Viktor Gal, PhD. Computer Science
Everything not saved will be lost
Abstract Transcription factor (TF) DNA sequence preferences direct their regulatory activity, but are currently known for only ∼1% of eukaryotic TFs. Broadly sampling DNA-binding domain (DBD) types from multiple eukaryotic clades, we determined DNA sequence preferences for >1,000 TFs encompassing 54 different DBD classes from 131 diverse eukaryotes. We find that closely related DBDs almost always have very similar DNA sequence preferences, enabling inference of motifs for ∼34% of the ∼170,000 known or predicted eukaryotic TFs. Sequences matching both measured and inferred motifs are enriched in chromatin immunoprecipitation sequencing (ChIP-seq) peaks and upstream of transcription start sites in diverse eukaryotic lineages. SNPs defining expression quantitative trait loci in Arabidopsis promoters are also enriched for predicted TF binding sites. Importantly, our motif "library" can be used to identify specific TFs whose binding may be altered by human disease risk alleles. These data present a powerful resource for mapping transcriptional networks across eukaryotes.
Authors Matthew T Weirauch, Ally Yang, Mihai Albu, Atina G Cote, Alejandro Montenegro Montero, Philipp Drewe, Hamed S Najafabadi, Samuel A Lambert, Ishminder Mann, Kate Cook, Hong Zheng, Alejandra Goity, Harm van Bakel, Jean Claude Lozano, Mary Galli, Mathew G Lewsey, Eryong Huang, Tuhin Mukherjee, Xiaoting Chen, John S Reece Hoyes, Sridhar Govindarajan, Gad Shaulsky, Albertha J M Walhout, Francois Yves Bouget, Gunnar Rätsch, Luis F Larrondo, Joseph R Ecker, Timothy R Hughes
Abstract We systematically generated large-scale data sets to improve genome annotation for the nematode Caenorhabditis elegans, a key model organism. These data sets include transcriptome profiling across a developmental time course, genome-wide identification of transcription factor-binding sites, and maps of chromatin organization. From this, we created more complete and accurate gene models, including alternative splice forms and candidate noncoding RNAs. We constructed hierarchical networks of transcription factor-binding and microRNA interactions and discovered chromosomal locations bound by an unusually large number of transcription factors. Different patterns of chromatin composition and histone modification were revealed between chromosome arms and centers, with similarly prominent differences between autosomes and the X chromosome. Integrating data types, we built statistical models relating chromatin, transcription factor binding, and gene expression. Overall, our analyses ascribed putative functions to most of the conserved genome.
Authors Mark B Gerstein, Zhi John Lu, Eric L Van Nostrand, Chao Cheng, Bradley I Arshinoff, Tao Liu, Kevin Y Yip, Rebecca Robilotto, Andreas Rechtsteiner, Kohta Ikegami, Pedro Alves, Aurelien Chateigner, Marc Perry, Mitzi Morris, Raymond K Auerbach, Xin Feng, Jing Leng, Anne Vielle, Wei Niu, Kahn Rhrissorrakrai, Ashish Agarwal, Roger P Alexander, Galt Barber, Cathleen M Brdlik, Jennifer Brennan, Jeremy Jean Brouillet, Adrian Carr, Ming Sin Cheung, Hiram Clawson, Sergio Contrino, Luke O Dannenberg, Abby F Dernburg, Arshad Desai, Lindsay Dick, Andrea C Dose, Jiang Du, Thea Egelhofer, Sevinc Ercan, Ghia Euskirchen, Brent Ewing, Elise A Feingold, Reto Gassmann, Peter J Good, Phil Green, Francois Gullier, Michelle Gutwein, Mark S Guyer, Lukas Habegger, Ting Han, Jorja G Henikoff, Stefan R Henz, Angie Hinrichs, Heather Holster, Tony Hyman, A Leo Iniguez, Judith Janette, Morten Jensen, Masaomi Kato, W James Kent, Ellen Kephart, Vishal Khivansara, Ekta Khurana, John K Kim, Paulina Kolasinska Zwierz, Eric C Lai, Isabel Latorre, Amber Leahey, Suzanna Lewis, Paul Lloyd, Lucas Lochovsky, Rebecca F Lowdon, Yaniv Lubling, Rachel Lyne, Michael MacCoss, Sebastian D Mackowiak, Marco Mangone, Sheldon McKay, Desirea Mecenas, Gennifer Merrihew, David M Miller, Andrew Muroyama, John I Murray, Siew Loon Ooi, Hoang Pham, Taryn Phippen, Elicia A Preston, Nikolaus Rajewsky, Gunnar Rätsch, Heidi Rosenbaum, Joel Rozowsky, Kim Rutherford, Peter Ruzanov, Mihail Sarov, Rajkumar Sasidharan, Andrea Sboner, Paul Scheid, Eran Segal, Hyunjin Shin, Chong Shou, Frank J Slack, Cindie Slightam, Richard Smith, William C Spencer, E O Stinson, Scott Taing, Teruaki Takasaki, Dionne Vafeados, Ksenia Voronina, Guilin Wang, Nicole L Washington, Christina M Whittle, Beijing Wu, Koon Kiu Yan, Georg Zeller, Zheng Zha, Mei Zhong, Xingliang Zhou, Julie Ahringer, Susan Strome, Kristin C Gunsalus, Gos Micklem, X Shirley Liu, Valerie Reinke, Sang Tae Kim, LaDeana W Hillier, Steven Henikoff, Fabio Piano, Michael Snyder, Lincoln Stein, Jason D Lieb, Robert H Waterston
Submitted Science (New York, N.Y.)
Abstract Since prilocaine is being increasingly used for day case surgery as a short acting local anaesthetic for spinal anaesthesia and because of its low risk for transient neurological symptoms, we compared it to bupivacaine.
Authors Gunnar Rätsch, H Niebergall, L Hauenstein, A Reber
Submitted Der Anaesthesist