TY  - JOUR
A1  - Jiang, Yuxiang
A1  - Oron, Tal Ronnen
A1  - Clark, Wyatt T.
A1  - Bankapur, Asma R.
A1  - D'Andrea, Daniel
A1  - Lepore, Rosalba
A1  - Funk, Christopher S.
A1  - Kahanda, Indika
A1  - Verspoor, Karin M.
A1  - Ben-Hur, Asa
A1  - Koo, Da Chen Emily
A1  - Penfold-Brown, Duncan
A1  - Shasha, Dennis
A1  - Youngs, Noah
A1  - Bonneau, Richard
A1  - Lin, Alexandra
A1  - Sahraeian, Sayed M. E.
A1  - Martelli, Pier Luigi
A1  - Profiti, Giuseppe
A1  - Casadio, Rita
A1  - Cao, Renzhi
A1  - Zhong, Zhaolong
A1  - Cheng, Jianlin
A1  - Altenhoff, Adrian
A1  - Skunca, Nives
A1  - Dessimoz, Christophe
A1  - Dogan, Tunca
A1  - Hakala, Kai
A1  - Kaewphan, Suwisa
A1  - Mehryary, Farrokh
A1  - Salakoski, Tapio
A1  - Ginter, Filip
A1  - Fang, Hai
A1  - Smithers, Ben
A1  - Oates, Matt
A1  - Gough, Julian
A1  - Törönen, Petri
A1  - Koskinen, Patrik
A1  - Holm, Liisa
A1  - Chen, Ching-Tai
A1  - Hsu, Wen-Lian
A1  - Bryson, Kevin
A1  - Cozzetto, Domenico
A1  - Minneci, Federico
A1  - Jones, David T.
A1  - Chapman, Samuel
A1  - BKC, Dukka
A1  - Khan, Ishita K.
A1  - Kihara, Daisuke
A1  - Ofer, Dan
A1  - Rappoport, Nadav
A1  - Stern, Amos
A1  - Cibrian-Uhalte, Elena
A1  - Denny, Paul
A1  - Foulger, Rebecca E.
A1  - Hieta, Reija
A1  - Legge, Duncan
A1  - Lovering, Ruth C.
A1  - Magrane, Michele
A1  - Melidoni, Anna N.
A1  - Mutowo-Meullenet, Prudence
A1  - Pichler, Klemens
A1  - Shypitsyna, Aleksandra
A1  - Li, Biao
A1  - Zakeri, Pooya
A1  - ElShal, Sarah
A1  - Tranchevent, Léon-Charles
A1  - Das, Sayoni
A1  - Dawson, Natalie L.
A1  - Lee, David
A1  - Lees, Jonathan G.
A1  - Sillitoe, Ian
A1  - Bhat, Prajwal
A1  - Nepusz, Tamás
A1  - Romero, Alfonso E.
A1  - Sasidharan, Rajkumar
A1  - Yang, Haixuan
A1  - Paccanaro, Alberto
A1  - Gillis, Jesse
A1  - Sedeño-Cortés, Adriana E.
A1  - Pavlidis, Paul
A1  - Feng, Shou
A1  - Cejuela, Juan M.
A1  - Goldberg, Tatyana
A1  - Hamp, Tobias
A1  - Richter, Lothar
A1  - Salamov, Asaf
A1  - Gabaldon, Toni
A1  - Marcet-Houben, Marina
A1  - Supek, Fran
A1  - Gong, Qingtian
A1  - Ning, Wei
A1  - Zhou, Yuanpeng
A1  - Tian, Weidong
A1  - Falda, Marco
A1  - Fontana, Paolo
A1  - Lavezzo, Enrico
A1  - Toppo, Stefano
A1  - Ferrari, Carlo
A1  - Giollo, Manuel
A1  - Piovesan, Damiano
A1  - Tosatto, Silvio C. E.
A1  - del Pozo, Angela
A1  - Fernández, José M.
A1  - Maietta, Paolo
A1  - Valencia, Alfonso
A1  - Tress, Michael L.
A1  - Benso, Alfredo
A1  - Di Carlo, Stefano
A1  - Politano, Gianfranco
A1  - Savino, Alessandro
A1  - Rehman, Hafeez Ur
A1  - Re, Matteo
A1  - Mesiti, Marco
A1  - Valentini, Giorgio
A1  - Bargsten, Joachim W.
A1  - van Dijk, Aalt D. J.
A1  - Gemovic, Branislava
A1  - Glisic, Sanja
A1  - Perovic, Vladmir
A1  - Veljkovic, Veljko
A1  - Almeida-e-Silva, Danillo C.
A1  - Vencio, Ricardo Z. N.
A1  - Sharan, Malvika
A1  - Vogel, Jörg
A1  - Kansakar, Lakesh
A1  - Zhang, Shanshan
A1  - Vucetic, Slobodan
A1  - Wang, Zheng
A1  - Sternberg, Michael J. E.
A1  - Wass, Mark N.
A1  - Huntley, Rachael P.
A1  - Martin, Maria J.
A1  - O'Donovan, Claire
A1  - Robinson, Peter N.
A1  - Moreau, Yves
A1  - Tramontano, Anna
A1  - Babbitt, Patricia C.
A1  - Brenner, Steven E.
A1  - Linial, Michal
A1  - Orengo, Christine A.
A1  - Rost, Burkhard
A1  - Greene, Casey S.
A1  - Mooney, Sean D.
A1  - Friedberg, Iddo
A1  - Radivojac, Predrag
A1  - Veljkovic, Nevena
T1  - An expanded evaluation of protein function prediction methods shows an improvement in accuracy
JF  - Genome Biology
N2  - Background
A major bottleneck in our understanding of the molecular underpinnings of life is the assignment of function to proteins. While molecular experiments provide the most reliable annotation of proteins, their relatively low throughput and restricted purview have led to an increasing role for computational function prediction. However, assessing methods for protein function prediction and tracking progress in the field remain challenging.

Results
We conducted the second critical assessment of functional annotation (CAFA), a timed challenge to assess computational methods that automatically assign protein function. We evaluated 126 methods from 56 research groups for their ability to predict biological functions using Gene Ontology and gene-disease associations using Human Phenotype Ontology on a set of 3681 proteins from 18 species. CAFA2 featured expanded analysis compared with CAFA1, with regards to data set size, variety, and assessment metrics. To review progress in the field, the analysis compared the best methods from CAFA1 to those of CAFA2.

Conclusions
The top-performing methods in CAFA2 outperformed those from CAFA1. This increased accuracy can be attributed to a combination of the growing number of experimental annotations and improved methods for function prediction. The assessment also revealed that the definition of top-performing algorithms is ontology specific, that different performance metrics can be used to probe the nature of accurate predictions, and the relative diversity of predictions in the biological process and human phenotype ontologies. While there was methodological improvement between CAFA1 and CAFA2, the interpretation of results and usefulness of individual methods remain context-dependent.
KW  - Protein function prediction
KW  - Disease gene prioritization
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166293
VL  - 17
IS  - 184
ER  - 
TY  - JOUR
A1  - Ferreira, Manuel A.
A1  - Gamazon, Eric R.
A1  - Al-Ejeh, Fares
A1  - Aittomäki, Kristiina
A1  - Andrulis, Irene L.
A1  - Anton-Culver, Hoda
A1  - Arason, Adalgeir
A1  - Arndt, Volker
A1  - Aronson, Kristan J.
A1  - Arun, Banu K.
A1  - Asseryanis, Ella
A1  - Azzollini, Jacopo
A1  - Balmaña, Judith
A1  - Barnes, Daniel R.
A1  - Barrowdale, Daniel
A1  - Beckmann, Matthias W.
A1  - Behrens, Sabine
A1  - Benitez, Javier
A1  - Bermisheva, Marina
A1  - Bialkowska, Katarzyna
A1  - Blomqvist, Carl
A1  - Bogdanova, Natalia V.
A1  - Bojesen, Stig E.
A1  - Bolla, Manjeet K.
A1  - Borg, Ake
A1  - Brauch, Hiltrud
A1  - Brenner, Hermann
A1  - Broeks, Annegien
A1  - Burwinkel, Barbara
A1  - Caldés, Trinidad
A1  - Caligo, Maria A.
A1  - Campa, Daniele
A1  - Campbell, Ian
A1  - Canzian, Federico
A1  - Carter, Jonathan
A1  - Carter, Brian D.
A1  - Castelao, Jose E.
A1  - Chang-Claude, Jenny
A1  - Chanock, Stephen J.
A1  - Christiansen, Hans
A1  - Chung, Wendy K.
A1  - Claes, Kathleen B. M.
A1  - Clarke, Christine L.
A1  - Couch, Fergus J.
A1  - Cox, Angela
A1  - Cross, Simon S.
A1  - Czene, Kamila
A1  - Daly, Mary B.
A1  - de la Hoya, Miguel
A1  - Dennis, Joe
A1  - Devilee, Peter
A1  - Diez, Orland
A1  - Dörk, Thilo
A1  - Dunning, Alison M.
A1  - Dwek, Miriam
A1  - Eccles, Diana M.
A1  - Ejlertsen, Bent
A1  - Ellberg, Carolina
A1  - Engel, Christoph
A1  - Eriksson, Mikael
A1  - Fasching, Peter A.
A1  - Fletcher, Olivia
A1  - Flyger, Henrik
A1  - Friedman, Eitan
A1  - Frost, Debra
A1  - Gabrielson, Marike
A1  - Gago-Dominguez, Manuela
A1  - Ganz, Patricia A.
A1  - Gapstur, Susan M.
A1  - Garber, Judy
A1  - García-Closas, Montserrat
A1  - García-Sáenz, José A.
A1  - Gaudet, Mia M.
A1  - Giles, Graham G.
A1  - Glendon, Gord
A1  - Godwin, Andrew K.
A1  - Goldberg, Mark S.
A1  - Goldgar, David E.
A1  - González-Neira, Anna
A1  - Greene, Mark H.
A1  - Gronwald, Jacek
A1  - Guenél, Pascal
A1  - Haimann, Christopher A.
A1  - Hall, Per
A1  - Hamann, Ute
A1  - He, Wei
A1  - Heyworth, Jane
A1  - Hogervorst, Frans B. L.
A1  - Hollestelle, Antoinette
A1  - Hoover, Robert N.
A1  - Hopper, John L.
A1  - Hulick, Peter J.
A1  - Humphreys, Keith
A1  - Imyanitov, Evgeny N.
A1  - Isaacs, Claudine
A1  - Jakimovska, Milena
A1  - Jakubowska, Anna
A1  - James, Paul A.
A1  - Janavicius, Ramunas
A1  - Jankowitz, Rachel C.
A1  - John, Esther M.
A1  - Johnson, Nichola
A1  - Joseph, Vijai
A1  - Karlan, Beth Y.
A1  - Khusnutdinova, Elza
A1  - Kiiski, Johanna I.
A1  - Ko, Yon-Dschun
A1  - Jones, Michael E.
A1  - Konstantopoulou, Irene
A1  - Kristensen, Vessela N.
A1  - Laitman, Yael
A1  - Lambrechts, Diether
A1  - Lazaro, Conxi
A1  - Leslie, Goska
A1  - Lester, Jenny
A1  - Lesueur, Fabienne
A1  - Lindström, Sara
A1  - Long, Jirong
A1  - Loud, Jennifer T.
A1  - Lubiński, Jan
A1  - Makalic, Enes
A1  - Mannermaa, Arto
A1  - Manoochehri, Mehdi
A1  - Margolin, Sara
A1  - Maurer, Tabea
A1  - Mavroudis, Dimitrios
A1  - McGuffog, Lesley
A1  - Meindl, Alfons
A1  - Menon, Usha
A1  - Michailidou, Kyriaki
A1  - Miller, Austin
A1  - Montagna, Marco
A1  - Moreno, Fernando
A1  - Moserle, Lidia
A1  - Mulligan, Anna Marie
A1  - Nathanson, Katherine L.
A1  - Neuhausen, Susan L.
A1  - Nevanlinna, Heli
A1  - Nevelsteen, Ines
A1  - Nielsen, Finn C.
A1  - Nikitina-Zake, Liene
A1  - Nussbaum, Robert L.
A1  - Offit, Kenneth
A1  - Olah, Edith
A1  - Olopade, Olufunmilayo I.
A1  - Olsson, Håkan
A1  - Osorio, Ana
A1  - Papp, Janos
A1  - Park-Simon, Tjoung-Won
A1  - Parsons, Michael T.
A1  - Pedersen, Inge Sokilde
A1  - Peixoto, Ana
A1  - Peterlongo, Paolo
A1  - Pharaoh, Paul D. P.
A1  - Plaseska-Karanfilska, Dijana
A1  - Poppe, Bruce
A1  - Presneau, Nadege
A1  - Radice, Paolo
A1  - Rantala, Johanna
A1  - Rennert, Gad
A1  - Risch, Harvey A.
A1  - Saloustros, Emmanouil
A1  - Sanden, Kristin
A1  - Sawyer, Elinor J.
A1  - Schmidt, Marjanka K.
A1  - Schmutzler, Rita K.
A1  - Sharma, Priyanka
A1  - Shu, Xiao-Ou
A1  - Simard, Jaques
A1  - Singer, Christian F.
A1  - Soucy, Penny
A1  - Southey, Melissa C.
A1  - Spinelli, John J.
A1  - Spurdle, Amanda B.
A1  - Stone, Jennifer
A1  - Swerdlow, Anthony J.
A1  - Tapper, William J.
A1  - Taylor, Jack A.
A1  - Teixeira, Manuel R.
A1  - Terry, Mary Beth
A1  - Teulé, Alex
A1  - Thomassen, Mads
A1  - Thöne, Kathrin
A1  - Thull, Darcy L.
A1  - Tischkowitz, Marc
A1  - Toland, Amanda E.
A1  - Torres, Diana
A1  - Truong, Thérèse
A1  - Tung, Nadine
A1  - Vachon, Celine M.
A1  - van Asperen, Christi J.
A1  - van den Ouweland, Ans M. W.
A1  - van Rensburg, Elizabeth J.
A1  - Vega, Ana
A1  - Viel, Alexandra
A1  - Wang, Qin
A1  - Wappenschmidt, Barbara
A1  - Weitzel, Jeffrey N.
A1  - Wendt, Camilla
A1  - Winqvist, Robert
A1  - Yang, Xiaohong R.
A1  - Yannoukakos, Drakoulis
A1  - Ziogas, Argyrios
A1  - Kraft, Peter
A1  - Antoniou, Antonis C.
A1  - Zheng, Wei
A1  - Easton, Douglas F.
A1  - Milne, Roger L.
A1  - Beesley, Jonathan
A1  - Chenevix-Trench, Georgia
T1  - Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer
JF  - Nature Communications
N2  - Genome-wide association studies (GWAS) have identified more than 170 breast cancer susceptibility loci. Here we hypothesize that some risk-associated variants might act in non-breast tissues, specifically adipose tissue and immune cells from blood and spleen. Using expression quantitative trait loci (eQTL) reported in these tissues, we identify 26 previously unreported, likely target genes of overall breast cancer risk variants, and 17 for estrogen receptor (ER)-negative breast cancer, several with a known immune function. We determine the directional effect of gene expression on disease risk measured based on single and multiple eQTL. In addition, using a gene-based test of association that considers eQTL from multiple tissues, we identify seven (and four) regions with variants associated with overall (and ER-negative) breast cancer risk, which were not reported in previous GWAS. Further investigation of the function of the implicated genes in breast and immune cells may provide insights into the etiology of breast cancer.
KW  - cancer
KW  - genetics
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-228024
VL  - 10
ER  - 
TY  - JOUR
A1  - Benoit, Joshua B.
A1  - Adelman, Zach N.
A1  - Reinhardt, Klaus
A1  - Dolan, Amanda
A1  - Poelchau, Monica
A1  - Jennings, Emily C.
A1  - Szuter, Elise M.
A1  - Hagan, Richard W.
A1  - Gujar, Hemant
A1  - Shukla, Jayendra Nath
A1  - Zhu, Fang
A1  - Mohan, M.
A1  - Nelson, David R.
A1  - Rosendale, Andrew J.
A1  - Derst, Christian
A1  - Resnik, Valentina
A1  - Wernig, Sebastian
A1  - Menegazzi, Pamela
A1  - Wegener, Christian
A1  - Peschel, Nicolai
A1  - Hendershot, Jacob M.
A1  - Blenau, Wolfgang
A1  - Predel, Reinhard
A1  - Johnston, Paul R.
A1  - Ioannidis, Panagiotis
A1  - Waterhouse, Robert M.
A1  - Nauen, Ralf
A1  - Schorn, Corinna
A1  - Ott, Mark-Christoph
A1  - Maiwald, Frank
A1  - Johnston, J. Spencer
A1  - Gondhalekar, Ameya D.
A1  - Scharf, Michael E.
A1  - Raje, Kapil R.
A1  - Hottel, Benjamin A.
A1  - Armisén, David
A1  - Crumière, Antonin Jean Johan
A1  - Refki, Peter Nagui
A1  - Santos, Maria Emilia
A1  - Sghaier, Essia
A1  - Viala, Sèverine
A1  - Khila, Abderrahman
A1  - Ahn, Seung-Joon
A1  - Childers, Christopher
A1  - Lee, Chien-Yueh
A1  - Lin, Han
A1  - Hughes, Daniel S.T.
A1  - Duncan, Elizabeth J.
A1  - Murali, Shwetha C.
A1  - Qu, Jiaxin
A1  - Dugan, Shannon
A1  - Lee, Sandra L.
A1  - Chao, Hsu
A1  - Dinh, Huyen
A1  - Han, Yi
A1  - Doddapaneni, Harshavardhan
A1  - Worley, Kim C.
A1  - Muzny, Donna M.
A1  - Wheeler, David
A1  - Panfilio, Kristen A.
A1  - Jentzsch, Iris M. Vargas
A1  - Jentzsch, IMV
A1  - Vargo, Edward L.
A1  - Booth, Warren
A1  - Friedrich, Markus
A1  - Weirauch, Matthew T.
A1  - Anderson, Michelle A.E.
A1  - Jones, Jeffery W.
A1  - Mittapalli, Omprakash
A1  - Zhao, Chaoyang
A1  - Zhou, Jing-Jiang
A1  - Evans, Jay D.
A1  - Attardo, Geoffrey M.
A1  - Robertson, Hugh M.
A1  - Zdobnov, Evgeny M.
A1  - Ribeiro, Jose M.C.
A1  - Gibbs, Richard A.
A1  - Werren, John H.
A1  - Palli, Subba R.
A1  - Schal, Coby
A1  - Richards, Stephen
T1  - Unique features of a global human ectoparasite identified through sequencing of the bed bug genome
JF  - Nature Communications
N2  - The bed bug, Cimex lectularius, has re-established itself as a ubiquitous human ectoparasite throughout much of the world during the past two decades. This global resurgence is likely linked to increased international travel and commerce in addition to widespread insecticide resistance. Analyses of the C. lectularius sequenced genome (650 Mb) and 14,220 predicted protein-coding genes provide a comprehensive representation of genes that are linked to traumatic insemination, a reduced chemosensory repertoire of genes related to obligate hematophagy, host–symbiont interactions, and several mechanisms of insecticide resistance. In addition, we document the presence of multiple putative lateral gene transfer events. Genome sequencing and annotation establish a solid foundation for future research on mechanisms of insecticide resistance, human–bed bug and symbiont–bed bug associations, and unique features of bed bug biology that contribute to the unprecedented success of C. lectularius as a human ectoparasite.
KW  - human ectoparasite
KW  - bed bug
KW  - Cimex lectularius
KW  - genome
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166221
VL  - 7
IS  - 10165
ER  - 
TY  - JOUR
A1  - Higgins, M. J.
A1  - Smilinich, N. J.
A1  - Sait, S.
A1  - Koenig, A.
A1  - Pongratz, J.
A1  - Gessler, Manfred
A1  - Richard III., C. W.
A1  - James, M. R.
A1  - Sanford, J. P.
A1  - Kim, B.-W.
A1  - Cattelane, J.
A1  - Nowak, N. J.
A1  - Winterpacht, A.
A1  - Zabel, B. U.
A1  - Munroe, D. J.
A1  - Bric, E.
A1  - Housman, D. E.
A1  - Jones, C.
A1  - Nakamura, Y.
A1  - Gerhard, D. S.
A1  - Shows, T. B.
T1  - An Ordered NotI Fragment Map of Human Chromosome Band 11p15
N2  - An ordered NotI fragment map containing over 60 loci and encompassing approximately 17 Mb has been constructed for human chromosome band llpl5. Forty-two probes, including 11 NotI-linking cosmids, were subregionaUy mapped to llpl5 using a subset of the Jl-deletion hybrids. These and 23 other probes defining loci previously mapped to 11p15 were hybridized to genomic DNA digested with NotI and 5 other infrequently cleaving restriction enzymes and separated by pulsed-field gel electrophoresis. Thirty-nine distinct NotI fragments were detected encompassing approximately 85% of the estimated length of llp15. The predicted order of the gene loci used is cenMYODI- PTH-CALCA-ST5-RBTNI-HPX-HBB-RRMlTH/ INS!1GF2-H19-CTSD-MUC2-DRD4-HRAS-RNHtel. This map wiu allow higher resolution mapping of new Ilp15 markers, facilitate positional cloning of disease genes, and provide a framework for the physical mapping of llp15 in clone contigs.
KW  - Genom / Genkartierung / Genanalyse
Y1  - 1994
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-45766
ER  - 
TY  - JOUR
A1  - Gröbner, Susanne N.
A1  - Worst, Barbara C.
A1  - Weischenfeldt, Joachim
A1  - Buchhalter, Ivo
A1  - Kleinheinz, Kortine
A1  - Rudneva, Vasilisa A.
A1  - Johann, Pascal D.
A1  - Balasubramanian, Gnana Prakash
A1  - Segura-Wang, Maia
A1  - Brabetz, Sebastian
A1  - Bender, Sebastian
A1  - Hutter, Barbara
A1  - Sturm, Dominik
A1  - Pfaff, Elke
A1  - Hübschmann, Daniel
A1  - Zipprich, Gideon
A1  - Heinold, Michael
A1  - Eils, Jürgen
A1  - Lawerenz, Christian
A1  - Erkek, Serap
A1  - Lambo, Sander
A1  - Waszak, Sebastian
A1  - Blattmann, Claudia
A1  - Borkhardt, Arndt
A1  - Kuhlen, Michaela
A1  - Eggert, Angelika
A1  - Fulda, Simone
A1  - Gessler, Manfred
A1  - Wegert, Jenny
A1  - Kappler, Roland
A1  - Baumhoer, Daniel
A1  - Stefan, Burdach
A1  - Kirschner-Schwabe, Renate
A1  - Kontny, Udo
A1  - Kulozik, Andreas E.
A1  - Lohmann, Dietmar
A1  - Hettmer, Simone
A1  - Eckert, Cornelia
A1  - Bielack, Stefan
A1  - Nathrath, Michaela
A1  - Niemeyer, Charlotte
A1  - Richter, Günther H.
A1  - Schulte, Johannes
A1  - Siebert, Reiner
A1  - Westermann, Frank
A1  - Molenaar, Jan J.
A1  - Vassal, Gilles
A1  - Witt, Hendrik
A1  - Burkhardt, Birgit
A1  - Kratz, Christian P.
A1  - Witt, Olaf
A1  - van Tilburg, Cornelis M.
A1  - Kramm, Christof M.
A1  - Fleischhack, Gudrun
A1  - Dirksen, Uta
A1  - Rutkowski, Stefan
A1  - Frühwald, Michael
A1  - Hoff, Katja von
A1  - Wolf, Stephan
A1  - Klingebeil, Thomas
A1  - Koscielniak, Ewa
A1  - Landgraf, Pablo
A1  - Koster, Jan
A1  - Resnick, Adam C.
A1  - Zhang, Jinghui
A1  - Liu, Yanling
A1  - Zhou, Xin
A1  - Waanders, Angela J.
A1  - Zwijnenburg, Danny A.
A1  - Raman, Pichai
A1  - Brors, Benedikt
A1  - Weber, Ursula D.
A1  - Northcott, Paul A.
A1  - Pajtler, Kristian W.
A1  - Kool, Marcel
A1  - Piro, Rosario M.
A1  - Korbel, Jan O.
A1  - Schlesner, Matthias
A1  - Eils, Roland
A1  - Jones, David T. W.
A1  - Lichter, Peter
A1  - Chavez, Lukas
A1  - Zapatka, Marc
A1  - Pfister, Stefan M.
T1  - The landscape of genomic alterations across childhood cancers
JF  - Nature
N2  - Pan-cancer analyses that examine commonalities and differences among various cancer types have emerged as a powerful way to obtain novel insights into cancer biology. Here we present a comprehensive analysis of genetic alterations in a pan-cancer cohort including 961 tumours from children, adolescents, and young adults, comprising 24 distinct molecular types of cancer. Using a standardized workflow, we identified marked differences in terms of mutation frequency and significantly mutated genes in comparison to previously analysed adult cancers. Genetic alterations in 149 putative cancer driver genes separate the tumours into two classes: small mutation and structural/copy-number variant (correlating with germline variants). Structural variants, hyperdiploidy, and chromothripsis are linked to TP53 mutation status and mutational signatures. Our data suggest that 7–8% of the children in this cohort carry an unambiguous predisposing germline variant and that nearly 50% of paediatric neoplasms harbour a potentially druggable event, which is highly relevant for the design of future clinical trials.
KW  - cancer genomics
KW  - oncogenesis
KW  - paediatric cancer
KW  - predictive markers
KW  - translational research
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-229579
VL  - 555
ER  - 
TY  - JOUR
A1  - Franchini, Paolo
A1  - Jones, Julia C.
A1  - Xiong, Peiwen
A1  - Kneitz, Susanne
A1  - Gompert, Zachariah
A1  - Warren, Wesley C.
A1  - Walter, Ronald B.
A1  - Meyer, Axel
A1  - Schartl, Manfred
T1  - Long-term experimental hybridisation results in the evolution of a new sex chromosome in swordtail fish
JF  - Nature Communications
N2  - The remarkable diversity of sex determination mechanisms known in fish may be fuelled by exceptionally high rates of sex chromosome turnovers or transitions. However, the evolutionary causes and genomic mechanisms underlying this variation and instability are yet to be understood. Here we report on an over 30-year evolutionary experiment in which we tested the genomic consequences of hybridisation and selection between two Xiphophorus fish species with different sex chromosome systems. We find that introgression and imposing selection for pigmentation phenotypes results in the retention of an unexpectedly large maternally derived genomic region. During the hybridisation process, the sex-determining region of the X chromosome from one parental species was translocated to an autosome in the hybrids leading to the evolution of a new sex chromosome. Our results highlight the complexity of factors contributing to patterns observed in hybrid genomes, and we experimentally demonstrate that hybridisation can catalyze rapid evolution of a new sex chromosome.
KW  - evolutionary genetics
KW  - experimental evolution
KW  - genome evolution
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-228396
VL  - 9
ER  - 
TY  - JOUR
A1  - Jones, Julia C.
A1  - Fruciano, Carmelo
A1  - Keller, Anja
A1  - Schartl, Manfred
A1  - Meyer, Axel
T1  - Evolution of the elaborate male intromittent organ of Xiphophorus fishes
JF  - Ecology and Evolution
N2  - Internally fertilizing animals show a remarkable diversity in male genital morphology that is associated with sexual selection, and these traits are thought to be evolving particularly rapidly. Male fish in some internally fertilizing species have “gonopodia,” highly modified anal fins that are putatively important for sexual selection. However, our understanding of the evolution of genital diversity remains incomplete. Contrary to the prediction that male genital traits evolve more rapidly than other traits, here we show that gonopodial traits and other nongonopodial traits exhibit similar evolutionary rates of trait change and also follow similar evolutionary models in an iconic genus of poeciliid fish (Xiphophorus spp.). Furthermore, we find that both mating and nonmating natural selection mechanisms are unlikely to be driving the diverse Xiphophorus gonopodial morphology. Putative holdfast features of the male genital organ do not appear to be influenced by water flow, a candidate selective force in aquatic habitats. Additionally, interspecific divergence in gonopodial morphology is not significantly higher between sympatric species, than between allopatric species, suggesting that male genitals have not undergone reproductive character displacement. Slower rates of evolution in gonopodial traits compared with a subset of putatively sexually selected nongenital traits suggest that different selection mechanisms may be acting on the different trait types. Further investigations of this elaborate trait are imperative to determine whether it is ultimately an important driver of speciation.
KW  - Male intromittent organ
KW  - reproductive character displacement
KW  - sexual selection
KW  - species diversification
KW  - Xiphophorus fish
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-164956
VL  - 6
IS  - 20
ER  - 
TY  - JOUR
A1  - Strohmann, C.
A1  - Bauerecker, S.
A1  - Cammenga, H. K.
A1  - Jones, P. G.
A1  - Mutschler, E.
A1  - Lambrecht, G.
A1  - Tacke, Reinhold
T1  - Enantiomers of the muscarinic antagonist 1-cyclohexyl-1-(4-fluorophenyl)-4-piperidino-1-butanol (p-fluoro-hexahydro-difenidol): synthesis, absolute configuration, and enantiomeric purity
N2  - The enantiomers of the antimuscarinic agent 1-cyclohexyl-1- (4-fluorophenyl)-4-piperidino-1-butanol [(R)- and (S)-p-fluorohexahydro- difenidol] ((R)- and (S)-2a] and their methiodides (R)- 3 and (S)-3 were prepared with high enantiomeric purity. (R)- 2a and (S)-2a (isolated as hydrochlorides) were obtained by catalytic hydrogenation (Pd/C contact) of the corresponding enantiomers of 1-cyclohexyl-1-( 4-fl uorophen yl)-4-piperidino- 2-butyn-1-ol [(R)- and (S)-4]. Reaction of (R)-2a and (S)-2a with rnethyl iodide led to (R)-3 and (S)-3, respectively. The unsaturated precursors (R)- and (S}-4 (enantiorneric purity ~ 99.80 and ~99.94% e.e.; calorimetric analysis) were prepared by res-sepaolution of rac-4 [available from 4-FC\(_6\)H\(_4\)C(O)C\(_6\)H\(_{11}\) by reaction with LiC ~ CCH\(_2\)NC\(_5\)H\(_{10}\)] using (R)- and (S)-mandelic acid as resolving agents. The absolute configurations of the (R) and (S) enantiomers of 2a, 3, and 4 were determined by an X-ray crystal-structure analysis of (S)-5, the methiodide of (S)-4. (R)- 2a and (R)-3 exhibit a higher affinity for muscarinic M1, M2, M3, and M4 receptors (by up to two orders of magnitude) than their corresponding antipodes (S)-2a and (S)-3, the degree of stereoselectivity depending on the receptor subtype involved. (R)-2a represents a useful tool for rnuscarinic receptor research (affinity profile: M1 ~ M3 ~ M4 > M2).
KW  - Anorganische Chemie
KW  - Difenidol
KW  - p-fluoro-hexahydro-
KW  - enantiomers of / Muscarinic receptors
KW  - subtypes of
Y1  - 1991
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-64144
ER  - 
TY  - JOUR
A1  - Hempelmann, Alexander
A1  - Hartleb, Laura
A1  - van Straaten, Monique
A1  - Hashemi, Hamidreza
A1  - Zeelen, Johan P.
A1  - Bongers, Kevin
A1  - Papavasiliou, F. Nina
A1  - Engstler, Markus
A1  - Stebbins, C. Erec
A1  - Jones, Nicola G.
T1  - Nanobody-mediated macromolecular crowding induces membrane fission and remodeling in the African trypanosome
JF  - Cell Reports
N2  - The dense variant surface glycoprotein (VSG) coat of African trypanosomes represents the primary host-pathogen interface. Antigenic variation prevents clearing of the pathogen by employing a large repertoire of antigenically distinct VSG genes, thus neutralizing the host’s antibody response. To explore the epitope space of VSGs, we generate anti-VSG nanobodies and combine high-resolution structural analysis of VSG-nanobody complexes with binding assays on living cells, revealing that these camelid antibodies bind deeply inside the coat. One nanobody causes rapid loss of cellular motility, possibly due to blockage of VSG mobility on the coat, whose rapid endocytosis and exocytosis are mechanistically linked to Trypanosoma brucei propulsion and whose density is required for survival. Electron microscopy studies demonstrate that this loss of motility is accompanied by rapid formation and shedding of nanovesicles and nanotubes, suggesting that increased protein crowding on the dense membrane can be a driving force for membrane fission in living cells.
KW  - African trypanosome
KW  - host-pathogen interaction
KW  - variant surface glycoproteins
KW  - immune epitope mapping
KW  - structural biology
KW  - nanovesicle formation
KW  - nanotube formation
KW  - protein crowding
KW  - membrane fission
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-270285
VL  - 37
IS  - 5
ER  -