Adipose Tissue Gene Expression Associations Reveal Hundreds of Candidate Genes for Cardiometabolic Traits

Genome-wide association studies (GWASs) have identified thousands of genetic loci associated with cardiometabolic traits including type 2 diabetes (T2D), lipid levels, body fat distribution, and adiposity, although most causal genes remain unknown. We used subcutaneous adipose tissue RNA-seq data from 434 Finnish men from the METSIM study to identify 9,687 primary and 2,785 secondary cis-expression quantitative trait loci (eQTL; <1 Mb from TSS, FDR < 1%). Compared to primary eQTL signals, secondary eQTL signals were located further from transcription start sites, had smaller effect sizes, and were less enriched in adipose tissue regulatory elements compared to primary signals. Among 2,843 cardiometabolic GWAS signals, 262 colocalized by LD and conditional analysis with 318 transcripts as primary and conditionally distinct secondary cis-eQTLs, including some across ancestries. Of cardiometabolic traits examined for adipose tissue eQTL colocalizations, waist-hip ratio (WHR) and circulating lipid traits had the highest percentage of colocalized eQTLs (15% and 14%, respectively). Among alleles associated with increased cardiometabolic GWAS risk, approximately half (53%) were associated with decreased gene expression level. Mediation analyses of colocalized genes and cardiometabolic traits within the 434 individuals provided further evidence that gene expression influences variant-trait associations. These results identify hundreds of candidate genes that may act in adipose tissue to influence cardiometabolic traits. © 2019 American Society of Human Genetic

Impaired lung function and Health Status in Adult Survivors of Bronchopulmonary Dysplasia

[Abstract]: In recent years, the rapid development of DNA Microarray technology has made it possible for scientists to monitor the expression level of thousands of genes in a single experiment. As a new technology, Microarray data presents some fresh challenges to scientists since Microarray data contains a large number of genes (around tens thousands) with a small number of samples (around hundreds). Both filter and wrapper gene selection methods aim to select the most informative genes among the massive data in order to reduce the size of the expression database. Gene selection methods are used in both data preprocessing and classification stages. We have conducted some experiments on different existing gene selection methods to preprocess Microarray data for classification by benchmark algorithms SVMs and C4.5. The study suggests that the combination of filter and wrapper methods in general improve the accuracy performance of gene expression Microarray data classification. The study also indicates that not all filter gene selection methods help improve the performance of classification. The experimental results show that among tested gene selection methods, Correlation Coefficient is the best gene selection method for improving the classification accuracy on both SVMs and C4.5 classification algorithms

Simultaneous Relevant Feature Identification and Classification in High-Dimensional Spaces

Molecular profiling technologies monitor thousands of transcripts, proteins, metabolites or other species concurrently in biological samples of interest. Given two-class, high-dimensional profiling data, nominal Liknon [4] is a specific implementation of a methodology for performing simultaneous relevant feature identification and classification. It exploits the well-known property that minimising an l_1 norm (via linear programming) yields a sparse hyperplane [15, 26, 2, 8, 17]. This work (i) examines computational, software and practical issues required to realise nominal Liknon, (ii) summarises results from its application to five real world data sets, (iii) outlines heuristic solutions to problems posed by domain experts when interpreting the results and (iv) defines some future directions of the research