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Articles 1 - 5 of 5
Full-Text Articles in Life Sciences
Transcriptome Prediction Performance Across Machine Learning Models And Diverse Ancestries, Paul Chukwuebuka Okoro, Ryan Schubert, Xiuqing Guo, W. Craig Johnson, Jerome I. Rotter, Ina Hoeschele, Yongmei Liu, Hae Kyung Im, Amy Luke, Lara R. Dugas, Heather Wheeler
Transcriptome Prediction Performance Across Machine Learning Models And Diverse Ancestries, Paul Chukwuebuka Okoro, Ryan Schubert, Xiuqing Guo, W. Craig Johnson, Jerome I. Rotter, Ina Hoeschele, Yongmei Liu, Hae Kyung Im, Amy Luke, Lara R. Dugas, Heather Wheeler
Biology: Faculty Publications and Other Works
Transcriptome prediction methods such as PrediXcan and FUSION have become popular in complex trait mapping. Most transcriptome prediction models have been trained in European populations using methods that make parametric linear assumptions like the elastic net (EN). To potentially further optimize imputation performance of gene expression across global populations, we built transcriptome prediction models using both linear and non-linear machine learning (ML) algorithms and evaluated their performance in comparison to EN. We trained models using genotype and blood monocyte transcriptome data from the Multi-Ethnic Study of Atherosclerosis (MESA) comprising individuals of African, Hispanic, and European ancestries and tested them using …
A High-Fat Diet Alters Genome-Wide Dna Methylation And Gene Expression In Sm/J Mice, Madeline R. Keleher, Rabab Zaidi, Lauren Hicks, Shyam Shah, Xiaoyun Xing, Daofeng Li, Ting Wang, James M. Cheverud
A High-Fat Diet Alters Genome-Wide Dna Methylation And Gene Expression In Sm/J Mice, Madeline R. Keleher, Rabab Zaidi, Lauren Hicks, Shyam Shah, Xiaoyun Xing, Daofeng Li, Ting Wang, James M. Cheverud
Biology: Faculty Publications and Other Works
Background: While the genetics of obesity has been well defined, the epigenetics of obesity is poorly understood. Here, we used a genome-wide approach to identify genes with differences in both DNA methylation and expression associated with a high-fat diet in mice. Results: We weaned genetically identical Small (SM/J) mice onto a high-fat or low-fat diet and measured their weights weekly, tested their glucose and insulin tolerance, assessed serum biomarkers, and weighed their organs at necropsy. We measured liver gene expression with RNA-seq (using 21 total libraries, each pooled with 2 mice of the same sex and diet) and DNA methylation …
Genetic And Transcriptional Analysis Of Human Host Response To Healthy Gut Microbiota, Michael B. Burns, Allison L. Richards, Adnan Alazizi, Luis B. Barreiro, Roger Pique-Regi, Ran Blekhman, Francesca Luca
Genetic And Transcriptional Analysis Of Human Host Response To Healthy Gut Microbiota, Michael B. Burns, Allison L. Richards, Adnan Alazizi, Luis B. Barreiro, Roger Pique-Regi, Ran Blekhman, Francesca Luca
Biology: Faculty Publications and Other Works
Many studies have demonstrated the importance of the gut microbiota in healthy and disease states. However, establishing the causality of host-microbiota interactions in humans is still challenging. Here, we describe a novel experimental system to define the transcriptional response induced by the microbiota for human cells and to shed light on the molecular mechanisms underlying host-gut microbiota interactions. In primary human colonic epithelial cells, we identified over 6,000 genes whose expression changed at various time points following coculturing with the gut microbiota of a healthy individual. Among the differentially expressed genes we found a 1.8-fold enrichment of genes associated with …
The Role Of Microrna In Cardioprotection: Ischemic Preconditioning And Mesenchymal Stem Cell Paracrine Effects, Kristin Luther
The Role Of Microrna In Cardioprotection: Ischemic Preconditioning And Mesenchymal Stem Cell Paracrine Effects, Kristin Luther
Dissertations
Changes in gene expression and protein levels are an important aspect of cardioprotection in which short non-coding RNA known as miRNA may play a key regulatory role. We investigated the functions of several miRNAs in the context of two cardioprotective stimuli, ischemic preconditioning (IPC) and mesenchymal stem cell (MSC) paracrine effects. We hypothesized that downregulation of a set of miRNAs (miR-148a/b, miR-30b, and let-7a*) augments expression of protective heat shock proteins during IPC, and that MSC exosomes transfer miR-21 to cardiomyocytes, resulting in downregulation of pro-apoptotic genes and reduction of infarct size.
IPC increased the level of Hsp70, Hsp90, and …
A Gene-Based Association Method For Mapping Traits Using Reference Transcriptome Data, Eric R. Gamazon, Heather Wheeler, Kaanan P. Shah, Sahar V. Mozaffari, Keston Aquino-Michaels, Robert J. Carroll, Anne E. Eyler, Joshua C. Denny, Gtex Consortium, Dan L. Nicolae, Nancy J. Cox, Hae Kyung Im
A Gene-Based Association Method For Mapping Traits Using Reference Transcriptome Data, Eric R. Gamazon, Heather Wheeler, Kaanan P. Shah, Sahar V. Mozaffari, Keston Aquino-Michaels, Robert J. Carroll, Anne E. Eyler, Joshua C. Denny, Gtex Consortium, Dan L. Nicolae, Nancy J. Cox, Hae Kyung Im
Bioinformatics Faculty Publications
Genome-wide association studies (GWAS) have identified thousands of variants robustly associated with complex traits. However, the biological mechanisms underlying these associations are, in general, not well understood. We propose a gene-based association method called PrediXcan that directly tests the molecular mechanisms through which genetic variation affects phenotype. The approach estimates the component of gene expression determined by an individual’s genetic profile and correlates ‘imputed’ gene expression with the phenotype under investigation to identify genes involved in the etiology of the phenotype. Genetically regulated gene expression is estimated using whole-genome tissue-dependent prediction models trained with reference transcriptome data sets. PrediXcan enjoys …