Gaffney Group | Genomics of gene regulation

Gaffney Group | Genomics of gene regulation

Gaffney Group

gaffney-group.jpgSanger Institute, Genome Research Limited

Our Research and Approach

The genomics of gene regulation group is interested in understanding the role of gene regulatory variation in human disease and evolution.

Headed by Daniel Gaffney, the group combines computational and statistical methods with high-throughput experimental techniques to understand the role played by changes in gene regulation in disease susceptibility and human evolution. We are currently involved in both the data generation and analysis of molecular phenotypes in human induced pluripotent stem cells as part of the Human Induced Pluripotent Stem Cells Initiative

The team aims to understand how genetic changes affect the level, location and timing of gene expression using a combination of experimental and computational methods. We are particularly focussed on understanding this variation in pluripotent stem cells as a model of human disease and development.

We welcome applications from prospective postdocs and PhD students. Projects are available in the areas of genomics of gene regulation, molecular evolution and on population genomics of gene regulation. All our work involves data analysis, but there is also scope for projects with a component of laboratory work. Interested applicants should send a CV to Dan (see profile page for contact details), with information on your research, publications and contact details for three references.

For more information, please click "Read more" below.

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People

Dr Daniel Gaffney
Group Leader

Daniel Gaffney's research focusses on identifying genetic changes that alter cell phenotypes and functions. His research combines a mixture of computational and experimental techniques to map and characterise genetic variants that alter cellular traits.

Key Projects, Collaborations, Tools & Data

Our work involves multiple collaborations with groups on and off campus.

Research Programmes

Partners and Funders

Internal Partners
External Partners and Funders

Publications

  • Common genetic variation drives molecular heterogeneity in human iPSCs.

    Kilpinen H, Goncalves A, Leha A, Afzal V, Alasoo K et al.

    Nature 2017;546;7658;370-375

  • Fine-mapping cellular QTLs with RASQUAL and ATAC-seq.

    Kumasaka N, Knights AJ and Gaffney DJ

    Nature genetics 2016;48;2;206-13

  • Transcriptional profiling of macrophages derived from monocytes and iPS cells identifies a conserved response to LPS and novel alternative transcription.

    Alasoo K, Martinez FO, Hale C, Gordon S, Powrie F et al.

    Scientific reports 2015;5;12524

  • Genetic background drives transcriptional variation in human induced pluripotent stem cells.

    Rouhani F, Kumasaka N, de Brito MC, Bradley A, Vallier L and Gaffney D

    PLoS genetics 2014;10;6;e1004432

  • Global properties and functional complexity of human gene regulatory variation.

    Gaffney DJ

    PLoS genetics 2013;9;5;e1003501

  • Controls of nucleosome positioning in the human genome.

    Gaffney DJ, McVicker G, Pai AA, Fondufe-Mittendorf YN, Lewellen N et al.

    PLoS genetics 2012;8;11;e1003036

  • Activin/nodal signaling and NANOG orchestrate human embryonic stem cell fate decisions by controlling the H3K4me3 chromatin mark.

    Bertero A, Madrigal P, Galli A, Hubner NC, Moreno I et al.

    Genes & development 2015;29;7;702-17

  • Epithelial IL-22RA1-mediated fucosylation promotes intestinal colonization resistance to an opportunistic pathogen.

    Pham TA, Clare S, Goulding D, Arasteh JM, Stares MD et al.

    Cell host & microbe 2014;16;4;504-16

  • AHT-ChIP-seq: a completely automated robotic protocol for high-throughput chromatin immunoprecipitation.

    Aldridge S, Watt S, Quail MA, Rayner T, Lukk M et al.

    Genome biology 2013;14;11;R124

  • The contribution of RNA decay quantitative trait loci to inter-individual variation in steady-state gene expression levels.

    Pai AA, Cain CE, Mizrahi-Man O, De Leon S, Lewellen N et al.

    PLoS genetics 2012;8;10;e1003000

  • Dense fine-mapping study identifies new susceptibility loci for primary biliary cirrhosis.

    Liu JZ, Almarri MA, Gaffney DJ, Mells GF, Jostins L et al.

    Nature genetics 2012;44;10;1137-41

  • DNA sequence-dependent compartmentalization and silencing of chromatin at the nuclear lamina.

    Zullo JM, Demarco IA, Piqué-Regi R, Gaffney DJ, Epstein CB et al.

    Cell 2012;149;7;1474-87

  • Exon-specific QTLs skew the inferred distribution of expression QTLs detected using gene expression array data.

    Veyrieras JB, Gaffney DJ, Pickrell JK, Gilad Y, Stephens M and Pritchard JK

    PloS one 2012;7;2;e30629

  • DNase I sensitivity QTLs are a major determinant of human expression variation.

    Degner JF, Pai AA, Pique-Regi R, Veyrieras JB, Gaffney DJ et al.

    Nature 2012;482;7385;390-4

  • Dissecting the regulatory architecture of gene expression QTLs.

    Gaffney DJ, Veyrieras JB, Degner JF, Pique-Regi R, Pai AA et al.

    Genome biology 2012;13;1;R7

  • False positive peaks in ChIP-seq and other sequencing-based functional assays caused by unannotated high copy number regions.

    Pickrell JK, Gaffney DJ, Gilad Y and Pritchard JK

    Bioinformatics (Oxford, England) 2011;27;15;2144-6

  • DNA methylation patterns associate with genetic and gene expression variation in HapMap cell lines.

    Bell JT, Pai AA, Pickrell JK, Gaffney DJ, Pique-Regi R et al.

    Genome biology 2011;12;1;R10

  • Accurate inference of transcription factor binding from DNA sequence and chromatin accessibility data.

    Pique-Regi R, Degner JF, Pai AA, Gaffney DJ, Gilad Y and Pritchard JK

    Genome research 2011;21;3;447-55

  • Alternative splicing is frequent during early embryonic development in mouse.

    Revil T, Gaffney D, Dias C, Majewski J and Jerome-Majewska LA

    BMC genomics 2010;11;399

  • Effect of the assignment of ancestral CpG state on the estimation of nucleotide substitution rates in mammals.

    Gaffney DJ and Keightley PD

    BMC evolutionary biology 2008;8;265

  • Selective constraints in experimentally defined primate regulatory regions.

    Gaffney DJ, Blekhman R and Majewski J

    PLoS genetics 2008;4;8;e1000157

  • Genomic selective constraints in murid noncoding DNA.

    Gaffney DJ and Keightley PD

    PLoS genetics 2006;2;11;e204

  • The scale of mutational variation in the murid genome.

    Gaffney DJ and Keightley PD

    Genome research 2005;15;8;1086-94

  • Functional constraints and frequency of deleterious mutations in noncoding DNA of rodents.

    Keightley PD and Gaffney DJ

    Proceedings of the National Academy of Sciences of the United States of America 2003;100;23;13402-6

  • Common genetic variation drives molecular heterogeneity in human iPSCs.

    Kilpinen H, Goncalves A, Leha A, Afzal V, Alasoo K et al.

    Nature 2017;546;7658;370-375

  • Fine-mapping cellular QTLs with RASQUAL and ATAC-seq.

    Kumasaka N, Knights AJ and Gaffney DJ

    Nature genetics 2016;48;2;206-13

  • A survey of best practices for RNA-seq data analysis.

    Conesa A, Madrigal P, Tarazona S, Gomez-Cabrero D, Cervera A et al.

    Genome biology 2016;17;13

  • Early maturation and distinct tau pathology in induced pluripotent stem cell-derived neurons from patients with MAPT mutations.

    Iovino M, Agathou S, González-Rueda A, Del Castillo Velasco-Herrera M, Borroni B et al.

    Brain : a journal of neurology 2015;138;Pt 11;3345-59

  • Transcriptional profiling of macrophages derived from monocytes and iPS cells identifies a conserved response to LPS and novel alternative transcription.

    Alasoo K, Martinez FO, Hale C, Gordon S, Powrie F et al.

    Scientific reports 2015;5;12524

  • Activin/nodal signaling and NANOG orchestrate human embryonic stem cell fate decisions by controlling the H3K4me3 chromatin mark.

    Bertero A, Madrigal P, Galli A, Hubner NC, Moreno I et al.

    Genes & development 2015;29;7;702-17

  • Epithelial IL-22RA1-mediated fucosylation promotes intestinal colonization resistance to an opportunistic pathogen.

    Pham TA, Clare S, Goulding D, Arasteh JM, Stares MD et al.

    Cell host & microbe 2014;16;4;504-16

  • Genetic background drives transcriptional variation in human induced pluripotent stem cells.

    Rouhani F, Kumasaka N, de Brito MC, Bradley A, Vallier L and Gaffney D

    PLoS genetics 2014;10;6;e1004432

  • AHT-ChIP-seq: a completely automated robotic protocol for high-throughput chromatin immunoprecipitation.

    Aldridge S, Watt S, Quail MA, Rayner T, Lukk M et al.

    Genome biology 2013;14;11;R124

  • Global properties and functional complexity of human gene regulatory variation.

    Gaffney DJ

    PLoS genetics 2013;9;5;e1003501

  • Dense fine-mapping study identifies new susceptibility loci for primary biliary cirrhosis.

    Liu JZ, Almarri MA, Gaffney DJ, Mells GF, Jostins L et al.

    Nature genetics 2012;44;10;1137-41

  • DNA sequence-dependent compartmentalization and silencing of chromatin at the nuclear lamina.

    Zullo JM, Demarco IA, Piqué-Regi R, Gaffney DJ, Epstein CB et al.

    Cell 2012;149;7;1474-87

  • DNase I sensitivity QTLs are a major determinant of human expression variation.

    Degner JF, Pai AA, Pique-Regi R, Veyrieras JB, Gaffney DJ et al.

    Nature 2012;482;7385;390-4

  • Dissecting the regulatory architecture of gene expression QTLs.

    Gaffney DJ, Veyrieras JB, Degner JF, Pique-Regi R, Pai AA et al.

    Genome biology 2012;13;1;R7

  • The contribution of RNA decay quantitative trait loci to inter-individual variation in steady-state gene expression levels.

    Pai AA, Cain CE, Mizrahi-Man O, De Leon S, Lewellen N et al.

    PLoS genetics 2012;8;10;e1003000

  • Controls of nucleosome positioning in the human genome.

    Gaffney DJ, McVicker G, Pai AA, Fondufe-Mittendorf YN, Lewellen N et al.

    PLoS genetics 2012;8;11;e1003036

  • Exon-specific QTLs skew the inferred distribution of expression QTLs detected using gene expression array data.

    Veyrieras JB, Gaffney DJ, Pickrell JK, Gilad Y, Stephens M and Pritchard JK

    PloS one 2012;7;2;e30629

  • False positive peaks in ChIP-seq and other sequencing-based functional assays caused by unannotated high copy number regions.

    Pickrell JK, Gaffney DJ, Gilad Y and Pritchard JK

    Bioinformatics (Oxford, England) 2011;27;15;2144-6

  • Accurate inference of transcription factor binding from DNA sequence and chromatin accessibility data.

    Pique-Regi R, Degner JF, Pai AA, Gaffney DJ, Gilad Y and Pritchard JK

    Genome research 2011;21;3;447-55

  • DNA methylation patterns associate with genetic and gene expression variation in HapMap cell lines.

    Bell JT, Pai AA, Pickrell JK, Gaffney DJ, Pique-Regi R et al.

    Genome biology 2011;12;1;R10

  • Alternative splicing is frequent during early embryonic development in mouse.

    Revil T, Gaffney D, Dias C, Majewski J and Jerome-Majewska LA

    BMC genomics 2010;11;399

  • Effect of the assignment of ancestral CpG state on the estimation of nucleotide substitution rates in mammals.

    Gaffney DJ and Keightley PD

    BMC evolutionary biology 2008;8;265

  • Selective constraints in experimentally defined primate regulatory regions.

    Gaffney DJ, Blekhman R and Majewski J

    PLoS genetics 2008;4;8;e1000157

  • The scale of mutational variation in the murid genome.

    Gaffney DJ and Keightley PD

    Genome research 2005;15;8;1086-94

  • Functional constraints and frequency of deleterious mutations in noncoding DNA of rodents.

    Keightley PD and Gaffney DJ

    Proceedings of the National Academy of Sciences of the United States of America 2003;100;23;13402-6