Genome-wide search for exonic variants affecting translational efficiency
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE46195 | GEO | 2013/04/18
SECONDARY ACCESSION(S): PRJNA198016
REPOSITORIES: GEO
Similar Datasets
Project description:The search for expression quantitative trait loci has traditionally centred entirely on the process of transcription, whereas variants with effects on messenger RNA translation have not been systematically studied. Here we present a high-throughput approach for measuring translational cis-regulation in the human genome. Using ribosomal association as proxy for translational efficiency of polymorphic messenger RNAs, we test the ratio of polysomal/non-polysomal messenger RNA level as a quantitative trait for association with single nucleotide polymorphisms on the same messenger RNA transcript. We identify one important ribosomal distribution effect, from rs1131017 in the 5'-untranslated region of RPS26, that is in high linkage disequilibrium with the 12q13 locus for susceptibility to type 1 diabetes. The effect on translation is confirmed at the protein level by quantitative western blots, both ex vivo and after in vitro translation. Our results are a proof-of-principle that allelic effects on translation can be detected at a transcriptome-wide scale.
| S-EPMC3749366 | biostudies-literature
Project description:Background: Cases where genotype-phenotype relationships depend on environmental factors have been quantified for many complex diseases. Such genotype-environment interactions (GEI or GxE) may also affect expression Quantitative Trait Loci (eQTL) present in tissues critical for the manifestation of disease. To assess this hypothesis, we performed an analysis of eQTL-GEI resulting from an individual's smoking environment in the lung small airway epithelium (SAE). While the SAE is challenging to sample, this is the cell population that shows the first signs of smoking related stress and gene expression in the SAE appears to play a role in mediating smoking effects on lung disease. Results: We used expression microarrays to assay the SAE transcriptome for a small sample of African-American individuals and we analyzed SNPs genotyped genome-wide to identify GEI affecting eQTL. While a genome-wide trans- analysis identified few instances of GEI after a multiple test correction, an analysis of cis-genotypes identified a small but significant number of GEI affecting lung SAE gene expression. We determined that significant cases of eQTL-GEI were not driven by outliers and we were also able to find corroborative evidence for a few of these eQTL-GEI in a small, independent sample of individuals of European ancestry. Conclusion: Given that the power of GEI tests is low compared to tests of genotype association and that the total sample size of our study was small, including only 61 African American individuals in our focal population, the identification of significant GEI in our study implies that there may be considerable genotype-specific effects on eQTL due to smoking environment. We discuss individual cases of GEI of interest for lung disease, such as SDC1 and ZAK, as well as the broader implications of our results for the analysis of eQTL and for genome-wide association analysis of complex diseases.
2024-06-05 | GSE23087 | GEO
Project description: Not available
| S-EPMC6137559 | biostudies-literature
Project description:eQTL analysis of 5 DAP Zea mays (maize) kernels
2020-04-16 | E-GEOD-110315 | ExpressionAtlas
Project description:The enormous size of mammalian genomes means that for a DNA-binding protein the number of nonspecific, off-target sites vastly exceeds the number of specific, cognate sites. How mammalian DNA-binding proteins overcome this challenge to efficiently locate their target sites is not known. Here, through live-cell single-molecule tracking, we show that CCCTC-binding factor, CTCF, is repeatedly trapped in small zones that likely correspond to CTCF clusters, in a manner that is largely dependent on an internal RNA-binding region (RBRi). We develop a new theoretical model called anisotropic diffusion through transient trapping in zones to explain CTCF dynamics. Functionally, transient RBRi-mediated trapping increases the efficiency of CTCF target search by ~2.5-fold. Overall, our results suggest a 'guided' mechanism where CTCF clusters concentrate diffusing CTCF proteins near cognate binding sites, thus increasing the local ON-rate. We suggest that local guiding may allow DNA-binding proteins to more efficiently locate their target sites.
| S-EPMC7036004 | biostudies-literature
Project description:BackgroundMeasuring hospital efficiency is a systematic process to optimizing performance and resource allocation. The current review study has investigated the key input, process, and output indicators that are commonly used in measuring the technical efficiency of the hospital to promote the accuracy of the results.MethodsTo conduct this systematic review, the electronic resources and databases MEDLINE (via PubMed), Scopus, Ovid, Proquest, Google Scholar, and reference lists of the selected articles were used for searching articles between 2010 and 2019. After in-depth reviews based on the inclusion and exclusion criteria, among 1,537 studies, 144 articles were selected for the final assessment. Critical Appraisal Skills Programme (CASP) Checklist was used for evaluating the quality of the articles. The main findings of studies have been extracted using content analysis.ResultsAfter the final analysis, the Context/Input indicators that were commonly considered by studies in analyzing hospital technical efficiency include different variables related to Hospital Capacity, Structure, Characteristics, Market concentration, and Costs. The Process/Throughput indicators include different variables related to Hospital Activity or services-oriented process Indicators, Hospital Quality-oriented process indicators, and Hospital Educational processes. Finally, the Output/Outcome indicators include different variables related to Hospital Activity-related output variables and Quality-related output/outcomes variables.ConclusionThis study has identified that it is necessary to mix and assess a set of input, process, and output indicators of the hospital with both quantitative and qualitative indicators for measuring the technical efficiency of hospitals comprehensively.
| S-EPMC8964142 | biostudies-literature
Project description:BackgroundSystematic reviews are comprehensive, robust, inclusive, transparent, and reproducible when bringing together the evidence to answer a research question. Various guidelines provide recommendations on the expertise required to conduct a systematic review, where and how to search for literature, and what should be reported in the published review. However, the finer details of the search results are not typically reported to allow the search methods or search efficiency to be evaluated.Case presentationThis case study presents a search summary table, containing the details of which databases were searched, which supplementary search methods were used, and where the included articles were found. It was developed and published alongside a recent systematic review. This simple format can be used in future systematic reviews to improve search results reporting.ConclusionsPublishing a search summary table in all systematic reviews would add to the growing evidence base about information retrieval, which would help in determining which databases to search for which type of review (in terms of either topic or scope), what supplementary search methods are most effective, what type of literature is being included, and where it is found. It would also provide evidence for future searching and search methods research.
| S-EPMC7772975 | biostudies-literature
Project description:Nearly all motile organisms must search for food, often requiring multiple phases of exploration across heterogeneous environments. The fruit fly, Drosophila, has emerged as an effective model system for studying this behavior; however, little is known about the extent to which experiences at one point in their search might influence decisions in another. To investigate whether prior experiences impact flies' search behavior after landing, I tracked individually labelled fruit flies as they explored three odor-emitting but food-barren objects. I found two features of their behavior that are correlated with the distance they travel on foot. First, flies walked larger distances when they approached the odor source, which they were almost twice as likely to do when landing on the patch farthest downwind. Computational fluid dynamics simulations suggest this patch may have had a stronger baseline odor, but only ∼15% higher than the other two patches. This small increase, together with flies' high olfactory sensitivity, suggests that their flight trajectory used to approach the patches plays a role. Second, flies also walked larger distances when the time elapsed since their last visit was longer. However, the correlation is subtle and subject to a large degree of variability. Using agent-based models, I show that this small correlation can increase search efficiency by 25-50% across many scenarios. Furthermore, my models provide mechanistic hypotheses explaining the variability through either a noisy or stochastic decision-making process. Surprisingly, these stochastic decision-making algorithms enhance search efficiency in challenging but realistic search scenarios compared with deterministic strategies.
| S-EPMC8407661 | biostudies-literature
Project description:RNA-seq of human islet pancreatic cells to identify eQTL loci
2020-04-24 | E-ENAD-42 | ExpressionAtlas
Project description:Intra-uterine growth restriction (IUGR) and fetal overgrowth increase the risk of postnatal health. Maternal nutrition is the major intrauterine environmental factor that alters fetal weight. However, the mechanisms underlying maternal nutrition affect fetal development is not entirely clear. We developed a pig model and used isobaric tags for relative and absolute quantification (iTRAQ) to investigate alterations in the placental proteome were obtained from gilts in normal-energy-intake (Con) and high-energy-intake (HE) group, respectively.At 90 d of gestation, the heavy fetuses were found at the tubal ends and light fetuses at the cervical ends of the uterus in Con group and the heavy fetuses had higher glucose concentration than the light fetuses. However, a higher uniformity was noted in HE group. Placental promote between these two positions indicated that a total of 78 and 50 differentially expressed proteins were detected in Con and HE group, respectively. In Con group, these proteins related to lipid metabolism (HADHA, AACS, CAD), nutrient transport (GLUT, SLC27A1) and energy metabolism (NDUFV1, NDUFV2, ATP5C1). However, the differentially expressed proteins in HE group were mainly participation in transcriptional and translational regulation and intracellular vesicular transport.
2018-10-26 | PXD004951 | Pride