A genomic portrait of the genetic architecture and regulatory impact of microRNA expression in response to infection.

Abstract:

:MicroRNAs (miRNAs) are critical regulators of gene expression, and their role in a wide variety of biological processes, including host antimicrobial defense, is increasingly well described. Consistent with their diverse functional effects, miRNA expression is highly context dependent and shows marked changes upon cellular activation. However, the genetic control of miRNA expression in response to external stimuli and the impact of such perturbations on miRNA-mediated regulatory networks at the population level remain to be determined. Here we assessed changes in miRNA expression upon Mycobacterium tuberculosis infection and mapped expression quantitative trait loci (eQTL) in dendritic cells from a panel of healthy individuals. Genome-wide expression profiling revealed that ∼40% of miRNAs are differentially expressed upon infection. We find that the expression of 3% of miRNAs is controlled by proximate genetic factors, which are enriched in a promoter-specific histone modification associated with active transcription. Notably, we identify two infection-specific response eQTLs, for miR-326 and miR-1260, providing an initial assessment of the impact of genotype-environment interactions on miRNA molecular phenotypes. Furthermore, we show that infection coincides with a marked remodeling of the genome-wide relationships between miRNA and mRNA expression levels. This observation, supplemented by experimental data using the model of miR-29a, sheds light on the role of a set of miRNAs in cellular responses to infection. Collectively, this study increases our understanding of the genetic architecture of miRNA expression in response to infection, and highlights the wide-reaching impact of altering miRNA expression on the transcriptional landscape of a cell.

journal_name

Genome Res

journal_title

Genome research

authors

Siddle KJ,Deschamps M,Tailleux L,Nédélec Y,Pothlichet J,Lugo-Villarino G,Libri V,Gicquel B,Neyrolles O,Laval G,Patin E,Barreiro LB,Quintana-Murci L

doi

10.1101/gr.161471.113

subject

Has Abstract

pub_date

2014-05-01 00:00:00

pages

850-9

issue

5

eissn

1088-9051

issn

1549-5469

pii

gr.161471.113

journal_volume

24

pub_type

杂志文章
  • Gene expression profiling of single cells from archival tissue with laser-capture microdissection and Smart-3SEQ.

    abstract::RNA sequencing (RNA-seq) is a sensitive and accurate method for quantifying gene expression. Small samples or those whose RNA is degraded, such as formalin-fixed paraffin-embedded (FFPE) tissue, remain challenging to study with nonspecialized RNA-seq protocols. Here, we present a new method, Smart-3SEQ, that accuratel...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.234807.118

    authors: Foley JW,Zhu C,Jolivet P,Zhu SX,Lu P,Meaney MJ,West RB

    更新日期:2019-11-01 00:00:00

  • HD-Marker: a highly multiplexed and flexible approach for targeted genotyping of more than 10,000 genes in a single-tube assay.

    abstract::Targeted genotyping of transcriptome-scale genetic markers is highly attractive for genetic, ecological, and evolutionary studies, but achieving this goal in a cost-effective manner remains a major challenge, especially for laboratories working on nonmodel organisms. Here, we develop a high-throughput, sequencing-base...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.235820.118

    authors: Lv J,Jiao W,Guo H,Liu P,Wang R,Zhang L,Zeng Q,Hu X,Bao Z,Wang S

    更新日期:2018-12-01 00:00:00

  • A matter of life or death: how microsatellites emerge in and vanish from the human genome.

    abstract::Microsatellites--tandem repeats of short DNA motifs--are abundant in the human genome and have high mutation rates. While microsatellite instability is implicated in numerous genetic diseases, the molecular processes involved in their emergence and disappearance are still not well understood. Microsatellites are hypot...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.122937.111

    authors: Kelkar YD,Eckert KA,Chiaromonte F,Makova KD

    更新日期:2011-12-01 00:00:00

  • Sequence features and chromatin structure around the genomic regions bound by 119 human transcription factors.

    abstract::Chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-seq) has become the dominant technique for mapping transcription factor (TF) binding regions genome-wide. We performed an integrative analysis centered around 457 ChIP-seq data sets on 119 human TFs generated by the ENCODE Consortium. We ident...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.139105.112

    authors: Wang J,Zhuang J,Iyer S,Lin X,Whitfield TW,Greven MC,Pierce BG,Dong X,Kundaje A,Cheng Y,Rando OJ,Birney E,Myers RM,Noble WS,Snyder M,Weng Z

    更新日期:2012-09-01 00:00:00

  • Retrotransposon Ty1 integration targets specifically positioned asymmetric nucleosomal DNA segments in tRNA hotspots.

    abstract::The Saccharomyces cerevisiae genome contains about 35 copies of dispersed retrotransposons called Ty1 elements. Ty1 elements target regions upstream of tRNA genes and other Pol III-transcribed genes when retrotransposing to new sites. We used deep sequencing of Ty1-flanking sequence amplicons to characterize Ty1 integ...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.129460.111

    authors: Mularoni L,Zhou Y,Bowen T,Gangadharan S,Wheelan SJ,Boeke JD

    更新日期:2012-04-01 00:00:00

  • The pig X and Y Chromosomes: structure, sequence, and evolution.

    abstract::We have generated an improved assembly and gene annotation of the pig X Chromosome, and a first draft assembly of the pig Y Chromosome, by sequencing BAC and fosmid clones from Duroc animals and incorporating information from optical mapping and fiber-FISH. The X Chromosome carries 1033 annotated genes, 690 of which a...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.188839.114

    authors: Skinner BM,Sargent CA,Churcher C,Hunt T,Herrero J,Loveland JE,Dunn M,Louzada S,Fu B,Chow W,Gilbert J,Austin-Guest S,Beal K,Carvalho-Silva D,Cheng W,Gordon D,Grafham D,Hardy M,Harley J,Hauser H,Howden P,Howe K,

    更新日期:2016-01-01 00:00:00

  • A fine scale phenotype-genotype virulence map of a bacterial pathogen.

    abstract::A large fraction of the genes from sequenced organisms are of unknown function. This limits biological insight, and for pathogenic microorganisms hampers the development of new approaches to battle infections. There is thus a great need for novel strategies that link genotypes to phenotypes for microorganisms. We desc...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.137430.112

    authors: van Opijnen T,Camilli A

    更新日期:2012-12-01 00:00:00

  • Copy number variation at the breakpoint region of isochromosome 17q.

    abstract::Isochromosome 17q, or i(17q), is one of the most frequent nonrandom changes occurring in human neoplasia. Most of the i(17q) breakpoints cluster within a approximately 240-kb interval located in the Smith-Magenis syndrome common deletion region in 17p11.2. The breakpoint cluster region is characterized by a complex ar...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.080697.108

    authors: Carvalho CM,Lupski JR

    更新日期:2008-11-01 00:00:00

  • A combinatorial partitioning method to identify multilocus genotypic partitions that predict quantitative trait variation.

    abstract::Recent advances in genome research have accelerated the process of locating candidate genes and the variable sites within them and have simplified the task of genotype measurement. The development of statistical and computational strategies to utilize information on hundreds -- soon thousands -- of variable loci to in...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.172901

    authors: Nelson MR,Kardia SL,Ferrell RE,Sing CF

    更新日期:2001-03-01 00:00:00

  • A platform for curated products from novel open reading frames prompts reinterpretation of disease variants.

    abstract::Recent evidence from proteomics and deep massively parallel sequencing studies have revealed that eukaryotic genomes contain substantial numbers of as-yet-uncharacterized open reading frames (ORFs). We define these uncharacterized ORFs as novel ORFs (nORFs). nORFs in humans are mostly under 100 codons and are found in...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.263202.120

    authors: Neville MDC,Kohze R,Erady C,Meena N,Hayden M,Cooper DN,Mort M,Prabakaran S

    更新日期:2021-01-19 00:00:00

  • lobSTR: A short tandem repeat profiler for personal genomes.

    abstract::Short tandem repeats (STRs) have a wide range of applications, including medical genetics, forensics, and genetic genealogy. High-throughput sequencing (HTS) has the potential to profile hundreds of thousands of STR loci. However, mainstream bioinformatics pipelines are inadequate for the task. These pipelines treat S...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.135780.111

    authors: Gymrek M,Golan D,Rosset S,Erlich Y

    更新日期:2012-06-01 00:00:00

  • A first-generation whole genome-radiation hybrid map spanning the mouse genome.

    abstract::We have assembled a first-generation anchor map of the mouse genome using a panel of 94 whole-genome-radiation hybrids (WG-RHs) and 271 sequence-tagged sites (STSs). This is the first genome-wide RH anchor map of a model organism. All of the STSs have been previously localized on the genetic map and are located 8.8 Mb...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.7.12.1153

    authors: McCarthy LC,Terrett J,Davis ME,Knights CJ,Smith AL,Critcher R,Schmitt K,Hudson J,Spurr NK,Goodfellow PN

    更新日期:1997-12-01 00:00:00

  • Bacterial genomes as new gene homes: the genealogy of ORFans in E. coli.

    abstract::Differences in gene repertoire among bacterial genomes are usually ascribed to gene loss or to lateral gene transfer from unrelated cellular organisms. However, most bacteria contain large numbers of ORFans, that is, annotated genes that are restricted to a particular genome and that possess no known homologs. The uni...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.2231904

    authors: Daubin V,Ochman H

    更新日期:2004-06-01 00:00:00

  • Gene-specific vulnerability to imprinting variability in human embryonic stem cell lines.

    abstract::Disregulation of imprinted genes can be associated with tumorigenesis and altered cell differentiation capacity and so could provide adverse outcomes for stem cell applications. Although the maintenance of mouse and primate embryonic stem cells in a pluripotent state has been reported to disrupt the monoallelic expres...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.6609207

    authors: Kim KP,Thurston A,Mummery C,Ward-van Oostwaard D,Priddle H,Allegrucci C,Denning C,Young L

    更新日期:2007-12-01 00:00:00

  • SNP-based quantitative deconvolution of biological mixtures: application to the detection of cows with subclinical mastitis by whole-genome sequencing of tank milk.

    abstract::Biological products of importance in food (e.g., milk) and medical (e.g., donor blood-derived products) sciences often correspond to mixtures of samples contributed by multiple individuals. Identifying which individuals contributed to the mixture and in what proportions may be of interest in several circumstances. We ...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.256172.119

    authors: Coppieters W,Karim L,Georges M

    更新日期:2020-08-01 00:00:00

  • Integrative functional genomics identifies an enhancer looping to the SOX9 gene disrupted by the 17q24.3 prostate cancer risk locus.

    abstract::Genome-wide association studies (GWAS) are identifying genetic predisposition to various diseases. The 17q24.3 locus harbors the single nucleotide polymorphism (SNP) rs1859962 that is statistically associated with prostate cancer (PCa). It defines a 130-kb linkage disequilibrium (LD) block that lies in an ∼2-Mb gene d...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.135665.111

    authors: Zhang X,Cowper-Sal lari R,Bailey SD,Moore JH,Lupien M

    更新日期:2012-08-01 00:00:00

  • Ancestry-agnostic estimation of DNA sample contamination from sequence reads.

    abstract::Detecting and estimating DNA sample contamination are important steps to ensure high-quality genotype calls and reliable downstream analysis. Existing methods rely on population allele frequency information for accurate estimation of contamination rates. Correctly specifying population allele frequencies for each indi...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.246934.118

    authors: Zhang F,Flickinger M,Taliun SAG,InPSYght Psychiatric Genetics Consortium.,Abecasis GR,Scott LJ,McCaroll SA,Pato CN,Boehnke M,Kang HM

    更新日期:2020-02-01 00:00:00

  • Inference of population genetic parameters in metagenomics: a clean look at messy data.

    abstract::Metagenomic projects generate short, overlapping fragments of DNA sequence, each deriving from a different individual. We report a new method for inferring the scaled mutation rate, theta = 2Neu, and the scaled exponential growth rate, R = Ner, from the site-frequency spectrum of these data while accounting for sequen...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.5431206

    authors: Johnson PL,Slatkin M

    更新日期:2006-10-01 00:00:00

  • Transposon expression in the Drosophila brain is driven by neighboring genes and diversifies the neural transcriptome.

    abstract::Somatic transposon expression in neural tissue is commonly considered as a measure of mobilization and has therefore been linked to neuropathology and organismal individuality. We combined genome sequencing data with single-cell mRNA sequencing of the same inbred fly strain to map transposon expression in the Drosophi...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.259200.119

    authors: Treiber CD,Waddell S

    更新日期:2020-11-01 00:00:00

  • Genomic analysis identifies association of Fusobacterium with colorectal carcinoma.

    abstract::The tumor microenvironment of colorectal carcinoma is a complex community of genomically altered cancer cells, nonneoplastic cells, and a diverse collection of microorganisms. Each of these components may contribute to carcinogenesis; however, the role of the microbiota is the least well understood. We have characteri...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.126573.111

    authors: Kostic AD,Gevers D,Pedamallu CS,Michaud M,Duke F,Earl AM,Ojesina AI,Jung J,Bass AJ,Tabernero J,Baselga J,Liu C,Shivdasani RA,Ogino S,Birren BW,Huttenhower C,Garrett WS,Meyerson M

    更新日期:2012-02-01 00:00:00

  • Why do human diversity levels vary at a megabase scale?

    abstract::Levels of diversity vary across the human genome. This variation is caused by two forces: differences in mutation rates and the differential impact of natural selection. Pertinent to the question of the relative importance of these two forces is the observation that both diversity within species and interspecies diver...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.3461105

    authors: Hellmann I,Prüfer K,Ji H,Zody MC,Pääbo S,Ptak SE

    更新日期:2005-09-01 00:00:00

  • Novel noncoding RNA from human Y distal heterochromatic block (Yq12) generates testis-specific chimeric CDC2L2.

    abstract::The human Y chromosome, because it is enriched in repetitive DNA, has been very intractable to genetic and molecular analyses. There is no previous evidence for developmental stage- and testis-specific transcription from the male-specific region of the Y (MSY). Here, we present evidence for the first time for a develo...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.5155706

    authors: Jehan Z,Vallinayagam S,Tiwari S,Pradhan S,Singh L,Suresh A,Reddy HM,Ahuja YR,Jesudasan RA

    更新日期:2007-04-01 00:00:00

  • From first base: the sequence of the tip of the X chromosome of Drosophila melanogaster, a comparison of two sequencing strategies.

    abstract::We present the sequence of a contiguous 2.63 Mb of DNA extending from the tip of the X chromosome of Drosophila melanogaster. Within this sequence, we predict 277 protein coding genes, of which 94 had been sequenced already in the course of studying the biology of their gene products, and examples of 12 different tran...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.173801

    authors: Benos PV,Gatt MK,Murphy L,Harris D,Barrell B,Ferraz C,Vidal S,Brun C,Demaille J,Cadieu E,Dreano S,Gloux S,Lelaure V,Mottier S,Galibert F,Borkova D,Miñana B,Kafatos FC,Bolshakov S,Sidén-Kiamos I,Papagiannakis G,S

    更新日期:2001-05-01 00:00:00

  • End Sequence Analysis Toolkit (ESAT) expands the extractable information from single-cell RNA-seq data.

    abstract::RNA-seq protocols that focus on transcript termini are well suited for applications in which template quantity is limiting. Here we show that, when applied to end-sequencing data, analytical methods designed for global RNA-seq produce computational artifacts. To remedy this, we created the End Sequence Analysis Toolki...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.207902.116

    authors: Derr A,Yang C,Zilionis R,Sergushichev A,Blodgett DM,Redick S,Bortell R,Luban J,Harlan DM,Kadener S,Greiner DL,Klein A,Artyomov MN,Garber M

    更新日期:2016-10-01 00:00:00

  • A non-EST-based method for exon-skipping prediction.

    abstract::It is estimated that between 35% and 74% of all human genes can undergo alternative splicing. Currently, the most efficient methods for large-scale detection of alternative splicing use expressed sequence tags (ESTs) or microarray analysis. As these methods merely sample the transcriptome, splice variants that do not ...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.2572604

    authors: Sorek R,Shemesh R,Cohen Y,Basechess O,Ast G,Shamir R

    更新日期:2004-08-01 00:00:00

  • The Arabidopsis genome: a foundation for plant research.

    abstract::The sequence of the first plant genome was completed and published at the end of 2000. This spawned a series of large-scale projects aimed at discovering the functions of the 25,000+ genes identified in Arabidopsis thaliana (Arabidopsis). This review summarizes progress made in the past five years and speculates about...

    journal_title:Genome research

    pub_type: 杂志文章,评审

    doi:10.1101/gr.3723405

    authors: Bevan M,Walsh S

    更新日期:2005-12-01 00:00:00

  • Genome-wide map of regulatory interactions in the human genome.

    abstract::Increasing evidence suggests that interactions between regulatory genomic elements play an important role in regulating gene expression. We generated a genome-wide interaction map of regulatory elements in human cells (ENCODE tier 1 cells, K562, GM12878) using Chromatin Interaction Analysis by Paired-End Tag sequencin...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.176586.114

    authors: Heidari N,Phanstiel DH,He C,Grubert F,Jahanbani F,Kasowski M,Zhang MQ,Snyder MP

    更新日期:2014-12-01 00:00:00

  • Detection of numerous Y chromosome biallelic polymorphisms by denaturing high-performance liquid chromatography.

    abstract::Y chromosome haplotypes are particularly useful in deciphering human evolutionary history because they accentuate the effects of drift, migration, and range expansion. Significant acceleration of Y biallelic marker discovery and subsequent typing involving heteroduplex detection has been achieved by implementing an in...

    journal_title:Genome research

    pub_type: 信件

    doi:10.1101/gr.7.10.996

    authors: Underhill PA,Jin L,Lin AA,Mehdi SQ,Jenkins T,Vollrath D,Davis RW,Cavalli-Sforza LL,Oefner PJ

    更新日期:1997-10-01 00:00:00

  • The use of exome capture RNA-seq for highly degraded RNA with application to clinical cancer sequencing.

    abstract::RNA-seq by poly(A) selection is currently the most common protocol for whole transcriptome sequencing as it provides a broad, detailed, and accurate view of the RNA landscape. Unfortunately, the utility of poly(A) libraries is greatly limited when the input RNA is degraded, which is the norm for research tissues and c...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.189621.115

    authors: Cieslik M,Chugh R,Wu YM,Wu M,Brennan C,Lonigro R,Su F,Wang R,Siddiqui J,Mehra R,Cao X,Lucas D,Chinnaiyan AM,Robinson D

    更新日期:2015-09-01 00:00:00

  • Interaction between the X chromosome and an autosome regulates size sexual dimorphism in Portuguese Water Dogs.

    abstract::Size sexual dimorphism occurs in almost all mammals. In Portuguese Water Dogs, much of the difference in skeletal size between females and males is due to the interaction between a Quantitative Trait Locus (QTL) on the X-chromosome and a QTL linked to Insulin-like Growth Factor 1 (IGF-1) on the CFA 15 autosome. In fem...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.3712705

    authors: Chase K,Carrier DR,Adler FR,Ostrander EA,Lark KG

    更新日期:2005-12-01 00:00:00