Imperial College London

ProfessorBorisLenhard

Faculty of MedicineInstitute of Clinical Sciences

Professor of Computational Biology
 
 
 
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Contact

 

+44 (0)20 3313 8353b.lenhard Website

 
 
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Assistant

 

Mr Alastair Douglas Ivor Williams +44 (0)20 3313 4318

 
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Location

 

230ICTEM buildingHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

149 results found

Tan G, Polychronopoulos D, Lenhard B, 2019, CNEr: a toolkit for exploring extreme noncoding conservation

Abstract Conserved Noncoding Elements (CNEs) are elements exhibiting extreme noncoding conservation in Metazoan genomes. They cluster around developmental genes and act as long-range enhancers, yet nothing that we know about their function explains the observed conservation levels. Clusters of CNEs coincide with topologically associating domains (TADs), indicating ancient origins and stability of TAD locations. This has suggested further hypotheses about the still elusive origin of CNEs, and has provided a comparative genomics-based method of estimating the position of TADs around developmentally regulated genes in genomes where chromatin conformation capture data is missing. To enable researchers in gene regulation and chromatin biology to start deciphering this phenomenon, we developed CNEr , a R/Bioconductor toolkit for large-scale identification of CNEs and for studying their genomic properties. We apply CNEr to two novel genome comparisons - fruit fly vs tsetse fly, and two sea urchin genomes - and report novel insights gained from their analysis. We also show how to reveal interesting characteristics of CNEs by coupling CNEr with existing Bioconductor packages. CNEr is available at Bioconductor ( https://bioconductor.org/packages/CNEr/ ) and maintained at github ( https://github.com/ge11232002/CNEr ).

WORKING PAPER

Börlin CS, Cvetesic N, Holland P, Bergenholm D, Siewers V, Lenhard B, Nielsen Jet al., 2019, Saccharomyces cerevisiae displays a stable transcription start site landscape in multiple conditions., FEMS Yeast Res, Vol: 19

One of the fundamental processes that determine cellular fate is regulation of gene transcription. Understanding these regulatory processes is therefore essential for understanding cellular responses to changes in environmental conditions. At the core promoter, the regulatory region containing the transcription start site (TSS), all inputs regulating transcription are integrated. Here, we used Cap Analysis of Gene Expression (CAGE) to analyze the pattern of TSSs at four different environmental conditions (limited in ethanol, limited in nitrogen, limited in glucose and limited in glucose under anaerobic conditions) using the Saccharomyces cerevisiae strain CEN.PK113-7D. With this experimental setup, we were able to show that the TSS landscape in yeast is stable at different metabolic states of the cell. We also show that the spatial distribution of transcription initiation events, described by the shape index, has a surprisingly strong negative correlation with measured gene expression levels, meaning that genes with higher expression levels tend to have a broader distribution of TSSs. Our analysis supplies a set of high-quality TSS annotations useful for metabolic engineering and synthetic biology approaches in the industrially relevant laboratory strain CEN.PK113-7D, and provides novel insights into yeast TSS dynamics and gene regulation.

JOURNAL ARTICLE

Newton MD, Taylor BJ, Driessen RPC, Roos L, Cvetesic N, Allyjaun S, Lenhard B, Cuomo ME, Rueda DSet al., 2019, DNA stretching induces Cas9 off-target activity, NATURE STRUCTURAL & MOLECULAR BIOLOGY, Vol: 26, Pages: 185-+, ISSN: 1545-9993

JOURNAL ARTICLE

Nash AJ, Lenhard B, 2018, A Novel Measure of Non-coding Genome Conservation Identifies Genomic Regulatory Blocks Within Primates., Bioinformatics

Motivation: Clusters of extremely conserved non-coding elements (CNEs) mark genomic regions devoted to cis-regulation of key developmental genes in Metazoa. We have recently shown that their span coincides with that of topologically associating domains (TADs), making them useful for estimating conserved TAD boundaries in the absence of Hi-C data. The standard approach - detecting CNEs in genome alignments and then establishing the boundaries of their clusters - requires tuning of several parameters and breaks down when comparing closely related genomes. Results: We present a novel, kurtosis-based measure of pairwise non-coding conservation that requires no pre-set thresholds for conservation level and length of CNEs. We show that it performs robustly across a large span of evolutionary distances, including across the closely related genomes of primates for which standard approaches fail. The method is straightforward to implement and enables detection and comparison of clusters of CNEs and estimation of underlying TADs across a vastly increased range of Metazoan genomes. Supplementary information: Supplementary data are available at Bioinformatics online.

JOURNAL ARTICLE

Marletaz F, Firbas PN, Maeso I, Tena JJ, Bogdanovic O, Perry M, Wyatt CDR, de la Calle-Mustienes E, Bertrand S, Burguera D, Acemel RD, van Heeringen SJ, Naranjo S, Herrera-Ubeda C, Skvortsova K, Jimenez-Gancedo S, Aldea D, Marquez Y, Buono L, Kozmikova I, Permanyer J, Louis A, Albuixech-Crespo B, Le Petillon Y, Leon A, Subirana L, Balwierz PJ, Duckett PE, Farahani E, Aury J-M, Mangenot S, Wincker P, Albalat R, Benito-Gutierrez E, Canestro C, Castro F, D'Aniello S, Ferrier DEK, Huang S, Laudet V, Marais GAB, Pontarotti P, Schubert M, Seitz H, Somorjai I, Takahashi T, Mirabeau O, Xu A, Yu J-K, Carninci P, Ramon Martinez-Morales J, Crollius HR, Kozmik Z, Weirauch MT, Garcia-Fernandez J, Lister R, Lenhard B, Holland PWH, Escriva H, Luis Gomez-Skarmeta J, Irimia Met al., 2018, Amphioxus functional genomics and the origins of vertebrate gene regulation, NATURE, Vol: 564, Pages: 64-+, ISSN: 0028-0836

JOURNAL ARTICLE

Cvetesic N, Leitch HG, Borkowska M, Mueller F, Carninci P, Hajkova P, Lenhard Bet al., 2018, SLIC-CAGE: high-resolution transcription start site mapping using nanogram-levels of total RNA, GENOME RESEARCH, Vol: 28, Pages: 1943-1956, ISSN: 1088-9051

JOURNAL ARTICLE

Cuartero S, Weiss FD, Dharmalingam G, Guo Y, Ing-Simmons E, Masella S, Robles-Rebollo I, Xiao X, Wang Y-F, Barozzi I, Djeghloul D, Amano MT, Niskanen H, Petretto E, Dowell RD, Tachibana K, Kaikkonen MU, Nasmyth KA, Lenhard B, Natoli G, Fisher AG, Merkenschlager Met al., 2018, Control of inducible gene expression links cohesin to hematopoietic progenitor self-renewal and differentiation, NATURE IMMUNOLOGY, Vol: 19, Pages: 932-+, ISSN: 1529-2908

JOURNAL ARTICLE

Boerlin C, Cvetesic N, Holland P, Bergenholm D, Siewers V, Lenhard B, Nielsen Jet al., 2018, Saccharomyces cerevisiae displays a stable transcription start site landscape in multiple conditions

One of the fundamental processes that determine cellular fate is regulation of gene transcription. Understanding these regulatory processes is therefore essential for understanding cellular responses to changes in environmental conditions. At the core promoter, the regulatory region containing the transcription start site (TSS), all inputs regulating transcription are integrated. Here, we used Cap Analysis of Gene Expression (CAGE) to analyze the pattern of transcription start sites at four different environmental conditions (limited in ethanol, limited in nitrogen, limited in glucose and limited in glucose under anaerobic conditions) using the Saccharomyces cerevisiae strain CEN.PK113-7D. With this experimental setup we were able to show that the TSS landscape in yeast is stable at different metabolic states of the cell. We also show that the shape index, a characteristic feature of each TSS describing the spatial distribution of transcription initiation events, has a surprisingly strong negative correlation with the measured expression levels. Our analysis supplies a set of high quality TSS annotations useful for metabolic engineering and synthetic biology approaches in the industrially relevant laboratory strain CEN.PK113-7D, and provides novel insights into yeast TSS dynamics and gene regulation.

OTHER

Lessel D, Gehbauer C, Bramswig NC, Schluth-Bolard C, Venkataramanappa S, van Gassen KLI, Hempel M, Haack TB, Baresic A, Genetti CA, Funari MFA, Lessel I, Kuhlmann L, Simon R, Liu P, Denecke J, Kuechler A, de Kruijff I, Shoukier M, Lek M, Mullen T, Luedecke H-J, Lerario AM, Kobbe R, Krieger T, Demeer B, Lebrun M, Keren B, Nava C, Buratti J, Afenjar A, Shinawi M, Sacoto MJG, Gauthier J, Hamdan FF, Laberge A-M, Campeau PM, Louie RJ, Cathey SS, Prinz I, Jorge AAL, Terhal PA, Lenhard B, Wieczorek D, Strom TM, Agrawal PB, Britsch S, Tolosa E, Kubisch Cet al., 2018, BCL11B mutations in patients affected by a neurodevelopmental disorder with reduced type 2 innate lymphoid cells, BRAIN, Vol: 141, Pages: 2299-2311, ISSN: 0006-8950

JOURNAL ARTICLE

Li C, Lenhard B, Luscombe NM, 2018, Integrated analysis sheds light on evolutionary trajectories of young transcription start sites in the human genome, GENOME RESEARCH, Vol: 28, Pages: 676-688, ISSN: 1088-9051

JOURNAL ARTICLE

Hill PWS, Leitch HG, Requena CE, Sun Z, Amouroux R, Roman-Trufero M, Borkowska M, Terragni J, Vaisvila R, Linnett S, Bagci H, Dharmalingham G, Haberle V, Lenhard B, Zheng Y, Pradhan S, Hajkova Pet al., 2018, Epigenetic reprogramming enables the transition from primordial germ cell to gonocyte, NATURE, Vol: 555, Pages: 392-+, ISSN: 0028-0836

JOURNAL ARTICLE

Danks GB, Navratilova P, Lenhard B, Thompson EMet al., 2018, Distinct core promoter codes drive transcription initiation at key developmental transitions in a marine chordate, BMC GENOMICS, Vol: 19, ISSN: 1471-2164

JOURNAL ARTICLE

Khan A, Fornes O, Stigliani A, Gheorghe M, Castro-Mondragon JA, van der Lee R, Bessy A, Cheneby J, Kulkarni SR, Tan G, Baranasic D, Arenillas DJ, Sandelin A, Vandepoele K, Lenhard B, Ballester B, Wasserman WW, Parcy F, Mathelier Aet al., 2018, JASPAR 2018: update of the open-access database of transcription factor binding profiles and its web framework (vol 46, pg 260, 2017), Publisher: OXFORD UNIV PRESS

OTHER

Khan A, Fornes O, Stigliani A, Gheorghe M, Castro-Mondragon JA, van der Lee R, Bessy A, Cheneby J, Kulkarni SR, Tan G, Baranasic D, Arenillas DJ, Sandelin A, Vandepoele K, Lenhard B, Ballester B, Wasserman WW, Parcy F, Mathelier Aet al., 2018, JASPAR 2018: update of the open-access database of transcription factor binding profiles and its web framework, NUCLEIC ACIDS RESEARCH, Vol: 46, Pages: D260-D266, ISSN: 0305-1048

JOURNAL ARTICLE

Polychronopoulos D, King JWD, Nash AJ, Tan G, Lenhard Bet al., 2017, Conserved non-coding elements: developmental gene regulation meets genome organization, NUCLEIC ACIDS RESEARCH, Vol: 45, ISSN: 0305-1048

JOURNAL ARTICLE

Siriboonpiputtana T, Zeisig BB, Zarowiecki M, Fung TK, Mallardo M, Tsai C-T, Lau PNL, Quoc CH, Veiga P, Barnes J, Lynn C, Wilson A, Lenhard B, So CWEet al., 2017, Transcriptional memory of cells of origin overrides beta-catenin requirement of MLL cancer stem cells, EMBO JOURNAL, Vol: 36, Pages: 3139-3155, ISSN: 0261-4189

JOURNAL ARTICLE

Harmston N, Ing-Simmons E, Tan G, Perry M, Merkenschlager M, Lenhard Bet al., 2017, Topologically associating domains are ancient features that coincide with Metazoan clusters of extreme noncoding conservation, NATURE COMMUNICATIONS, Vol: 8, ISSN: 2041-1723

JOURNAL ARTICLE

Cvetesic N, Lenhard B, 2017, Core promoters across the genome, NATURE BIOTECHNOLOGY, Vol: 35, Pages: 123-124, ISSN: 1087-0156

JOURNAL ARTICLE

Cantone I, Dharmalingam G, Chan Y-W, Kohler A-C, Lenhard B, Merkenschlager M, Fisher AGet al., 2017, Allele-specific analysis of cell fusion-mediated pluripotent reprograming reveals distinct and predictive susceptibilities of human X-linked genes to reactivation, GENOME BIOLOGY, Vol: 18, ISSN: 1474-760X

JOURNAL ARTICLE

Adlakha A, Armstrong-James DAJ, Lenhard B, 2016, CALCINEURIN INHIBITION IMPAIRS THE DENDRITIC CELL TRANSCRIPTIONAL RESPONSE TO ASPERGILLUS FUMIGATUS INFECTION IN LUNG TRANSPLANT RECIPIENTS, THORAX, Vol: 71, Pages: A1-A1, ISSN: 0040-6376

JOURNAL ARTICLE

Kolder ICRM, van der Plas-Duivesteijn SJ, Tan G, Wiegertjes GF, Forlenza M, Guler AT, Travin DY, Nakao M, Moritomo T, Irnazarow I, den Dunnen JT, Anvar SY, Jansen HJ, Dirks RP, Palmblad M, Lenhard B, Henkel CV, Spaink HPet al., 2016, A full-body transcriptome and proteome resource for the European common carp, BMC GENOMICS, Vol: 17, ISSN: 1471-2164

JOURNAL ARTICLE

Haberle V, Lenhard B, 2016, Promoter architectures and developmental gene regulation, SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY, Vol: 57, Pages: 11-23, ISSN: 1084-9521

JOURNAL ARTICLE

Adlakha A, Armstrong-James DPH, Lenhard B, 2016, The role of calcineurin inhibition in the dendritic cell response to Aspergillus fumigatus infection in lung transplant recipients, Publisher: LIPPINCOTT WILLIAMS & WILKINS, Pages: S371-S371, ISSN: 0041-1337

CONFERENCE PAPER

Tan G, Lenhard B, 2016, TFBSTools: an R/bioconductor package for transcription factor binding site analysis, BIOINFORMATICS, Vol: 32, Pages: 1555-1556, ISSN: 1367-4803

JOURNAL ARTICLE

Nepal C, Coolen M, Hadzhiev Y, Cussigh D, Mydel P, Steen VM, Carninci P, Andersen JB, Bally-Cuif L, Muller F, Lenhard Bet al., 2016, Transcriptional, post-transcriptional and chromatin-associated regulation of pri-miRNAs, pre-miRNAs and moRNAs, NUCLEIC ACIDS RESEARCH, Vol: 44, Pages: 3070-3081, ISSN: 0305-1048

JOURNAL ARTICLE

Cvetesic N, Dulic M, Bilus M, Sostaric N, Lenhard B, Gruic-Sovulj Iet al., 2016, Naturally Occurring Isoleucyl-tRNA Synthetase without tRNA-dependent Pre-transfer Editing, JOURNAL OF BIOLOGICAL CHEMISTRY, Vol: 291, Pages: 8618-8631, ISSN: 0021-9258

JOURNAL ARTICLE

Adlakha A, Armstrong-James D, Lenhard B, 2016, Effect of calcineurin inhibition on phenotypic maturation of dendritic cells in an in-vitro model of invasive aspergillosis in lung transplant recipients, Spring Meeting on Clinician Scientists in Training, Publisher: ELSEVIER SCIENCE INC, Pages: 16-16, ISSN: 0140-6736

CONFERENCE PAPER

Cheung N, Fung TK, Zeisig BB, Holmes K, Rane JK, Mowen KA, Finn MG, Lenhard B, Chan LC, So CWEet al., 2016, Targeting Aberrant Epigenetic Networks Mediated by PRMT1 and KDM4C in Acute Myeloid Leukemia, CANCER CELL, Vol: 29, Pages: 32-48, ISSN: 1535-6108

JOURNAL ARTICLE

Mathelier A, Fornes O, Arenillas DJ, Chen C-Y, Denay G, Lee J, Shi W, Shyr C, Tan G, Worsley-Hunt R, Zhang AW, Parcy F, Lenhard B, Sandelin A, Wasserman WWet al., 2016, JASPAR 2016: a major expansion and update of the open-access database of transcription factor binding profiles, NUCLEIC ACIDS RESEARCH, Vol: 44, Pages: D110-D115, ISSN: 0305-1048

JOURNAL ARTICLE

Adlakha AG, Armstrong-James DPH, Lenhard B, 2015, CALCINEURIN INHIBITION IMPAIRS PHENOTYPIC MATURATION OF DENDRITIC CELLS IN A IN VITRO MODEL OF INVASIVE ASPERGILLOSIS IN LUNG TRANSPLANT RECIPIENTS, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A48-A49, ISSN: 0040-6376

CONFERENCE PAPER

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