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
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164 results found

Sandelin A, Alkema W, Engström P, Wasserman WW, Lenhard Bet al., 2004, JASPAR: An open-access database for eukaryotic transcription factor binding profiles, Nucleic Acids Research, Vol: 32, ISSN: 0305-1048

The analysis of regulatory regions in genome sequences is strongly based on the detection of potential transcription factor binding sites. The preferred models for representation of transcription factor binding specificity have been termed position-specific scoring matrices. JASPAR is an open-access database of annotated, high-quality, matrix-based transcription factor binding site profiles for multicellular eukaryotes. The profiles were derived exclusively from sets of nucleotide sequences experimentally demonstrated to bind transcription factors. The database is complemented by a web interface for browsing, searching and subset selection, an online sequence analysis utility and a suite of programming tools for genomewide and comparative genomic analysis of regulatory regions. JASPAR is available at http://jaspar.cgb.ki.se.

Journal article

Fredman D, Munns G, Rios D, Sjoholm F, Siegfried M, Lenhard B, Lehvaslaiho H, Brookes AJet al., 2004, HGVbase: a curated resource describing human DNA variation and phenotype relationships, NUCLEIC ACIDS RESEARCH, Vol: 32, Pages: D516-D519, ISSN: 0305-1048

Journal article

Sandelin A, Höglund A, Lenhard B, Wasserman WWet al., 2003, Integrated analysis of yeast regulatory sequences for biologically linked clusters of genes., Funct Integr Genomics, Vol: 3, Pages: 125-134, ISSN: 1438-793X

Dramatic progress in deciphering the regulatory controls in Saccharomyces cerevisiae has been enabled by the fusion of high-throughput genomics technologies with advanced sequence analysis algorithms. Sets of genes likely to function together and with similar expression profiles have been identified in diverse studies. By fusing an advanced pattern recognition algorithm for identification of transcription factor binding sites with a new method for the quantitative comparison of binding properties of transcription factors, we provide an integrated means to move from expression data to biological insights. The Yeast Regulatory Sequence Analysis system, YRSA, combines standard functions with a novel pattern characterization procedure in an intuitive interface designed for use by a broad range of scientists. The features of the system include automated retrieval of user-defined promoter sequences, binding site discovery by pattern recognition, graphical displays of the observed pattern and positions of similar sequences in the specified genes, and comparison of the new pattern against a collection of binding patterns for characterized transcription factors. The comprehensive YRSA system was used to study the regulatory mechanisms of yeast regulons. Analysis of the regulatory controls of a battery of genes induced by DNA damaging agents supports a putative mediating role for the cell-cycle checkpoint regulatory element MCB. YRSA is available at http://yrsa.cgb.ki.se. [YRSA: ancient Scandinavian name meaning old she-bear (Latin Ursus arctos = brown bear/grizzly).]

Journal article

Lenhard B, Wahlestedt C, Wasserman WW, 2003, GeneLynx Mouse: Integrated portal to the mouse genome, GENOME RESEARCH, Vol: 13, Pages: 1501-1504, ISSN: 1088-9051

Journal article

Lenhard B, Sandelin A, Mendoza L, Engström P, Jareborg N, Wasserman WWet al., 2003, Identification of conserved regulatory elements by comparative genome analysis., J Biol, Vol: 2

BACKGROUND: For genes that have been successfully delineated within the human genome sequence, most regulatory sequences remain to be elucidated. The annotation and interpretation process requires additional data resources and significant improvements in computational methods for the detection of regulatory regions. One approach of growing popularity is based on the preferential conservation of functional sequences over the course of evolution by selective pressure, termed 'phylogenetic footprinting'. Mutations are more likely to be disruptive if they appear in functional sites, resulting in a measurable difference in evolution rates between functional and non-functional genomic segments. RESULTS: We have devised a flexible suite of methods for the identification and visualization of conserved transcription-factor-binding sites. The system reports those putative transcription-factor-binding sites that are both situated in conserved regions and located as pairs of sites in equivalent positions in alignments between two orthologous sequences. An underlying collection of metazoan transcription-factor-binding profiles was assembled to facilitate the study. This approach results in a significant improvement in the detection of transcription-factor-binding sites because of an increased signal-to-noise ratio, as demonstrated with two sets of promoter sequences. The method is implemented as a graphical web application, ConSite, which is at the disposal of the scientific community at http://www.phylofoot.org/. CONCLUSIONS: Phylogenetic footprinting dramatically improves the predictive selectivity of bioinformatic approaches to the analysis of promoter sequences. ConSite delivers unparalleled performance using a novel database of high-quality binding models for metazoan transcription factors. With a dynamic interface, this bioinformatics tool provides broad access to promoter analysis with phylogenetic footprinting.

Journal article

Okazaki Y, Furuno M, Kasukawa T, Adachi J, Bono H, Kondo S, Nikaido I, Osato N, Saito R, Suzuki H, Yamanaka I, Kiyosawa H, Yagi K, Tomaru Y, Hasegawa Y, Nogami A, Schonbach C, Gojobori T, Baldarelli R, Hill DP, Bult C, Hume DA, Quackenbush J, Schriml LM, Kanapin A, Matsuda H, Batalov S, Beisel KW, Blake JA, Bradt D, Brusic V, Chothia C, Corbani LE, Cousins S, Dalla E, Dragani TA, Fletcher CF, Forrest A, Frazer KS, Gaasterland T, Gariboldi M, Gissi C, Godzik A, Gough J, Grimmond S, Gustincich S, Hirokawa N, Jackson IJ, Jarvis ED, Kanai A, Kawaji H, Kawasawa Y, Kedzierski RM, King BL, Konagaya A, Kurochkin IV, Lee Y, Lenhard B, Lyons PA, Maglott DR, Maltais L, Marchionni L, McKenzie L, Miki H, Nagashima T, Numata K, Okido T, Pavan WJ, Pertea G, Pesole G, Petrovsky N, Pillai R, Pontius JU, Qi D, Ramachandran S, Ravasi T, Reed JC, Reed DJ, Reid J, Ring BZ, Ringwald M, Sandelin A, Schneider C, Semple CAM, Setou M, Shimada K, Sultana R, Takenaka Y, Taylor MS, Teasdale RD, Tomita M, Verardo R, Wagner L, Wahlestedt C, Wang Y, Watanabe Y, Wells C, Wilming LG, Wynshaw-Boris A, Yanagisawa M, Yang I, Yang L, Yuan Z, Zavolan M, Zhu Y, Zimmer A, Carninci P, Hayatsu N, Hirozane-Kishikawa T, Konno H, Nakamura M, Sakazume N, Sato K, Shiraki T, Waki K, Kawai J, Aizawa K, Arakawa T, Fukuda S, Hara A, Hashizume W, Imotani K, Ishii Y, Itoh M, Kagawa I, Miyazaki A, Sakai K, Sasaki D, Shibata K, Shinagawa A, Yasunishi A, Yoshino M, Waterston R, Lander ES, Rogers J, Birney E, Hayashizaki Yet al., 2002, Analysis of the mouse transcriptome based on functional annotation of 60,770 full-length cDNAs, NATURE, Vol: 420, Pages: 563-573, ISSN: 0028-0836

Journal article

Lenhard B, Wasserman WW, 2002, TFBS: Computational framework for transcription factor binding site analysis, BIOINFORMATICS, Vol: 18, Pages: 1135-1136, ISSN: 1367-4803

Journal article

Lenhard B, Hayes WS, Wasserman WW, 2001, GeneLynx: A gene-centric portal to the human genome, GENOME RESEARCH, Vol: 11, Pages: 2151-2157, ISSN: 1088-9051

Journal article

Mijakovic I, Lenhard B, Weygand-Durasevic I, 1999, Evolutionary relationships of seryl-tRNA synthetases based on 3D modeling, PERIODICUM BIOLOGORUM, Vol: 101, Pages: 319-324, ISSN: 0031-5362

Journal article

Lenhard B, Orellana O, Ibba M, Weygand-Durasevic Iet al., 1999, tRNA recognition and evolution of determinants in seryl-tRNA synthesis, NUCLEIC ACIDS RESEARCH, Vol: 27, Pages: 721-729, ISSN: 0305-1048

Journal article

Lenhard B, Praetorius-Ibba M, Filipic S, Soll D, Weygand-Durasevic Iet al., 1998, C-terminal truncation of yeast SerRS is toxic for Saccharomyces cerevisiae due to altered mechanism of substrate recognition, FEBS LETTERS, Vol: 439, Pages: 235-240, ISSN: 1873-3468

Journal article

Lenhard B, Filipic S, Landeka I, Skrtic I, Soll D, WeygandDurasevic Iet al., 1997, Defining the active site of yeast Seryl-tRNA synthetase - Mutations in motif 2 loop residues affect tRNA-dependent amino acid recognition, JOURNAL OF BIOLOGICAL CHEMISTRY, Vol: 272, Pages: 1136-1141, ISSN: 0021-9258

Journal article

WeygandDurasevic I, Lenhard D, Filipic S, Soll Det al., 1996, The C-terminal extension of yeast seryl-tRNA synthetase affects stability of the enzyme and its substrate affinity, JOURNAL OF BIOLOGICAL CHEMISTRY, Vol: 271, Pages: 2455-2461, ISSN: 0021-9258

Journal article

Yu C, Cvetesic N, Gupta K, Ye T, Gazdag E, Hisler V, Negroni L, Hajkova P, Lenhard B, Müller F, Berger I, Vincent SD, Tora Let al., TBPL2/TFIIA complex overhauls oocyte transcriptome during oocyte growth

<jats:p>The first steps of oocyte development from primordial follicle are characterised by a growth phase, when unique RNA and protein reserves are created to achieve oocyte competence. During this growth, oocytes do not divide and the general transcription factor TATA binding protein (TBP) is replaced by its paralogue, TBPL2 (also called TBP2 or TRF3), which is essential for RNA polymerase II transcription (Pol II) <jats:sup>1,2</jats:sup>. However, the composition and function of transcription machinery and the regulatory mechanisms mediating Pol II transcription during this developmental stage remain unknown. In somatic cells, the general transcription factor TFIID, which contains TBP and 13 TBP-associated factors, is the first to bind gene promoters to nucleate Pol II transcription initiation<jats:sup>3</jats:sup>. Here, we show that in oocytes TBPL2 does not assemble into a canonical TFIID complex, while it stably associates with TFIIA via distinct TFIIA interactions when compared to TBP. Our transcript analyses in wild type and <jats:italic>Tbpl2</jats:italic><jats:sup><jats:italic>-/-</jats:italic></jats:sup> oocytes demonstrates that TBPL2 mediates transcription of oocyte-expressed genes, including mRNA destabilisation factors genes, as well as specific endogenous retroviral elements (ERVs). Transcription start site (TSS) mapping from wild-type and <jats:italic>Tbpl2</jats:italic><jats:sup><jats:italic>-/-</jats:italic></jats:sup> growing oocytes demonstrates that TBPL2 has a strong preference for TATA-like motif in gene core promoters driving specific sharp TSS selection. This is in marked contrast with TBP/TFIID-driven TATA-less gene promoters in preceding stages that have broad TSS architecture. We anticipate that our findings describing oocyte-specific transcription regulation will help to understand the mechanisms associated with primary ovarian insuff

Journal article

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