TiGER: A database for tissue-specific gene expression and regulation

Liu, Xiong; Yu, Xueping; Zack, Donald J.; Zhu, Heng; Qian, Jiang

doi:10.1186/1471-2105-9-271

Cited by 367 publications

(328 citation statements)

References 16 publications

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“…This analysis revealed that a few cell lines, previously thought to be unrelated, were derived from the same patient (Supplementary Data 1). Global mRNA expression profiling was carried out on the entire cell bank and TiGER (tissue-specific gene expression database) 13 was exploited to perform a 'tissue of origin' analysis ( Supplementary Fig. 1a).…”

Section: Resultsmentioning

confidence: 99%

“…Thirty panels of genes with tissue-specific expression were retrieved from the TIGER portal 13 (http://bioinfo.wilmer.jhu.edu/tiger/) and filtered to remove gene symbol redundancies. Similarly, to avoid probe redundancy in array data, when multiple probes matched the same gene we selected the one with the highest s.d.. For the tissue of origin analysis, we assumed that the vast majority of the cell lines present in this data set were of colorectal origin, while only a very small fraction could possibly derive from other tissues.…”

Section: Articlementioning

confidence: 99%

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The molecular landscape of colorectal cancer cell lines unveils clinically actionable kinase targets

et al. 2015

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The development of molecularly targeted anticancer agents relies on large panels of tumourspecific preclinical models closely recapitulating the molecular heterogeneity observed in patients. Here we describe the mutational and gene expression analyses of 151 colorectal cancer (CRC) cell lines. We find that the whole spectrum of CRC molecular and transcriptional subtypes, previously defined in patients, is represented in this cell line compendium. Transcriptional outlier analysis identifies RAS/BRAF wild-type cells, resistant to EGFR blockade, functionally and pharmacologically addicted to kinase genes including ALK, FGFR2, NTRK1/2 and RET. The same genes are present as expression outliers in CRC patient samples. Genomic rearrangements (translocations) involving the ALK and NTRK1 genes are associated with the overexpression of the corresponding proteins in CRC specimens. The approach described here can be used to pinpoint CRCs with exquisite dependencies to individual kinases for which clinically approved drugs are already available.

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Section: Resultsmentioning

confidence: 99%

Section: Articlementioning

confidence: 99%

The molecular landscape of colorectal cancer cell lines unveils clinically actionable kinase targets

et al. 2015

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“…We made the same observation even at the whole-genome level, using the National Center for Biotechnology Information reference sequences: CpG-poor promoters were enriched in more hypomethylated DMRs (671 of 16,631) in the centenarian vs. the newborn compared with the annotated CpG island promoters (585 of 23,139) (χ 2 test, P < 3.1 × 10 −16 ). We also analyzed the DMR data with respect to the expression profile of the associated genes obtained from the tissue-specific gene expression and regulation (TiGER) database (27). Considering the expression profile, genes with restricted tissue-specific expression more commonly had DMR hypomethylated sequences in the Y103 sample vs. the NB sample (87%, 56 of 64) than did housekeeping genes (66%, 1,200 of 1,811) (χ 2 test, P < 6.4 × 10 −4 ) (Fig.…”

Section: −16mentioning

confidence: 99%

Distinct DNA methylomes of newborns and centenarians

Heyn

Ferreira

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

711

602

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Human aging cannot be fully understood in terms of the constrained genetic setting. Epigenetic drift is an alternative means of explaining age-associated alterations. To address this issue, we performed whole-genome bisulfite sequencing (WGBS) of newborn and centenarian genomes. The centenarian DNA had a lower DNA methylation content and a reduced correlation in the methylation status of neighboring cytosine-phosphate-guanine (CpGs) throughout the genome in comparison with the more homogeneously methylated newborn DNA. The more hypomethylated CpGs observed in the centenarian DNA compared with the neonate covered all genomic compartments, such as promoters, exonic, intronic, and intergenic regions. For regulatory regions, the most hypomethylated sequences in the centenarian DNA were present mainly at CpG-poor promoters and in tissue-specific genes, whereas a greater level of DNA methylation was observed in CpG island promoters. We extended the study to a larger cohort of newborn and nonagenarian samples using a 450,000 CpG-site DNA methylation microarray that reinforced the observation of more hypomethylated DNA sequences in the advanced age group. WGBS and 450,000 analyses of middle-age individuals demonstrated DNA methylomes in the crossroad between the newborn and the nonagenarian/centenarian groups. Our study constitutes a unique DNA methylation analysis of the extreme points of human life at a single-nucleotide resolution level.epigenomics | longevity D uring human aging, progressive impairment of organ and tissue functionality leads to an increasing probability of death. The molecular culprits behind this decline in physiological activities remain largely unknown. Studies of transcriptional and genomic associations in distinct tissues have identified several gene families and cellular pathways that might contribute to aging and alter lifespan. These families include the Sirtuins, DNA repair enzymes, insulin-signaling pathway/forkhead transcription factors, apolipoproteins, telomere biology, and oxidative damage/ mitochondrial metabolism (1, 2). Aging-associated mechanisms apparently involve many networks within a given cell. Considering that epigenetic regulation has emerged as a critical driver of cell fate and survival that targets many pathways (3, 4), that epigenetic drift can occur even in genetically identical humans (5, 6), and that DNA methylation patterns are disrupted in a wide range of common human diseases (7-11), we wondered whether individuals at the most extreme points of their lifespan had different DNA methylomes. To address this issue, we used whole-genome bisulfite sequencing (WGBS) (12-16) and a 450,000 CpG DNA methylation microarray to examine the DNA methylation profiles of newborn and nonagenarian/centenarian samples.Results and Discussion WGBS of Newborn and Centenarian DNA. The initial data were generated from the cord blood of a newborn (male Caucasian; NB) and from a centenarian (103-y-old male Caucasian; Y103) using DNA extracted from CD4 + T cells processed through an Illumina G...

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“…This added APOB SNP (rs1042034) was not in LD with the other identifi ed APOB SNP ( r 2 = 0.094). We next utilized Tissue-Specifi c Gene Expression and Regulation (TIGER) ( 23 ) to examine the tissue expression of these 22 loci to exclude genes not expressed in the stomach, small intestine, or pancreas, with separate confi rmation of nonhepatic gastrointestinal gene expression through the total European Molecular Biology Laboratory (EMBL) Nucleotide Sequence Database ( 24 ). We excluded genes for transcription cholesterol, thereby infl uencing the potential benefi t of lifestyle changes in the prevention of CVD.…”

Section: Snp Selectionmentioning

confidence: 99%

Novel gene-by-environment interactions: APOB and NPC1L1 variants affect the relationship between dietary and total plasma cholesterol

Kim

Burt

Ranchalis

et al. 2013

Journal of Lipid Research

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This article is available online at http://www.jlr.org Supplementary key words dietary cholesterol • total cholesterol • cardiovascular disease • Niemann-Pick C1-like 1 Cardiovascular disease (CVD), including coronary heart disease and carotid artery disease (CAAD), is the leading cause of death in developed countries, accounting for approximately one-third of all deaths in adults over age 35 ( 1 ). One of the key risk factors for CVD is hypercholesterolemia ( 2 ), with epidemiologic studies demonstrating a graded relationship between total plasma cholesterol and CVD risk ( 3 ). Levels of total cholesterol and other lipids and lipoproteins are both heritable and targets for pharmacologic and lifestyle interventions ( 4 ). One of the primary methods of lifestyle intervention to alter lipid levels is through dietary changes, such as decreasing total fat intake ( 5, 6 ).Genome-wide association studies (GWASs) have implicated numerous genetic loci for association with total cholesterol levels. A recent meta-analysis by Teslovich et al. ( 7 ) of over 100,000 individuals of European ancestry confi rmed numerous previous GWAS fi ndings and identifi ed novel variants and loci for prediction of total lipid phenotypes, including total cholesterol levels.While genetic evidence is accumulating for many of these loci, less is known about the specifi c mechanisms through which these genetic variants affect cholesterol levels. We hypothesized that one pathway through which these genetic variants could alter cholesterol homeostasis is through differential absorption or processing of dietary Abstract Cardiovascular disease (CVD) is the leading cause of death in developed countries. Plasma cholesterol level is a key risk factor in CVD pathogenesis. Genetic and dietary variation both infl uence plasma cholesterol; however, little is known about dietary interactions with genetic variants infl uencing the absorption and transport of dietary cholesterol . We sought to determine whether gut expressed variants predicting plasma cholesterol differentially affected the relationship between dietary and plasma cholesterol levels in 1,128 subjects (772/356 in the discovery/replication cohorts, respectively). Four single nucleotide polymorphisms (SNPs) within three genes ( APOB , CETP , and NPC1L1 ) were signifi cantly associated with plasma cholesterol in the discovery cohort. These were subsequently evaluated for geneby-environment (GxE) interactions with dietary cholesterol for the prediction of plasma cholesterol, with signifi cant fi ndings tested for replication. Novel GxE interactions were identifi ed and replicated for two variants: rs1042034, an APOB Ser4338Asn missense SNP and rs2072183 (in males only), a synonymous NPC1L1 SNP in linkage disequilibrium with SNPs 5 ′ of NPC1L1 . This study identifi es the presence of novel GxE and gender interactions implying that differential gut absorption is the basis for the variant associations with plasma cholesterol. These GxE interactions may account for part of the "missing heritability" no...

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TiGER: A database for tissue-specific gene expression and regulation

Cited by 367 publications

References 16 publications

The molecular landscape of colorectal cancer cell lines unveils clinically actionable kinase targets

The molecular landscape of colorectal cancer cell lines unveils clinically actionable kinase targets

Distinct DNA methylomes of newborns and centenarians

Novel gene-by-environment interactions: APOB and NPC1L1 variants affect the relationship between dietary and total plasma cholesterol

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