Project description:Emerging evidence indicates that noncoding RNAs play regulatory roles in aging and disease. The functional roles of long noncoding RNAs (lncRNAs) in physiology and disease are not completely understood. Little is known about lncRNAs in the context of human aging and socio-environmental conditions. Microarray profiling of lncRNAs and mRNAs from peripheral blood mononuclear cells from young and old white (n=16) and African American (AA) males (n=16) living above or below poverty from the Healthy Aging in Neighborhoods of Diversity across the Life Span study revealed changes in both lncRNAs and mRNAs with age and poverty status in white males, but not in AA males. We validated lncRNA changes in an expanded cohort (n=40); CTD-3247F14.2, GAS5, H19, TERC and MEG3 changed significantly with age, whereas AK022914, GAS5, KB-1047C11.2, MEG3 and XLOC_003262 changed with poverty. Mitochondrial function and response to DNA damage and stress were pathways enriched in younger individuals. Response to stress, viral infection, and immune signals were pathways enriched in individuals living above poverty. These data show that both human age and a marker of social adversity influence lncRNA expression, which may provide insight about molecular pathways underlying aging and social factors that affect disparities in aging and disease.
Project description:Emerging evidence indicates that noncoding RNAs play important regulatory roles during aging and the development of chronic disease. The functional roles of long noncoding RNAs (lncRNAs) in physiology and disease are under intense examination. However, little is known about lncRNAs in the context of human aging and socio-environmental conditions. Microarray profiling of lncRNAs and mRNAs in young and old white and African American (AA) males living above or below poverty revealed robust changes in both lncRNAs and mRNAs with age and poverty status in white males, but not in AA males. We validated the changes in lncRNAs in an expanded cohort; CDT-3247F14.2, GAS5, H19, TERC and MEG3 changed significantly with age, whereas AK022914, GAS5, KB-1047C11.2, MEG3 and XLOC_003262 changed significantly with poverty. Pathway analysis revealed that mitochondrial function and response to DNA damage and stress were enriched in younger individuals. Pathways of response to stress, viral infection, and immune signals were enriched in individuals living above poverty. These data show that both human age and a marker of social adversity influence lncRNA expression patterns. These data may provide insight into the molecular pathways underlying aging and social factors that affect disparities in aging and disease.
Project description:Emerging evidence indicates that noncoding RNAs play important regulatory roles during aging and the development of chronic disease. The functional roles of long noncoding RNAs (lncRNAs) in physiology and disease are under intense examination. However, little is known about lncRNAs in the context of human aging and socio-environmental conditions. Microarray profiling of lncRNAs and mRNAs in young and old white and African American (AA) males living above or below poverty revealed robust changes in both lncRNAs and mRNAs with age and poverty status in white males, but not in AA males. We validated the changes in lncRNAs in an expanded cohort; CDT-3247F14.2, GAS5, H19, TERC and MEG3 changed significantly with age, whereas AK022914, GAS5, KB-1047C11.2, MEG3 and XLOC_003262 changed significantly with poverty. Pathway analysis revealed that mitochondrial function and response to DNA damage and stress were enriched in younger individuals. Pathways of response to stress, viral infection, and immune signals were enriched in individuals living above poverty. These data show that both human age and a marker of social adversity influence lncRNA expression patterns. These data may provide insight into the molecular pathways underlying aging and social factors that affect disparities in aging and disease.
Project description:The advent of high-throughput RNA sequencing (RNA-seq) has led to the discovery of unprecedentedly immense transcriptomes encoded by eukaryotic genomes. However, the transcriptome maps are still incomplete partly because they were mostly reconstructed based on RNA-seq reads that lack their orientations (known as unstranded reads) and certain boundary information. Methods to expand the usability of unstranded RNA-seq data by predetermining the orientation of the reads and precisely determining the boundaries of assembled transcripts could significantly benefit the quality of the resulting transcriptome maps. Here, we present a high-performing transcriptome assembly pipeline, called CAFE, that significantly improves the original assemblies, respectively assembled with stranded and/or unstranded RNA-seq data, by orienting unstranded reads using the maximum likelihood estimation and by integrating information about transcription start sites and cleavage and polyadenylation sites. Applying large-scale transcriptomic data comprising 230 billion RNA-seq reads from the ENCODE, Human BodyMap 2.0, The Cancer Genome Atlas, and GTEx projects, CAFE enabled us to predict the directions of about 220 billion unstranded reads, which led to the construction of more accurate transcriptome maps, comparable to the manually curated map, and a comprehensive lncRNA catalog that includes thousands of novel lncRNAs. Our pipeline should not only help to build comprehensive, precise transcriptome maps from complex genomes but also to expand the universe of noncoding genomes.
