POXO: a web-enabled tool series to discover transcription factor binding sites

We present POXO, a comprehensive tool series to discover transcription factor binding sites from co-expressed genes (). POXO manages tasks such as functional evaluation and grouping of genes, sequence retrieval, pattern discovery and pattern verification. It also allows users to tailor analytical pipelines from these tools, with single mouse clicks. One typical pipeline of POXO begins by examining the biological functions that a set of co-expressed genes are involved in. In this examination, the functional coherence of the gene set is evaluated and representative functions are associated with the gene set. This examination can also be used to group genes into functionally similar subsets, if several biological processes are affected in the experiment. The next step in the pipeline is then to discover over-represented nucleotide patterns from the upstream sequences of the selected gene sets. This enables to investigate the possibility that the genes are co-regulated by common cis-elements. If over-represented patterns are found, similar ones can then be clustered together and be verified. The performance of POXO is demonstrated by analysing expression data from pathogen treated Arabidopsis thaliana. In this example, POXO detected activated gene sets and suggested transcription factors responsible for their regulation

Generation of Gene Ontology benchmark datasets with various types of positive signal

Peer reviewe

Biomarkers and long-term labour market outcomes: the case of creatine

Using the Young Finns Study (YFS) combined with the Finnish Linked Employer-Employee Data (FLEED) we show that quantities of creatine measured in 1980 prior to labour market entry affect labour market outcomes over the period 1990-2010. Those with higher levels of creatine (proxied by urine creatinine) prior to labour market entry spend more time in the labour market in the subsequent two decades and earn more. Creatine is not associated with high educational attainment. The associations between creatine and labour market outcomes are robust to controlling for other biomarkers, educational attainment and parental background. Creatine is a naturally occurring nitrogenous organic acid which supplies energy to body cells, including muscles. Our findings are consistent with high energy levels, induced by creatine, leading to productivity-enhancing traits such as a high propensity for effort, perseverance, and high-commitment.</div

Schizophrenia polygenic risk score and long-term success in the labour market : A cohort study

Publisher Copyright: © 2022 The AuthorsEmployment is rare among people with a schizophrenia diagnosis. Meanwhile, a genetic liability for schizophrenia may hinder labour market performance. We studied how the polygenic risk score (PGS) for schizophrenia related to education and labour market outcomes. We found that a higher PGS was linked to lower educational levels and weaker labour market outcomes as well as a higher likelihood of receiving social income transfers, particularly among men. Assuming that the link is causal, our results indicate that individuals with schizophrenia or schizophrenia-related traits have a weakened ability to fully participate in the labour market, potentially reinforcing social exclusion.Peer reviewe

Creatine and entrepreneurship

Creatine is a nitrogenous organic acid which supplies energy to body cells and enhances physical performance. Using the Young Finns Study combined with the Finnish Linked employer-employee data we show that quantities of creatine measured in 1980 prior to labour market entry affect entrepreneurial success as measured by capital income accumulation over the period 1993–2010 (in particular for females). However, we do not find evidence that creatine affects the propensity to become an entrepreneur. Our study contributes to the emerging literature on biomarkers and entrepreneurship

Does higher education protect against obesity? Evidence using Mendelian randomization

Objectives. The aim of this explorative study was to examine the effect of education on obesity using Mendelian randomization. Methods. Participants (N = 2011) were from the on- going nationally representative Young Finns Study (YFS) that began in 1980 when six cohorts (aged 30, 33, 36, 39, 42 and 45 in 2007) were recruited. The average value of BMI (kg/m(2)) measurements in 2007 and 2011 and genetic information were linked to comprehensive register based information on the years of education in 2007. We first used a linear regression (Ordinary Least Squares, OLS) to estimate the relationship between education and BMI. To identify a causal relationship, we exploited Mendelian randomization and used a genetic score as an instrument for education. The genetic score was based on 74 genetic variants that genome- wide association studies (GWASs) have found to be associated with the years of education. Because the genotypes are randomly assigned at conception, the instrument causes exogenous variation in the years of education and thus enables identification of causal effects. Results. The years of education in 2007 were associated with lower BMI in 2007/2011 (regression coefficient (b) = -0.22; 95% Confidence Intervals [CI] = -0.29,-0.14) according to the linear regression results. The results based on Mendelian randomization suggests that there may be a negative causal effect of education on BMI (b = -0.84; 95% CI = -1.77, 0.09). Conclusion. The findings indicate that education could be a protective factor against obesity in advanced countries. (C) 2017 Elsevier Inc. All rights reserved.Peer reviewe

Genome-wide landscape of liver X receptor chromatin binding and gene regulation in human macrophages

<p>Abstract</p> <p>Background</p> <p>The liver X receptors (LXRs) are oxysterol sensing nuclear receptors with multiple effects on metabolism and immune cells. However, the complete genome-wide cistrome of LXR in cells of human origin has not yet been provided.</p> <p>Results</p> <p>We performed ChIP-seq in phorbol myristate acetate-differentiated THP-1 cells (macrophage-type) after stimulation with the potent synthetic LXR ligand T0901317 (T09). Microarray gene expression analysis was performed in the same cellular model. We identified 1357 genome-wide LXR locations (FDR < 1%), of which 526 were observed after T09 treatment. <it>De novo </it>analysis of LXR binding sequences identified a DR4-type element as the major motif. On mRNA level T09 up-regulated 1258 genes and repressed 455 genes. Our results show that LXR actions are focused on 112 genomic regions that contain up to 11 T09 target genes per region under the control of highly stringent LXR binding sites with individual constellations for each region. We could confirm that LXR controls lipid metabolism and transport and observed a strong association with apoptosis-related functions.</p> <p>Conclusions</p> <p>This first report on genome-wide binding of LXR in a human cell line provides new insights into the transcriptional network of LXR and its target genes with their link to physiological processes, such as apoptosis.</p> <p>The gene expression microarray and sequence data have been submitted collectively to the NCBI Gene Expression Omnibus <url>http://www.ncbi.nlm.nih.gov/geo</url> under accession number GSE28319.</p

Birth weight and adult income: An examination of mediation through adult height and body mass

This paper examines the causal links between early human endowments and socioeconomic outcomes in adulthood. We use a genotyped longitudinal survey (Cardiovascular Risk in Young Finns Study) that is linked to the administrative registers of Statistics Finland. We focus on the effect of birth weight on income via two anthropometric mediators: body mass index (BMI) and height in adulthood. We find that (i) the genetic instruments for birth weight, adult height, and adult BMI are statistically powerful; (ii) there is a robust total effect of birth weight on income for men but not for women; (iii) the total effect of birth weight on income for men is partly mediated via height but not via BMI; and (iv) the share of the total effect mediated via height is substantial, of approximately 56%

TAFFEL: Independent Enrichment Analysis of gene sets

<p>Abstract</p> <p>Background</p> <p>A major challenge in genomic research is identifying significant biological processes and generating new hypotheses from large gene sets. Gene sets often consist of multiple separate biological pathways, controlled by distinct regulatory mechanisms. Many of these pathways and the associated regulatory mechanisms might be obscured by a large number of other significant processes and thus not identified as significant by standard gene set enrichment analysis tools.</p> <p>Results</p> <p>We present a novel method called Independent Enrichment Analysis (IEA) and software TAFFEL that eases the task by clustering genes to subgroups using Gene Ontology categories and transcription regulators. IEA indicates transcriptional regulators putatively controlling biological functions in studied condition.</p> <p>Conclusions</p> <p>We demonstrate that the developed method and TAFFEL tool give new insight to the analysis of differentially expressed genes and can generate novel hypotheses. Our comparison to other popular methods showed that the IEA method implemented in TAFFEL can find important biological phenomena, which are not reported by other methods.</p

Mesenchymal cell-derived Wnt1 signaling regulates subchondral bone remodeling but has no effects on the development of growth plate or articular cartilage in mice

Chondrocyte differentiation is a principal progress in endochondral ossification and in the formation of secondary ossification center (SOC) during the long bone development. We have previously reported that targeted deletion of Wnt1 in mesenchymal progenitors (Wnt1Prrx-/-) leads to spontaneous fractures and severe osteopenia in mouse long bones, suggesting that Wnt1 is a key regulator of bone metabolism. However, the effect of Wnt1 on the regulation of cartilage development and chondrocyte differentiation remained unknown. In this study, WNT1 protein expression was observed in lateral superficial cartilage and growth plate pre-hypertrophic chondrocytes in mice. Wnt1 mRNA expression was detected in epiphyseal cartilage from E16.5 to 3 month-old mice. Detailed histological analyses revealed that the average thickness and chondrocyte density of proximal tibial articular cartilage and growth plate were unchanged between Wnt1Prrx-/- and control mice. However, mu CT analysis of tibial epiphyses showed that the subchondral bone mass was reduced in Wnt1Prrx-/- mice compared to control mice, as demonstrated by decreased bone volume, trabecular number, trabecular thickness, and increased trabecular separation in Wnt1Prrx-/- mice. Mechanistically, histomorphometric analyses showed that the reduced subchondral bone mass in Wnt1Prrx-/- mice was due to impaired bone formation and enhanced bone resorption. In vitro, exogenous Wntl inhibited chondrogenesis and chondrocyte hypertrophy in both cell autonomous and juxtacrine manners, while matrix mineralization and the expression of Mmp13, Mmp9 and Opn were induced in a juxtacrine manner. Taken together, mesenchymal cell-derived Wntl is an important regulator of subchondral bone remodeling, although it has no effect on the regulation of growth plate or articular cartilage.</p