberia. We show that Paleo-Eskimos (~3000 BCE to 1300 CE) represent a migration pulse into the Americas independent of both Native American and Inuit expansions.