232 results on '"Rippe K"'
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2. Pan-mutant-IDH1 inhibitor BAY1436032 is highly effective against human IDH1 mutant acute myeloid leukemia in vivo
- Author
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Chaturvedi, A, Herbst, L, Pusch, S, Klett, L, Goparaju, R, Stichel, D, Kaulfuss, S, Panknin, O, Zimmermann, K, Toschi, L, Neuhaus, R, Haegebarth, A, Rehwinkel, H, Hess-Stumpp, H, Bauser, M, Bochtler, T, Struys, E A, Sharma, A, Bakkali, A, Geffers, R, Araujo-Cruz, M M, Thol, F, Gabdoulline, R, Ganser, A, Ho, A D, von Deimling, A, Rippe, K, Heuser, M, and Krämer, A
- Published
- 2017
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3. Author Correction: Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples
- Author
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Bailey M. H., Meyerson W. U., Dursi L. J., Wang L. -B., Dong G., Liang W. -W., Weerasinghe A., Li S., Li Y., Kelso S., Akbani R., Anur P., Buchanan A., Chiotti K., Covington K., Creason A., Ding L., Ellrott K., Fan Y., Foltz S., Getz G., Hale W., Haussler D., Hess J. M., Hutter C. M., Kandoth C., Kasaian K., Kasapi M., Larson D., Leshchiner I., Letaw J., Ma S., McLellan M. D., Men Y., Mills G. B., Niu B., Peto M., Radenbaugh A., Reynolds S. M., Saksena G., Sofia H., Stewart C., Struck A. J., Stuart J. M., Wang W., Weinstein J. N., Wheeler D. A., Wong C. K., Xi L., Ye K., Bieg M., Boutros P. C., Buchhalter I., Butler A. P., Chen K., Chong Z., Drechsel O., Jonathan Dursi L., Eils R., Espiritu S. M. G., Fulton R. S., Gao S., Gelpi J. L., Gerstein M. B., Gonzalez S., Gut I. G., Hach F., Heinold M. C., Hinton J., Hu T., Huang V., Huang Y., Hutter B., Jones D. R., Jung J., Jager N., Kim H. -L., Kleinheinz K., Kumar S., Kumar Y., Lalansingh C. M., Letunic I., Livitz D., Ma E. Z., Maruvka Y. E., Mashl R. J., Menzies A., Milovanovic A., Nielsen M. M., Ossowski S., Paramasivam N., Pedersen J. S., Perry M. D., Puiggros M., Raine K. M., Rheinbay E., Royo R., Sahinalp S. C., Sarrafi I., Schlesner M., Simpson J. T., Stebbings L., Stobbe M. D., Teague J. W., Tiao G., Torrents D., Wala J. A., Wang J., Waszak S. M., Weischenfeldt J., Wendl M. C., Werner J., Wu Z., Xue H., Yakneen S., Yamaguchi T. N., Yellapantula V. D., Yung C. K., Zhang J., Aaltonen L. A., Abascal F., Abeshouse A., Aburatani H., Adams D. J., Agrawal N., Ahn K. S., Ahn S. -M., Aikata H., Akdemir K. C., Al-Ahmadie H., Al-Sedairy S. T., Al-Shahrour F., Alawi M., Albert M., Aldape K., Alexandrov L. B., Ally A., Alsop K., Alvarez E. G., Amary F., Amin S. B., Aminou B., Ammerpohl O., Anderson M. J., Ang Y., Antonello D., Aparicio S., Appelbaum E. L., Arai Y., Aretz A., Arihiro K., Ariizumi S. -I., Armenia J., Arnould L., Asa S., Assenov Y., Atwal G., Aukema S., Auman J. T., Aure M. R., Awadalla P., Aymerich M., Bader G. D., Baez-Ortega A., Bailey P. J., Balasundaram M., Balu S., Bandopadhayay P., Banks R. E., Barbi S., Barbour A. P., Barenboim J., Barnholtz-Sloan J., Barr H., Barrera E., Bartlett J., Bartolome J., Bassi C., Bathe O. F., Baumhoer D., Bavi P., Baylin S. B., Bazant W., Beardsmore D., Beck T. A., Behjati S., Behren A., Bell C., Beltran S., Benz C., Berchuck A., Bergmann A. K., Bergstrom E. N., Berman B. P., Berney D. M., Bernhart S. H., Beroukhim R., Berrios M., Bersani S., Bertl J., Betancourt M., Bhandari V., Bhosle S. G., Biankin A. V., Bigner D., Binder H., Birney E., Birrer M., Biswas N. K., Bjerkehagen B., Bodenheimer T., Boice L., Bonizzato G., De Bono J. S., Boot A., Bootwalla M. S., Borg A., Borkhardt A., Boroevich K. A., Borozan I., Borst C., Bosenberg M., Bosio M., Boultwood J., Bourque G., Bova G. S., Bowen D. T., Bowlby R., Bowtell D. D. L., Boyault S., Boyce R., Boyd J., Brazma A., Brennan P., Brewer D. S., Brinkman A. B., Bristow R. G., Broaddus R. R., Brock J. E., Brock M., Broeks A., Brooks A. N., Brooks D., Brors B., Brunak S., Bruxner T. J. C., Bruzos A. L., Buchholz C., Bullman S., Burke H., Burkhardt B., Burns K. H., Busanovich J., Bustamante C. D., Butte A. J., Byrne N. J., Borresen-Dale A. -L., Caesar-Johnson S. J., Cafferkey A., Cahill D., Calabrese C., Caldas C., Calvo F., Camacho N., Campbell P. J., Campo E., Cantu C., Cao S., Carey T. E., Carlevaro-Fita J., Carlsen R., Cataldo I., Cazzola M., Cebon J., Cerfolio R., Chadwick D. E., Chakravarty D., Chalmers D., Chan C. W. Y., Chan K., Chan-Seng-Yue M., Chandan V. S., Chang D. K., Chanock S. J., Chantrill L. A., Chateigner A., Chatterjee N., Chayama K., Chen H. -W., Chen J., Chen Y., Chen Z., Cherniack A. D., Chien J., Chiew Y. -E., Chin S. -F., Cho J., Cho S., Choi J. K., Choi W., Chomienne C., Choo S. P., Chou A., Christ A. N., Christie E. L., Chuah E., Cibulskis C., Cibulskis K., Cingarlini S., Clapham P., Claviez A., Cleary S., Cloonan N., Cmero M., Collins C. C., Connor A. A., Cooke S. L., Cooper C. S., Cope L., Corbo V., Cordes M. G., Cordner S. M., Cortes-Ciriano I., Cowin P. A., Craft B., Craft D., Creighton C. J., Cun Y., Curley E., Cutcutache I., Czajka K., Czerniak B., Dagg R. A., Danilova L., Davi M. V., Davidson N. R., Davies H., Davis I. J., Davis-Dusenbery B. N., Dawson K. J., De La Vega F. M., De Paoli-Iseppi R., Defreitas T., Dei Tos A. P., Delaneau O., Demchok J. A., Demeulemeester J., Demidov G. M., Demircioglu D., Dennis N. M., Denroche R. E., Dentro S. C., Desai N., Deshpande V., Deshwar A. G., Desmedt C., Deu-Pons J., Dhalla N., Dhani N. C., Dhingra P., Dhir R., DiBiase A., Diamanti K., Ding S., Dinh H. Q., Dirix L., Doddapaneni H. V., Donmez N., Dow M. T., Drapkin R., Drews R. M., Serge S., Dudderidge T., Dueso-Barroso A., Dunford A. J., Dunn M., Duthie F. R., Dutton-Regester K., Eagles J., Easton D. F., Edmonds S., Edwards P. A., Edwards S. E., Eeles R. A., Ehinger A., Eils J., El-Naggar A., Eldridge M., Erkek S., Escaramis G., Estivill X., Etemadmoghadam D., Eyfjord J. E., Faltas B. M., Fan D., Faquin W. C., Farcas C., Fassan M., Fatima A., Favero F., Fayzullaev N., Felau I., Fereday S., Ferguson M. L., Ferretti V., Feuerbach L., Field M. A., Fink J. L., Finocchiaro G., Fisher C., Fittall M. W., Fitzgerald A., Fitzgerald R. C., Flanagan A. M., Fleshner N. E., Flicek P., Foekens J. A., Fong K. M., Fonseca N. A., Foster C. S., Fox N. S., Fraser M., Frazer S., Frenkel-Morgenstern M., Friedman W., Frigola J., Fronick C. C., Fujimoto A., Fujita M., Fukayama M., Fulton L. A., Furuta M., Futreal P. A., Fullgrabe A., Gabriel S. B., Gallinger S., Gambacorti Passerini C., Gao J., Garraway L., Garred O., Garrison E., Garsed D. W., Gehlenborg N., George J., Gerhard D. S., Gerhauser C., Gershenwald J. E., Gerstung M., Ghori M., Ghossein R., Giama N. H., Gibbs R. A., Gill A. J., Gill P., Giri D. D., Glodzik D., Gnanapragasam V. J., Goebler M. E., Goldman M. J., Gomez C., Gonzalez-Perez A., Gordenin D. A., Gossage J., Gotoh K., Govindan R., Grabau D., Graham J. S., Grant R. C., Green A. R., Green E., Greger L., Grehan N., Grimaldi S., Grimmond S. M., Grossman R. L., Grundhoff A., Gundem G., Guo Q., Gupta M., Gupta S., Gut M., Goke J., Ha G., Haake A., Haan D., Haas S., Haase K., Haber J. E., Habermann N., Haider S., Hama N., Hamdy F. C., Hamilton A., Hamilton M. P., Han L., Hanna G. B., Hansmann M., Haradhvala N. J., Harismendy O., Harliwong I., Harmanci A. O., Harrington E., Hasegawa T., Hawkins S., Hayami S., Hayashi S., Hayes D. N., Hayes S. J., Hayward N. K., Hazell S., He Y., Heath A. P., Heath S. C., Hedley D., Hegde A. M., Heiman D. I., Heins Z., Heisler L. E., Hellstrom-Lindberg E., Helmy M., Heo S. G., Hepperla A. J., Heredia-Genestar J. M., Herrmann C., Hersey P., Hilmarsdottir H., Hirano S., Hiraoka N., Hoadley K. A., Hobolth A., Hodzic E., Hoell J. I., Hoffmann S., Hofmann O., Holbrook A., Holik A. Z., Hollingsworth M. A., Holmes O., Holt R. A., Hong C., Hong E. P., Hong J. H., Hooijer G. K., Hornshoj H., Hosoda F., Hou Y., Hovestadt V., Howat W., Hoyle A. P., Hruban R. H., Hu J., Hua X., Huang K. -L., Huang M., Huang M. N., Huber W., Hudson T. J., Hummel M., Hung J. A., Huntsman D., Hupp T. R., Huse J., Huska M. R., Hubschmann D., Iacobuzio-Donahue C. A., Imbusch C. D., Imielinski M., Imoto S., Isaacs W. B., Isaev K., Ishikawa S., Iskar M., Islam S. M. A., Ittmann M., Ivkovic S., Izarzugaza J. M. G., Jacquemier J., Jakrot V., Jamieson N. B., Jang G. H., Jang S. J., Jayaseelan J. C., Jayasinghe R., Jefferys S. R., Jegalian K., Jennings J. L., Jeon S. -H., Jerman L., Ji Y., Jiao W., Johansson P. A., Johns A. L., Johns J., Johnson R., Johnson T. A., Jolly C., Joly Y., Jonasson J. G., Jones C. D., Jones D. T. W., Jones N., Jones S. J. M., Jonkers J., Ju Y. S., Juhl H., Juul M., Juul R. I., Juul S., Kabbe R., Kahles A., Kahraman A., Kaiser V. B., Kakavand H., Kalimuthu S., von Kalle C., Kang K. J., Karaszi K., Karlan B., Karlic R., Karsch D., Kassahn K. S., Katai H., Kato M., Katoh H., Kawakami Y., Kay J. D., Kazakoff S. H., Kazanov M. D., Keays M., Kebebew E., Kefford R. F., Kellis M., Kench J. G., Kennedy C. J., Kerssemakers J. N. A., Khoo D., Khoo V., Khuntikeo N., Khurana E., Kilpinen H., Kim H. K., Kim H. -Y., Kim H., Kim J., Kim J. K., Kim Y., King T. A., Klapper W., Klimczak L. J., Knappskog S., Kneba M., Knoppers B. M., Koh Y., Jan Komorowski, Komura D., Komura M., Kong G., Kool M., Korbel J. O., Korchina V., Korshunov A., Koscher M., Koster R., Kote-Jarai Z., Koures A., Kovacevic M., Kremeyer B., Kretzmer H., Kreuz M., Krishnamurthy S., Kube D., Kumar K., Kumar P., Kundra R., Kubler K., Kuppers R., Lagergren J., Lai P. H., Laird P. W., Lakhani S. R., Lalonde E., Lamaze F. C., Lambert A., Lander E., Landgraf P., Landoni L., Langerod A., Lanzos A., Larsimont D., Larsson E., Lathrop M., Lau L. M. S., Lawerenz C., Lawlor R. T., Lawrence M. S., Lazar A. J., Le X., Lee D., Lee E. A., Lee H. J., Lee J. J. -K., Lee J. -Y., Lee J., Lee M. T. M., Lee-Six H., Lehmann K. -V., Lehrach H., Lenze D., Leonard C. R., Leongamornlert D. A., Letourneau L., Levine D. A., Lewis L., Ley T., Li C., Li C. H., Li H. I., Li J., Li L., Li X., Liang H., Liang S. -B., Lichter P., Lin P., Lin Z., Linehan W. M., Lingjaerde O. C., Liu D., Liu E. M., Liu F. -F., Liu F., Liu J., Liu X., Livingstone J., Livni N., Lochovsky L., Loeffler M., Long G. V., Lopez-Guillermo A., Lou S., Louis D. N., Lovat L. B., Lu Y., Lu Y. -J., Luchini C., Lungu I., Luo X., Luxton H. J., Lynch A. G., Lype L., Lopez C., Lopez-Otin C., Ma Y., MacGrogan G., MacRae S., Macintyre G., Madsen T., Maejima K., Mafficini A., Maglinte D. T., Maitra A., Majumder P. P., Malcovati L., Malikic S., Malleo G., Mann G. J., Mantovani-Loffler L., Marchal K., Marchegiani G., Mardis E. R., Margolin A. A., Marin M. G., Markowetz F., Markowski J., Marks J., Marques-Bonet T., Marra M. A., Marsden L., Martens J. W. M., Martin S., Martin-Subero J. I., Martincorena I., Martinez-Fundichely A., Massie C. E., Matthew T. J., Matthews L., Mayer E., Mayes S., Mayo M., Mbabaali F., McCune K., McDermott U., McGillivray P. D., McPherson J. D., McPherson J. R., McPherson T. A., Meier S. R., Meng A., Meng S., Merrett N. D., Merson S., Meyerson M., Mieczkowski P. A., Mihaiescu G. L., Mijalkovic S., Mijalkovic-Lazic A. M., Mikkelsen T., Milella M., Mileshkin L., Miller C. A., Miller D. K., Miller J. K., Minner S., Miotto M., Arnau G. M., Mirabello L., Mitchell C., Mitchell T. J., Miyano S., Miyoshi N., Mizuno S., Molnar-Gabor F., Moore M. J., Moore R. A., Morganella S., Morris Q. D., Morrison C., Mose L. E., Moser C. D., Muinos F., Mularoni L., Mungall A. J., Mungall K., Musgrove E. A., Mustonen V., Mutch D., Muyas F., Muzny D. M., Munoz A., Myers J., Myklebost O., Moller P., Nagae G., Nagrial A. M., Nahal-Bose H. K., Nakagama H., Nakagawa H., Nakamura H., Nakamura T., Nakano K., Nandi T., Nangalia J., Nastic M., Navarro A., Navarro F. C. P., Neal D. E., Nettekoven G., Newell F., Newhouse S. J., Newton Y., Ng A. W. T., Ng A., Nicholson J., Nicol D., Nie Y., Nielsen G. P., Nik-Zainal S., Noble M. S., Nones K., Northcott P. A., Notta F., O'Connor B. D., O'Donnell P., O'Donovan M., O'Meara S., O'Neill B. P., O'Neill J. R., Ocana D., Ochoa A., Oesper L., Ogden C., Ohdan H., Ohi K., Ohno-Machado L., Oien K. A., Ojesina A. I., Ojima H., Okusaka T., Omberg L., Ong C. K., Ott G., Ouellette B. F. F., P'ng C., Paczkowska M., Paiella S., Pairojkul C., Pajic M., Pan-Hammarstrom Q., Papaemmanuil E., Papatheodorou I., Park J. W., Park J. -W., Park K., Park P. J., Parker J. S., Parsons S. L., Pass H., Pasternack D., Pastore A., Patch A. -M., Pauporte I., Pea A., Pearson J. V., Pedamallu C. S., Pederzoli P., Peifer M., Pennell N. A., Perou C. M., Petersen G. M., Petrelli N., Petryszak R., Pfister S. M., Phillips M., Pich O., Pickett H. A., Pihl T. D., Pillay N., Pinder S., Pinese M., Pinho A. V., Pitkanen E., Pivot X., Pineiro-Yanez E., Planko L., Plass C., Polak P., Pons T., Popescu I., Potapova O., Prasad A., Preston S. R., Prinz M., Pritchard A. L., Prokopec S. D., Provenzano E., Puente X. S., Puig S., Pulido-Tamayo S., Pupo G. M., Purdie C. A., Quinn M. C., Rabionet R., Rader J. S., Radlwimmer B., Radovic P., Raeder B., Ramakrishna M., Ramakrishnan K., Ramalingam S., Raphael B. J., Rathmell W. K., Rausch T., Reifenberger G., Reimand J., Reis-Filho J., Reuter V., Reyes-Salazar I., Reyna M. A., Riazalhosseini Y., Richardson A. L., Richter J., Ringel M., Ringner M., Rino Y., Rippe K., Roach J., Roberts L. R., Roberts N. D., Roberts S. A., Robertson A. G., Robertson A. J., Rodriguez J. B., Rodriguez-Martin B., Rodriguez-Gonzalez F. G., Roehrl M. H. A., Rohde M., Rokutan H., Romieu G., Rooman I., Roques T., Rosebrock D., Rosenberg M., Rosenstiel P. C., Rosenwald A., Rowe E. W., Rozen S. G., Rubanova Y., Rubin M. A., Rubio-Perez C., Rudneva V. A., Rusev B. C., Ruzzenente A., Ratsch G., Sabarinathan R., Sabelnykova V. Y., Sadeghi S., Saini N., Saito-Adachi M., Salcedo A., Salgado R., Salichos L., Sallari R., Saller C., Salvia R., Sam M., Samra J. S., Sanchez-Vega F., Sander C., Sanders G., Sarin R., Sasaki-Oku A., Sauer T., Sauter G., Saw R. P. M., Scardoni M., Scarlett C. J., Scarpa A., Scelo G., Schadendorf D., Schein J. E., Schilhabel M. B., Schlomm T., Schmidt H. K., Schramm S. -J., Schreiber S., Schultz N., Schumacher S. E., Schwarz R. F., Scolyer R. A., Scott D., Scully R., Seethala R., Segre A. V., Selander I., Semple C. A., Senbabaoglu Y., Sengupta S., Sereni E., Serra S., Sgroi D. C., Shackleton M., Shah N. C., Shahabi S., Shang C. A., Shang P., Shapira O., Shelton T., Shen C., Shen H., Shepherd R., Shi R., Shi Y., Shiah Y. -J., Shibata T., Shih J., Shimizu E., Shimizu K., Shin S. J., Shiraishi Y., Shmaya T., Shmulevich I., Shorser S. I., Short C., Shrestha R., Shringarpure S. S., Shriver C., Shuai S., Sidiropoulos N., Siebert R., Sieuwerts A. M., Sieverling L., Signoretti S., Sikora K. O., Simbolo M., Simon R., Simons J. V., Singer S., Sinnott-Armstrong N., Sipahimalani P., Skelly T. J., Smid M., Smith J., Smith-McCune K., Socci N. D., Sofia H. J., Soloway M. G., Song L., Sood A. K., Sothi S., Sotiriou C., Soulette C. M., Span P. N., Spellman P. T., Sperandio N., Spillane A. J., Spiro O., Spring J., Staaf J., Stadler P. F., Staib P., Stark S. G., Stefansson O. A., Stegle O., Stein L. D., Stenhouse A., Stilgenbauer S., Stratton M. R., Stretch J. R., Stunnenberg H. G., Su H., Su X., Sun R. X., Sungalee S., Susak H., Suzuki A., Sweep F., Szczepanowski M., Sultmann H., Yugawa T., Tam A., Tamborero D., Tan B. K. T., Tan D., Tan P., Tanaka H., Taniguchi H., Tanskanen T. J., Tarabichi M., Tarnuzzer R., Tarpey P., Taschuk M. L., Tatsuno K., Tavare S., Taylor D. F., Taylor-Weiner A., Teh B. T., Tembe V., Temes J., Thai K., Thayer S. P., Thiessen N., Thomas G., Thomas S., Thompson A., Thompson A. M., Thompson J. F., Thompson R. H., Thorne H., Thorne L. B., Thorogood A., Tijanic N., Timms L. E., Tirabosco R., Tojo M., Tommasi S., Toon C. W., Toprak U. H., Tortora G., Tost J., Totoki Y., Townend D., Traficante N., Treilleux I., Trotta J. -R., Trumper L. H. P., Tsao M., Tsunoda T., Tubio J. M. C., Tucker O., Turkington R., Turner D. J., Tutt A., Ueno M., Ueno N. T., Umbricht C., Umer H. M., Underwood T. J., Urban L., Urushidate T., Ushiku T., Uuskula-Reimand L., Valencia A., Van Den Berg D. J., Van Laere S., Van Loo P., Van Meir E. G., Van den Eynden G. G., Van der Kwast T., Vasudev N., Vazquez M., Vedururu R., Veluvolu U., Vembu S., Verbeke L. P. C., Vermeulen P., Verrill C., Viari A., Vicente D., Vicentini C., Raghavan K. V., Viksna J., Vilain R. E., Villasante I., Vincent-Salomon A., Visakorpi T., Voet D., Vyas P., Vazquez-Garcia I., Waddell N. M., Waddell N., Wadelius C., Wadi L., Wagener R., Wang L., Wang Q., Wang Y., Wang Z., Waring P. M., Warnatz H. -J., Warrell J., Warren A. Y., Wedge D. C., Weichenhan D., Weinberger P., Weisenberger D. J., Welch I., Whalley J. P., Whitaker H. C., Wigle D., Wilkerson M. D., Williams A., Wilmott J. S., Wilson G. W., Wilson J. M., Wilson R. K., Winterhoff B., Wintersinger J. A., Wiznerowicz M., Wolf S., Wong B. H., Wong T., Wong W., Woo Y., Wood S., Wouters B. G., Wright A. J., Wright D. W., Wright M. H., Wu C. -L., Wu D. -Y., Wu G., Wu J., Wu K., Wu Y., Xia T., Xiang Q., Xiao X., Xing R., Xiong H., Xu Q., Xu Y., Yachida S., Yamaguchi R., Yamamoto M., Yamamoto S., Yamaue H., Yang F., Yang H., Yang J. Y., Yang L., Yang S., Yang T. -P., Yang Y., Yao X., Yaspo M. -L., Yates L., Yau C., Ye C., Yoon C. J., Yoon S. -S., Yousif F., Yu J., Yu K., Yu W., Yu Y., Yuan K., Yuan Y., Yuen D., Zaikova O., Zamora J., Zapatka M., Zenklusen J. C., Zenz T., Zeps N., Zhang C. -Z., Zhang F., Zhang H., Zhang X., Zhang Y., Zhang Z., Zhao Z., Zheng L., Zheng X., Zhou W., Zhou Y., Bin Zhu, Zhu H., Zhu J., Zhu S., Zou L., Zou X., deFazio A., van As N., van Deurzen C. H. M., van de Vijver M. J., van't Veer L., von Mering C., Bailey, M, Meyerson, W, Dursi, L, Wang, L, Dong, G, Liang, W, Weerasinghe, A, Li, S, Li, Y, Kelso, S, Akbani, R, Anur, P, Buchanan, A, Chiotti, K, Covington, K, Creason, A, Ding, L, Ellrott, K, Fan, Y, Foltz, S, Getz, G, Hale, W, Haussler, D, Hess, J, Hutter, C, Kandoth, C, Kasaian, K, Kasapi, M, Larson, D, Leshchiner, I, Letaw, J, Ma, S, Mclellan, M, Men, Y, Mills, G, Niu, B, Peto, M, Radenbaugh, A, Reynolds, S, Saksena, G, Sofia, H, Stewart, C, Struck, A, Stuart, J, Wang, W, Weinstein, J, Wheeler, D, Wong, C, Xi, L, Ye, K, Bieg, M, Boutros, P, Buchhalter, I, Butler, A, Chen, K, Chong, Z, Drechsel, O, Jonathan Dursi, L, Eils, R, Espiritu, S, Fulton, R, Gao, S, Gelpi, J, Gerstein, M, Gonzalez, S, Gut, I, Hach, F, Heinold, M, Hinton, J, Hu, T, Huang, V, Huang, Y, Hutter, B, Jones, D, Jung, J, Jager, N, Kim, H, Kleinheinz, K, Kumar, S, Kumar, Y, Lalansingh, C, Letunic, I, Livitz, D, Ma, E, Maruvka, Y, Mashl, R, Menzies, A, Milovanovic, A, Nielsen, M, 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Science ,MEDLINE ,Medizin ,General Physics and Astronomy ,Pain ,610 Medicine & health ,1600 General Chemistry ,Computational biology ,Biology ,10 kHz spinal cord stimulation ,Genome ,responders ,MC3 Working Group ,General Biochemistry, Genetics and Molecular Biology ,whole exome sequencing ,Machine Learning ,1300 General Biochemistry, Genetics and Molecular Biology ,PCAWG novel somatic mutation calling methods working group ,medicine ,cancer ,Genome mutation ,Exome ,Exome sequencing ,Whole genome sequencing ,whole genome sequencing ,Multidisciplinary ,Published Erratum ,Cancer ,PCAWG Consortium ,General Chemistry ,medicine.disease ,3100 General Physics and Astronomy ,oncology ,10032 Clinic for Oncology and Hematology ,Prediction - Abstract
Weitere Nicht-UDE-Autoren sind nicht genannt. Originalpublikation: 10.1038/s41467-020-18151-y. CA extern The original version of this Article omitted from the author list the 9th author Yize Li, who is from the ‘The McDonnell Genome Institute at Washington University, St. Louis, MO 63108, USA and Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, MO 63108, USA’. This has been corrected in both the PDF and HTML versions of the Article. © 2020, The Author(s).
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- 2020
4. Sex differences in oncogenic mutational processes
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Li C. H., Prokopec S. D., Sun R. X., Yousif F., Schmitz N., Al-Shahrour F., Atwal G., Bailey P. J., Biankin A. V., Boutros P. C., Campbell P. J., Chang D. K., Cooke S. L., Deshpande V., Faltas B. M., Faquin W. C., Garraway L., Getz G., Grimmond S. M., Haider S., Hoadley K. A., Jiao W., Kaiser V. B., Karlic R., Kato M., Kubler K., Lazar A. J., Louis D. N., Margolin A., Martin S., Nahal-Bose H. K., Nielsen G. P., Nik-Zainal S., Omberg L., P'ng C., Perry M. D., Polak P., Rheinbay E., Rubin M. A., Semple C. A., Sgroi D. C., Shibata T., Siebert R., Smith J., Stein L. D., Stobbe M. D., Thai K., Wright D. W., Wu C. -L., Yuan K., Zhang J., Aaltonen L. A., Abascal F., Abeshouse A., Aburatani H., Adams D. J., Agrawal N., Ahn K. S., Ahn S. -M., Aikata H., Akbani R., Akdemir K. C., Al-Ahmadie H., Al-Sedairy S. T., Alawi M., Albert M., Aldape K., Alexandrov L. B., Ally A., Alsop K., Alvarez E. G., Amary F., Amin S. B., Aminou B., Ammerpohl O., Anderson M. J., Ang Y., Antonello D., Anur P., Aparicio S., Appelbaum E. L., Arai Y., Aretz A., Arihiro K., Ariizumi S. -I., Armenia J., Arnould L., Asa S., Assenov Y., Aukema S., Auman J. T., Aure M. R., Awadalla P., Aymerich M., Bader G. D., Baez-Ortega A., Bailey M. H., Balasundaram M., Balu S., Bandopadhayay P., Banks R. E., Barbi S., Barbour A. P., Barenboim J., Barnholtz-Sloan J., Barr H., Barrera E., Bartlett J., Bartolome J., Bassi C., Bathe O. F., Baumhoer D., Bavi P., Baylin S. B., Bazant W., Beardsmore D., Beck T. A., Behjati S., Behren A., Niu B., Bell C., Beltran S., Benz C., Berchuck A., Bergmann A. K., Bergstrom E. N., Berman B. P., Berney D. M., Bernhart S. H., Beroukhim R., Berrios M., Bersani S., Bertl J., Betancourt M., Bhandari V., Bhosle S. G., Bieg M., Bigner D., Binder H., Birney E., Birrer M., Biswas N. K., Bjerkehagen B., Bodenheimer T., Boice L., Bonizzato G., De Bono J. S., Boot A., Bootwalla M. S., Borg A., Borkhardt A., Boroevich K. A., Borozan I., Borst C., Bosenberg M., Bosio M., Boultwood J., Bourque G., Bova G. S., Bowen D. T., Bowlby R., Bowtell D. D. L., Boyault S., Boyce R., Boyd J., Brazma A., Brennan P., Brewer D. S., Brinkman A. B., Bristow R. G., Broaddus R. R., Brock J. E., Brock M., Broeks A., Brooks A. N., Brooks D., Brors B., Brunak S., Bruxner T. J. C., Bruzos A. L., Buchanan A., Buchhalter I., Buchholz C., Bullman S., Burke H., Burkhardt B., Burns K. H., Busanovich J., Bustamante C. D., Butler A. P., Butte A. J., Byrne N. J., Borresen-Dale A. -L., Caesar-Johnson S. J., Cafferkey A., Cahill D., Calabrese C., Caldas C., Calvo F., Camacho N., Campo E., Cantu C., Cao S., Carey T. E., Carlevaro-Fita J., Carlsen R., Cataldo I., Cazzola M., Cebon J., Cerfolio R., Chadwick D. E., Chakravarty D., Chalmers D., Chan C. W. Y., Chan K., Chan-Seng-Yue M., Chandan V. S., Chanock S. J., Chantrill L. A., Chateigner A., Chatterjee N., Chayama K., Chen H. -W., Chen J., Chen K., Chen Y., Chen Z., Cherniack A. D., Chien J., Chiew Y. -E., Chin S. -F., Cho J., Cho S., Choi J. K., Choi W., Chomienne C., Chong Z., Choo S. P., Chou A., Christ A. N., Christie E. L., Chuah E., Cibulskis C., Cibulskis K., Cingarlini S., Clapham P., Claviez A., Cleary S., Cloonan N., Cmero M., Collins C. C., Connor A. A., Cooper C. S., Cope L., Corbo V., Cordes M. G., Cordner S. M., Cortes-Ciriano I., Covington K., Cowin P. A., Craft B., Craft D., Creighton C. J., Cun Y., Curley E., Cutcutache I., Czajka K., Czerniak B., Dagg R. A., Danilova L., Davi M. V., Davidson N. R., Davies H., Davis I. J., Davis-Dusenbery B. N., Dawson K. J., De La Vega F. M., De Paoli-Iseppi R., Defreitas T., Dei Tos A. P., Delaneau O., Demchok J. A., Demeulemeester J., Demidov G. M., Demircioglu D., Dennis N. M., Denroche R. E., Dentro S. C., Desai N., Deshwar A. G., Desmedt C., Deu-Pons J., Dhalla N., Dhani N. C., Dhingra P., Dhir R., DiBiase A., Diamanti K., Ding L., Ding S., Dinh H. Q., Dirix L., Doddapaneni H. V., Donmez N., Dow M. T., Drapkin R., Drechsel O., Drews R. M., Serge S., Dudderidge T., Dueso-Barroso A., Dunford A. J., Dunn M., Dursi L. J., Duthie F. R., Dutton-Regester K., Eagles J., Easton D. F., Edmonds S., Edwards P. A., Edwards S. E., Eeles R. A., Ehinger A., Eils J., Eils R., El-Naggar A., Eldridge M., Ellrott K., Erkek S., Escaramis G., Espiritu S. M. G., Estivill X., Etemadmoghadam D., Eyfjord J. E., Fan D., Fan Y., Farcas C., Fassan M., Fatima A., Favero F., Fayzullaev N., Felau I., Fereday S., Ferguson M. L., Ferretti V., Feuerbach L., Field M. A., Fink J. L., Finocchiaro G., Fisher C., Fittall M. W., Fitzgerald A., Fitzgerald R. C., Flanagan A. M., Fleshner N. E., Flicek P., Foekens J. A., Fong K. M., Fonseca N. A., Foster C. S., Fox N. S., Fraser M., Frazer S., Frenkel-Morgenstern M., Friedman W., Frigola J., Fronick C. C., Fujimoto A., Fujita M., Fukayama M., Fulton L. A., Fulton R. S., Furuta M., Futreal P. A., Fullgrabe A., Gabriel S. B., Gallinger S., Gambacorti Passerini C., Gao J., Gao S., Garred O., Garrison E., Garsed D. W., Gehlenborg N., Gelpi J. L. L., George J., Gerhard D. S., Gerhauser C., Gershenwald J. E., Gerstein M., Gerstung M., Ghori M., Ghossein R., Giama N. H., Gibbs R. A., Gill A. J., Gill P., Giri D. D., Glodzik D., Gnanapragasam V. J., Goebler M. E., Goldman M. J., Gomez C., Gonzalez S., Gonzalez-Perez A., Gordenin D. A., Gossage J., Gotoh K., Govindan R., Grabau D., Graham J. S., Grant R. C., Green A. R., Green E., Greger L., Grehan N., Grimaldi S., Grossman R. L., Grundhoff A., Gundem G., Guo Q., Gupta M., Gupta S., Gut I. G., Gut M., Goke J., Ha G., Haake A., Haan D., Haas S., Haase K., Haber J. E., Habermann N., Hach F., Hama N., Hamdy F. C., Hamilton A., Hamilton M. P., Han L., Hanna G. B., Hansmann M., Haradhvala N. J., Harismendy O., Harliwong I., Harmanci A. O., Harrington E., Hasegawa T., Haussler D., Hawkins S., Hayami S., Hayashi S., Hayes D. N., Hayes S. J., Hayward N. K., Hazell S., He Y., Heath A. P., Heath S. C., Hedley D., Hegde A. M., Heiman D. I., Heinold M. C., Heins Z., Heisler L. E., Hellstrom-Lindberg E., Helmy M., Heo S. G., Hepperla A. J., Heredia-Genestar J. M., Herrmann C., Hersey P., Hess J. M., Hilmarsdottir H., Hinton J., Hirano S., Hiraoka N., Hobolth A., Hodzic E., Hoell J. I., Hoffmann S., Hofmann O., Holbrook A., Holik A. Z., Hollingsworth M. A., Holmes O., Holt R. A., Hong C., Hong E. P., Hong J. H., Hooijer G. K., Hornshoj H., Hosoda F., Hou Y., Hovestadt V., Howat W., Hoyle A. P., Hruban R. H., Hu J., Hu T., Hua X., Huang K. -L., Huang M., Huang M. N., Huang V., Huang Y., Huber W., Hudson T. J., Hummel M., Hung J. A., Huntsman D., Hupp T. R., Huse J., Huska M. R., Hutter B., Hutter C. M., Hubschmann D., Iacobuzio-Donahue C. A., Imbusch C. D., Imielinski M., Imoto S., Isaacs W. B., Isaev K., Ishikawa S., Iskar M., Islam S. M. A., Ittmann M., Ivkovic S., Izarzugaza J. M. G., Jacquemier J., Jakrot V., Jamieson N. B., Jang G. H., Jang S. J., Jayaseelan J. C., Jayasinghe R., Jefferys S. R., Jegalian K., Jennings J. L., Jeon S. -H., Jerman L., Ji Y., Johansson P. A., Johns A. L., Johns J., Johnson R., Johnson T. A., Jolly C., Joly Y., Jonasson J. G., Jones C. D., Jones D. R., Jones D. T. W., Jones N., Jones S. J. M., Jonkers J., Ju Y. S., Juhl H., Jung J., Juul M., Juul R. I., Juul S., Jager N., Kabbe R., Kahles A., Kahraman A., Kakavand H., Kalimuthu S., von Kalle C., Kang K. J., Karaszi K., Karlan B., Karsch D., Kasaian K., Kassahn K. S., Katai H., Katoh H., Kawakami Y., Kay J. D., Kazakoff S. H., Kazanov M. D., Keays M., Kebebew E., Kefford R. F., Kellis M., Kench J. G., Kennedy C. J., Kerssemakers J. N. A., Khoo D., Khoo V., Khuntikeo N., Khurana E., Kilpinen H., Kim H. K., Kim H. -L., Kim H. -Y., Kim H., Kim J., Kim J. K., Kim Y., King T. A., Klapper W., Kleinheinz K., Klimczak L. J., Knappskog S., Kneba M., Knoppers B. M., Koh Y., Komorowski J., Komura D., Komura M., Kong G., Kool M., Korbel J. O., Korchina V., Korshunov A., Koscher M., Koster R., Kote-Jarai Z., Koures A., Kovacevic M., Kremeyer B., Kretzmer H., Kreuz M., Krishnamurthy S., Kube D., Kumar K., Kumar P., Kumar S., Kumar Y., Kundra R., Kuppers R., Lagergren J., Lai P. H., Laird P. W., Lakhani S. R., Lalansingh C. M., Lalonde E., Lamaze F. C., Lambert A., Lander E., Landgraf P., Landoni L., Langerod A., Lanzos A., Larsimont D., Larsson E., Lathrop M., Lau L. M. S., Lawerenz C., Lawlor R. T., Lawrence M. S., Le X., Lee D., Lee E. A., Lee H. J., Lee J. J. -K., Lee J. -Y., Lee J., Lee M. T. M., Lee-Six H., Lehmann K. -V., Lehrach H., Lenze D., Leonard C. R., Leongamornlert D. A., Leshchiner I., Letourneau L., Letunic I., Levine D. A., Lewis L., Ley T., Li C., Li H. I., Li J., Li L., Li S., Li X., Li Y., Liang H., Liang S. -B., Lichter P., Lin P., Lin Z., Linehan W. M., Lingjaerde O. C., Liu D., Liu E. M., Liu F. -F., Liu F., Liu J., Liu X., Livingstone J., Livitz D., Livni N., Lochovsky L., Loeffler M., Long G. V., Lopez-Guillermo A., Lou S., Lovat L. B., Lu Y., Lu Y. -J., Luchini C., Lungu I., Luo X., Luxton H. J., Lynch A. G., Lype L., Lopez C., Lopez-Otin C., Ma E. Z., Ma Y., MacGrogan G., MacRae S., Macintyre G., Madsen T., Maejima K., Mafficini A., Maglinte D. T., Maitra A., Majumder P. P., Malcovati L., Malikic S., Malleo G., Mann G. J., Mantovani-Loffler L., Marchal K., Marchegiani G., Mardis E. R., Margolin A. A., Marin M. G., Markowetz F., Markowski J., Marks J., Marques-Bonet T., Marra M. A., Marsden L., Martens J. W. M., Martin-Subero J. I., Martincorena I., Martinez-Fundichely A., Maruvka Y. E., Mashl R. J., Massie C. E., Matthew T. J., Matthews L., Mayer E., Mayes S., Mayo M., Mbabaali F., McCune K., McDermott U., McGillivray P. D., McLellan M. D., McPherson J. D., McPherson J. R., McPherson T. A., Meier S. R., Meng A., Meng S., Menzies A., Merrett N. D., Merson S., Meyerson M., Meyerson W., Mieczkowski P. A., Mihaiescu G. L., Mijalkovic S., Mijalkovic-Lazic A. M., Mikkelsen T., Milella M., Mileshkin L., Miller C. A., Miller D. K., Miller J. K., Mills G. B., Milovanovic A., Minner S., Miotto M., Arnau G. M., Mirabello L., Mitchell C., Mitchell T. J., Miyano S., Miyoshi N., Mizuno S., Molnar-Gabor F., Moore M. J., Moore R. A., Morganella S., Morris Q. D., Morrison C., Mose L. E., Moser C. D., Muinos F., Mularoni L., Mungall A. J., Mungall K., Musgrove E. A., Mustonen V., Mutch D., Muyas F., Muzny D. M., Munoz A., Myers J., Myklebost O., Moller P., Nagae G., Nagrial A. M., Nakagama H., Nakagawa H., Nakamura H., Nakamura T., Nakano K., Nandi T., Nangalia J., Nastic M., Navarro A., Navarro F. C. P., Neal D. E., Nettekoven G., Newell F., Newhouse S. J., Newton Y., Ng A. W. T., Ng A., Nicholson J., Nicol D., Nie Y., Nielsen M. M., Noble M. S., Nones K., Northcott P. A., Notta F., O'Connor B. D., O'Donnell P., O'Donovan M., O'Meara S., O'Neill B. P., O'Neill J. R., Ocana D., Ochoa A., Oesper L., Ogden C., Ohdan H., Ohi K., Ohno-Machado L., Oien K. A., Ojesina A. I., Ojima H., Okusaka T., Ong C. K., Ossowski S., Ott G., Ouellette B. F. F., Paczkowska M., Paiella S., Pairojkul C., Pajic M., Pan-Hammarstrom Q., Papaemmanuil E., Papatheodorou I., Paramasivam N., Park J. W., Park J. -W., Park K., Park P. J., Parker J. S., Parsons S. L., Pass H., Pasternack D., Pastore A., Patch A. -M., Pauporte I., Pea A., Pearson J. V., Pedamallu C. S., Pedersen J. S., Pederzoli P., Peifer M., Pennell N. A., Perou C. M., Petersen G. M., Peto M., Petrelli N., Petryszak R., Pfister S. M., Phillips M., Pich O., Pickett H. A., Pihl T. D., Pillay N., Pinder S., Pinese M., Pinho A. V., Pitkanen E., Pivot X., Pineiro-Yanez E., Planko L., Plass C., Pons T., Popescu I., Potapova O., Prasad A., Preston S. R., Prinz M., Pritchard A. L., Provenzano E., Puente X. S., Puig S., Puiggros M., Pulido-Tamayo S., Pupo G. M., Purdie C. A., Quinn M. C., Rabionet R., Rader J. S., Radlwimmer B., Radovic P., Raeder B., Raine K. M., Ramakrishna M., Ramakrishnan K., Ramalingam S., Raphael B. J., Rathmell W. K., Rausch T., Reifenberger G., Reimand J., Reis-Filho J., Reuter V., Reyes-Salazar I., Reyna M. A., Reynolds S. M., Riazalhosseini Y., Richardson A. L., Richter J., Ringel M., Ringner M., Rino Y., Rippe K., Roach J., Roberts L. R., Roberts N. D., Roberts S. A., Robertson A. G., Robertson A. J., Rodriguez J. B., Rodriguez-Martin B., Rodriguez-Gonzalez F. G., Roehrl M. H. A., Rohde M., Rokutan H., Romieu G., Rooman I., Roques T., Rosebrock D., Rosenberg M., Rosenstiel P. C., Rosenwald A., Rowe E. W., Royo R., Rozen S. G., Rubanova Y., Rubio-Perez C., Rudneva V. A., Rusev B. C., Ruzzenente A., Ratsch G., Sabarinathan R., Sabelnykova V. Y., Sadeghi S., Sahinalp S. C., Saini N., Saito-Adachi M., Saksena G., Salcedo A., Salgado R., Salichos L., Sallari R., Saller C., Salvia R., Sam M., Samra J. S., Sanchez-Vega F., Sander C., Sanders G., Sarin R., Sarrafi I., Sasaki-Oku A., Sauer T., Sauter G., Saw R. P. M., Scardoni M., Scarlett C. J., Scarpa A., Scelo G., Schadendorf D., Schein J. E., Schilhabel M. B., Schlesner M., Schlomm T., Schmidt H. K., Schramm S. -J., Schreiber S., Schultz N., Schumacher S. E., Schwarz R. F., Scolyer R. A., Scott D., Scully R., Seethala R., Segre A. V., Selander I., Senbabaoglu Y., Sengupta S., Sereni E., Serra S., Shackleton M., Shah N. C., Shahabi S., Shang C. A., Shang P., Shapira O., Shelton T., Shen C., Shen H., Shepherd R., Shi R., Shi Y., Shiah Y. -J., Shih J., Shimizu E., Shimizu K., Shin S. J., Shiraishi Y., Shmaya T., Shmulevich I., Shorser S. I., Short C., Shrestha R., Shringarpure S. S., Shriver C., Shuai S., Sidiropoulos N., Sieuwerts A. M., Sieverling L., Signoretti S., Sikora K. O., Simbolo M., Simon R., Simons J. V., Simpson J. T., Simpson P. T., Singer S., Sinnott-Armstrong N., Sipahimalani P., Skelly T. J., Smid M., Smith-McCune K., Socci N. D., Sofia H. J., Soloway M. G., Song L., Sood A. K., Sothi S., Sotiriou C., Soulette C. M., Span P. N., Spellman P. T., Sperandio N., Spillane A. J., Spiro O., Spring J., Staaf J., Stadler P. F., Staib P., Stark S. G., Stebbings L., Stefansson O. A., Stegle O., Stenhouse A., Stewart C., Stilgenbauer S., Stratton M. R., Stretch J. R., Struck A. J., Stuart J. M., Stunnenberg H. G., Su H., Su X., Sungalee S., Susak H., Suzuki A., Sweep F., Szczepanowski M., Sultmann H., Yugawa T., Tam A., Tamborero D., Tan B. K. T., Tan D., Tan P., Tanaka H., Taniguchi H., Tanskanen T. J., Tarabichi M., Tarnuzzer R., Tarpey P., Taschuk M. L., Tatsuno K., Tavare S., Taylor D. F., Taylor-Weiner A., Teague J. W., Teh B. T., Tembe V., Temes J., Thayer S. P., Thiessen N., Thomas G., Thomas S., Thompson A., Thompson A. M., Thompson J. F., Thompson R. H., Thorne H., Thorne L. B., Thorogood A., Tiao G., Tijanic N., Timms L. E., Tirabosco R., Tojo M., Tommasi S., Toon C. W., Toprak U. H., Torrents D., Tortora G., Tost J., Totoki Y., Townend D., Traficante N., Treilleux I., Trotta J. -R., Trumper L. H. 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D., Williams A., Wilmott J. S., Wilson G. W., Wilson J. M., Wilson R. K., Winterhoff B., Wintersinger J. A., Wiznerowicz M., Wolf S., Wong B. H., Wong T., Wong W., Woo Y., Wood S., Wouters B. G., Wright A. J., Wright M. H., Wu D. -Y., Wu G., Wu J., Wu K., Wu Y., Wu Z., Xi L., Xia T., Xiang Q., Xiao X., Xing R., Xiong H., Xu Q., Xu Y., Xue H., Yachida S., Yakneen S., Yamaguchi R., Yamaguchi T. N., Yamamoto M., Yamamoto S., Yamaue H., Yang F., Yang H., Yang J. Y., Yang L., Yang S., Yang T. -P., Yang Y., Yao X., Yaspo M. -L., Yates L., Yau C., Ye C., Ye K., Yellapantula V. D., Yoon C. J., Yoon S. -S., Yu J., Yu K., Yu W., Yu Y., Yuan Y., Yuen D., Yung C. K., Zaikova O., Zamora J., Zapatka M., Zenklusen J. C., Zenz T., Zeps N., Zhang C. -Z., Zhang F., Zhang H., Zhang X., Zhang Y., Zhang Z., Zhao Z., Zheng L., Zheng X., Zhou W., Zhou Y., Zhu B., Zhu H., Zhu J., Zhu S., Zou L., Zou X., deFazio A., van As N., van Deurzen C. H. M., van de Vijver M. J., Veer L., von Mering C., Lauri Antti Aaltonen / Principal Investigator, Genome-Scale Biology (GSB) Research Program, Department of Medical and Clinical Genetics, Organismal and Evolutionary Biology Research Programme, Helsinki Institute for Information Technology, Institute of Biotechnology, Bioinformatics, Department of Computer Science, Faculty of Medicine, HUS Helsinki and Uusimaa Hospital District, University of St Andrews. Sir James Mackenzie Institute for Early Diagnosis, University of St Andrews. Cellular Medicine Division, University of St Andrews. Statistics, University of St Andrews. School of Medicine, Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Háskóli Íslands, University of Iceland, Li, C, Prokopec, S, Sun, R, Yousif, F, Schmitz, N, Al-Shahrour, F, Atwal, G, Bailey, P, Biankin, A, Boutros, P, Campbell, P, Chang, D, Cooke, S, Deshpande, V, Faltas, B, Faquin, W, Garraway, L, Getz, G, Grimmond, S, Haider, S, Hoadley, K, Jiao, W, Kaiser, V, Karlic, R, Kato, M, Kubler, K, Lazar, A, Louis, D, Margolin, A, Martin, S, Nahal-Bose, H, Nielsen, G, Nik-Zainal, S, Omberg, L, P'Ng, C, Perry, M, Polak, P, Rheinbay, E, Rubin, M, Semple, C, Sgroi, D, Shibata, T, Siebert, R, Smith, J, Stein, L, Stobbe, M, Thai, K, Wright, D, Wu, C, Yuan, K, Zhang, J, Aaltonen, L, Abascal, F, Abeshouse, A, Aburatani, H, Adams, D, Agrawal, N, Ahn, K, Ahn, S, Aikata, H, Akbani, R, Akdemir, K, Al-Ahmadie, H, Al-Sedairy, S, Alawi, M, Albert, M, Aldape, K, Alexandrov, L, Ally, A, Alsop, K, Alvarez, E, Amary, F, Amin, S, Aminou, B, Ammerpohl, O, Anderson, M, Ang, Y, Antonello, D, Anur, P, Aparicio, S, Appelbaum, E, Arai, Y, Aretz, A, Arihiro, K, Ariizumi, S, Armenia, J, Arnould, L, Asa, S, Assenov, Y, Aukema, S, Auman, J, Aure, M, Awadalla, P, Aymerich, M, Bader, G, Baez-Ortega, A, Bailey, M, Balasundaram, M, Balu, S, Bandopadhayay, P, Banks, R, Barbi, S, Barbour, A, Barenboim, J, Barnholtz-Sloan, J, Barr, H, Barrera, E, Bartlett, J, Bartolome, J, Bassi, C, Bathe, O, Baumhoer, D, Bavi, P, Baylin, S, Bazant, W, Beardsmore, D, Beck, T, Behjati, S, Behren, A, Niu, B, Bell, C, Beltran, S, Benz, C, Berchuck, A, Bergmann, A, Bergstrom, E, Berman, B, Berney, D, Bernhart, S, Beroukhim, R, Berrios, M, Bersani, S, Bertl, J, Betancourt, M, Bhandari, V, Bhosle, S, Bieg, M, Bigner, D, Binder, H, Birney, E, Birrer, M, Biswas, N, Bjerkehagen, B, Bodenheimer, T, Boice, L, Bonizzato, G, De Bono, J, Boot, A, Bootwalla, M, Borg, A, Borkhardt, A, Boroevich, K, Borozan, I, Borst, C, Bosenberg, M, Bosio, M, Boultwood, J, Bourque, G, Bova, G, Bowen, D, Bowlby, R, Bowtell, D, Boyault, S, Boyce, R, Boyd, J, Brazma, A, Brennan, P, Brewer, D, Brinkman, A, Bristow, R, Broaddus, R, Brock, J, Brock, M, Broeks, A, Brooks, A, Brooks, D, Brors, B, Brunak, S, Bruxner, T, Bruzos, A, Buchanan, A, Buchhalter, I, Buchholz, C, Bullman, S, Burke, H, Burkhardt, B, Burns, K, Busanovich, J, Bustamante, C, Butler, A, Butte, A, Byrne, N, Borresen-Dale, A, Caesar-Johnson, S, Cafferkey, A, Cahill, D, Calabrese, C, Caldas, C, Calvo, F, Camacho, N, Campo, E, Cantu, C, Cao, S, Carey, T, Carlevaro-Fita, J, Carlsen, R, Cataldo, I, Cazzola, M, Cebon, J, Cerfolio, R, Chadwick, D, Chakravarty, D, Chalmers, D, Chan, C, Chan, K, Chan-Seng-Yue, M, Chandan, V, Chanock, S, Chantrill, L, Chateigner, A, Chatterjee, N, Chayama, K, Chen, H, Chen, J, Chen, K, Chen, Y, Chen, Z, Cherniack, A, Chien, J, Chiew, Y, Chin, S, Cho, J, Cho, S, Choi, J, Choi, W, Chomienne, C, Chong, Z, Choo, S, Chou, A, Christ, A, Christie, E, Chuah, E, Cibulskis, C, Cibulskis, K, Cingarlini, S, Clapham, P, Claviez, A, Cleary, S, Cloonan, N, Cmero, M, Collins, C, Connor, A, Cooper, C, Cope, L, Corbo, V, Cordes, M, Cordner, S, Cortes-Ciriano, I, Covington, K, Cowin, P, Craft, B, Craft, D, Creighton, C, Cun, Y, Curley, E, Cutcutache, I, Czajka, K, Czerniak, B, Dagg, R, Danilova, L, Davi, M, Davidson, N, Davies, H, Davis, I, Davis-Dusenbery, B, Dawson, K, De La Vega, F, De Paoli-Iseppi, R, Defreitas, T, Dei Tos, A, Delaneau, O, Demchok, J, Demeulemeester, J, Demidov, G, Demircioglu, D, Dennis, N, Denroche, R, Dentro, S, Desai, N, Deshwar, A, Desmedt, C, Deu-Pons, J, Dhalla, N, Dhani, N, Dhingra, P, Dhir, R, Dibiase, A, Diamanti, K, Ding, L, Ding, S, Dinh, H, Dirix, L, Doddapaneni, H, Donmez, N, Dow, M, Drapkin, R, Drechsel, O, Drews, R, Serge, S, Dudderidge, T, Dueso-Barroso, A, Dunford, A, Dunn, M, Dursi, L, Duthie, F, Dutton-Regester, K, Eagles, J, Easton, D, Edmonds, S, Edwards, P, Edwards, S, Eeles, R, Ehinger, A, Eils, J, Eils, R, El-Naggar, A, Eldridge, M, Ellrott, K, Erkek, S, Escaramis, G, Espiritu, S, Estivill, X, Etemadmoghadam, D, Eyfjord, J, Fan, D, Fan, Y, Farcas, C, Fassan, M, Fatima, A, Favero, F, Fayzullaev, N, Felau, I, Fereday, S, Ferguson, M, Ferretti, V, Feuerbach, L, Field, M, Fink, J, Finocchiaro, G, Fisher, C, Fittall, M, Fitzgerald, A, Fitzgerald, R, Flanagan, A, Fleshner, N, Flicek, P, Foekens, J, Fong, K, Fonseca, N, Foster, C, Fox, N, Fraser, M, Frazer, S, Frenkel-Morgenstern, M, Friedman, W, Frigola, J, Fronick, C, Fujimoto, A, Fujita, M, Fukayama, M, Fulton, L, Fulton, R, Furuta, M, Futreal, P, Fullgrabe, A, Gabriel, S, Gallinger, S, Gambacorti Passerini, C, Gao, J, Gao, S, Garred, O, Garrison, E, Garsed, D, Gehlenborg, N, Gelpi, J, George, J, Gerhard, D, Gerhauser, C, Gershenwald, J, Gerstein, M, Gerstung, M, Ghori, M, Ghossein, R, Giama, N, Gibbs, R, Gill, A, Gill, P, Giri, D, Glodzik, D, Gnanapragasam, V, Goebler, M, Goldman, M, Gomez, C, Gonzalez, S, Gonzalez-Perez, A, Gordenin, D, Gossage, J, Gotoh, K, Govindan, R, Grabau, D, Graham, J, Grant, R, Green, A, Green, E, Greger, L, Grehan, N, Grimaldi, S, Grossman, R, Grundhoff, A, Gundem, G, Guo, Q, Gupta, M, Gupta, S, Gut, I, Gut, M, Goke, J, Ha, G, Haake, A, Haan, D, Haas, S, Haase, K, Haber, J, Habermann, N, Hach, F, Hama, N, Hamdy, F, Hamilton, A, Hamilton, M, Han, L, Hanna, G, Hansmann, M, Haradhvala, N, Harismendy, O, Harliwong, I, Harmanci, A, Harrington, E, Hasegawa, T, Haussler, D, Hawkins, S, Hayami, S, Hayashi, S, Hayes, D, Hayes, S, Hayward, N, Hazell, S, He, Y, Heath, A, Heath, S, Hedley, D, Hegde, A, Heiman, D, Heinold, M, Heins, Z, Heisler, L, Hellstrom-Lindberg, E, Helmy, M, Heo, S, Hepperla, A, Heredia-Genestar, J, Herrmann, C, Hersey, P, Hess, J, Hilmarsdottir, H, Hinton, J, Hirano, S, Hiraoka, N, Hobolth, A, Hodzic, E, Hoell, J, Hoffmann, S, Hofmann, O, Holbrook, A, Holik, A, Hollingsworth, M, Holmes, O, Holt, R, Hong, C, Hong, E, Hong, J, Hooijer, G, Hornshoj, H, Hosoda, F, Hou, Y, Hovestadt, V, Howat, W, Hoyle, A, Hruban, R, Hu, J, Hu, T, Hua, X, Huang, K, Huang, M, Huang, V, Huang, Y, Huber, W, Hudson, T, Hummel, M, Hung, J, Huntsman, D, Hupp, T, Huse, J, Huska, M, Hutter, B, Hutter, C, Hubschmann, D, Iacobuzio-Donahue, C, Imbusch, C, Imielinski, M, Imoto, S, Isaacs, W, Isaev, K, Ishikawa, S, Iskar, M, Islam, S, Ittmann, M, Ivkovic, S, Izarzugaza, J, Jacquemier, J, Jakrot, V, Jamieson, N, Jang, G, Jang, S, Jayaseelan, J, Jayasinghe, R, Jefferys, S, Jegalian, K, Jennings, J, Jeon, S, Jerman, L, Ji, Y, Johansson, P, Johns, A, Johns, J, Johnson, R, Johnson, T, Jolly, C, Joly, Y, Jonasson, J, Jones, C, Jones, D, Jones, N, Jones, S, Jonkers, J, Ju, Y, Juhl, H, Jung, J, Juul, M, Juul, R, Juul, S, Jager, N, Kabbe, R, Kahles, A, Kahraman, A, Kakavand, H, Kalimuthu, S, von Kalle, C, Kang, K, Karaszi, K, Karlan, B, Karsch, D, Kasaian, K, Kassahn, K, Katai, H, Katoh, H, Kawakami, Y, Kay, J, Kazakoff, S, Kazanov, M, Keays, M, Kebebew, E, Kefford, R, Kellis, M, Kench, J, Kennedy, C, Kerssemakers, J, Khoo, D, Khoo, V, Khuntikeo, N, Khurana, E, Kilpinen, H, Kim, H, Kim, J, Kim, Y, King, T, Klapper, W, Kleinheinz, K, Klimczak, L, Knappskog, S, Kneba, M, Knoppers, B, Koh, Y, Komorowski, J, Komura, D, Komura, M, Kong, G, Kool, M, Korbel, J, Korchina, V, Korshunov, A, Koscher, M, Koster, R, Kote-Jarai, Z, Koures, A, Kovacevic, M, Kremeyer, B, Kretzmer, H, Kreuz, M, Krishnamurthy, S, Kube, D, Kumar, K, Kumar, P, Kumar, S, Kumar, Y, Kundra, R, Kuppers, R, Lagergren, J, Lai, P, Laird, P, Lakhani, S, Lalansingh, C, Lalonde, E, Lamaze, F, Lambert, A, Lander, E, Landgraf, P, Landoni, L, Langerod, A, Lanzos, A, Larsimont, D, Larsson, E, Lathrop, M, Lau, L, Lawerenz, C, Lawlor, R, Lawrence, M, Le, X, Lee, D, Lee, E, Lee, H, Lee, J, Lee, M, Lee-Six, H, Lehmann, K, Lehrach, H, Lenze, D, Leonard, C, Leongamornlert, D, Leshchiner, I, Letourneau, L, Letunic, I, Levine, D, Lewis, L, Ley, T, Li, H, Li, J, Li, L, Li, S, Li, X, Li, Y, Liang, H, Liang, S, Lichter, P, Lin, P, Lin, Z, Linehan, W, Lingjaerde, O, Liu, D, Liu, E, Liu, F, Liu, J, Liu, X, Livingstone, J, Livitz, D, Livni, N, Lochovsky, L, Loeffler, M, Long, G, Lopez-Guillermo, A, Lou, S, Lovat, L, Lu, Y, Luchini, C, Lungu, I, Luo, X, Luxton, H, Lynch, A, Lype, L, Lopez, C, Lopez-Otin, C, Ma, E, Ma, Y, Macgrogan, G, Macrae, S, Macintyre, G, Madsen, T, Maejima, K, Mafficini, A, Maglinte, D, Maitra, A, Majumder, P, Malcovati, L, Malikic, S, Malleo, G, Mann, G, Mantovani-Loffler, L, Marchal, K, Marchegiani, G, Mardis, E, Marin, M, Markowetz, F, Markowski, J, Marks, J, Marques-Bonet, T, Marra, M, Marsden, L, Martens, J, Martin-Subero, J, Martincorena, I, Martinez-Fundichely, A, Maruvka, Y, Mashl, R, Massie, C, Matthew, T, Matthews, L, Mayer, E, Mayes, S, Mayo, M, Mbabaali, F, Mccune, K, Mcdermott, U, Mcgillivray, P, Mclellan, M, Mcpherson, J, Mcpherson, T, Meier, S, Meng, A, Meng, S, Menzies, A, Merrett, N, Merson, S, Meyerson, M, Meyerson, W, Mieczkowski, P, Mihaiescu, G, Mijalkovic, S, Mijalkovic-Lazic, A, Mikkelsen, T, Milella, M, Mileshkin, L, Miller, C, Miller, D, Miller, J, Mills, G, Milovanovic, A, Minner, S, Miotto, M, Arnau, G, Mirabello, L, Mitchell, C, Mitchell, T, Miyano, S, Miyoshi, N, Mizuno, S, Molnar-Gabor, F, Moore, M, Moore, R, Morganella, S, Morris, Q, Morrison, C, Mose, L, Moser, C, Muinos, F, Mularoni, L, Mungall, A, Mungall, K, Musgrove, E, Mustonen, V, Mutch, D, Muyas, F, Muzny, D, Munoz, A, Myers, J, Myklebost, O, Moller, P, Nagae, G, Nagrial, A, Nakagama, H, Nakagawa, H, Nakamura, H, Nakamura, T, Nakano, K, Nandi, T, Nangalia, J, Nastic, M, Navarro, A, Navarro, F, Neal, D, Nettekoven, G, Newell, F, Newhouse, S, Newton, Y, Ng, A, Nicholson, J, Nicol, D, Nie, Y, Nielsen, M, Noble, M, Nones, K, Northcott, P, Notta, F, O'Connor, B, O'Donnell, P, O'Donovan, M, O'Meara, S, O'Neill, B, O'Neill, J, Ocana, D, Ochoa, A, Oesper, L, Ogden, C, Ohdan, H, Ohi, K, Ohno-Machado, L, Oien, K, Ojesina, A, Ojima, H, Okusaka, T, Ong, C, Ossowski, S, Ott, G, Ouellette, B, Paczkowska, M, Paiella, S, Pairojkul, C, Pajic, M, Pan-Hammarstrom, Q, Papaemmanuil, E, Papatheodorou, I, Paramasivam, N, Park, J, Park, K, Park, P, Parker, J, Parsons, S, Pass, H, Pasternack, D, Pastore, A, Patch, A, Pauporte, I, Pea, A, Pearson, J, Pedamallu, C, Pedersen, J, Pederzoli, P, Peifer, M, Pennell, N, Perou, C, Petersen, G, Peto, M, Petrelli, N, Petryszak, R, Pfister, S, Phillips, M, Pich, O, Pickett, H, Pihl, T, Pillay, N, Pinder, S, Pinese, M, Pinho, A, Pitkanen, E, Pivot, X, Pineiro-Yanez, E, Planko, L, Plass, C, Pons, T, Popescu, I, Potapova, O, Prasad, A, Preston, S, Prinz, M, Pritchard, A, Provenzano, E, Puente, X, Puig, S, Puiggros, M, Pulido-Tamayo, S, Pupo, G, Purdie, C, Quinn, M, Rabionet, R, Rader, J, Radlwimmer, B, Radovic, P, Raeder, B, Raine, K, Ramakrishna, M, Ramakrishnan, K, Ramalingam, S, Raphael, B, Rathmell, W, Rausch, T, Reifenberger, G, Reimand, J, Reis-Filho, J, Reuter, V, Reyes-Salazar, I, Reyna, M, Reynolds, S, Riazalhosseini, Y, Richardson, A, Richter, J, Ringel, M, Ringner, M, Rino, Y, Rippe, K, Roach, J, Roberts, L, Roberts, N, Roberts, S, Robertson, A, Rodriguez, J, Rodriguez-Martin, B, Rodriguez-Gonzalez, F, Roehrl, M, Rohde, M, Rokutan, H, Romieu, G, Rooman, I, Roques, T, Rosebrock, D, Rosenberg, M, Rosenstiel, P, Rosenwald, A, Rowe, E, Royo, R, Rozen, S, Rubanova, Y, Rubio-Perez, C, Rudneva, V, Rusev, B, Ruzzenente, A, Ratsch, G, Sabarinathan, R, Sabelnykova, V, Sadeghi, S, Sahinalp, S, Saini, N, Saito-Adachi, M, Saksena, G, Salcedo, A, Salgado, R, Salichos, L, Sallari, R, Saller, C, Salvia, R, Sam, M, Samra, J, Sanchez-Vega, F, Sander, C, Sanders, G, Sarin, R, Sarrafi, I, Sasaki-Oku, A, Sauer, T, Sauter, G, Saw, R, Scardoni, M, Scarlett, C, Scarpa, A, Scelo, G, Schadendorf, D, Schein, J, Schilhabel, M, Schlesner, M, Schlomm, T, Schmidt, H, Schramm, S, Schreiber, S, Schultz, N, Schumacher, S, Schwarz, R, Scolyer, R, Scott, D, Scully, R, Seethala, R, Segre, A, Selander, I, Senbabaoglu, Y, Sengupta, S, Sereni, E, Serra, S, Shackleton, M, Shah, N, Shahabi, S, Shang, C, Shang, P, Shapira, O, Shelton, T, Shen, C, Shen, H, Shepherd, R, Shi, R, Shi, Y, Shiah, Y, Shih, J, Shimizu, E, Shimizu, K, Shin, S, Shiraishi, Y, Shmaya, T, Shmulevich, I, Shorser, S, Short, C, Shrestha, R, Shringarpure, S, Shriver, C, Shuai, S, Sidiropoulos, N, Sieuwerts, A, Sieverling, L, Signoretti, S, Sikora, K, Simbolo, M, Simon, R, Simons, J, Simpson, J, Simpson, P, Singer, S, Sinnott-Armstrong, N, Sipahimalani, P, Skelly, T, Smid, M, Smith-McCune, K, Socci, N, Sofia, H, Soloway, M, Song, L, Sood, A, Sothi, S, Sotiriou, C, Soulette, C, Span, P, Spellman, P, Sperandio, N, Spillane, A, Spiro, O, Spring, J, Staaf, J, Stadler, P, Staib, P, Stark, S, Stebbings, L, Stefansson, O, Stegle, O, Stenhouse, A, Stewart, C, Stilgenbauer, S, Stratton, M, Stretch, J, Struck, A, Stuart, J, Stunnenberg, H, Su, H, Su, X, Sungalee, S, Susak, H, Suzuki, A, Sweep, F, Szczepanowski, M, Sultmann, H, Yugawa, T, Tam, A, Tamborero, D, Tan, B, Tan, D, Tan, P, Tanaka, H, Taniguchi, H, Tanskanen, T, Tarabichi, M, Tarnuzzer, R, Tarpey, P, Taschuk, M, Tatsuno, K, Tavare, S, Taylor, D, Taylor-Weiner, A, Teague, J, Teh, B, Tembe, V, Temes, J, Thayer, S, Thiessen, N, Thomas, G, Thomas, S, Thompson, A, Thompson, J, Thompson, R, Thorne, H, Thorne, L, Thorogood, A, Tiao, G, Tijanic, N, Timms, L, Tirabosco, R, Tojo, M, Tommasi, S, Toon, C, Toprak, U, Torrents, D, Tortora, G, Tost, J, Totoki, Y, Townend, D, Traficante, N, Treilleux, I, Trotta, J, Trumper, L, Tsao, M, Tsunoda, T, Tubio, J, Tucker, O, Turkington, R, Turner, D, Tutt, A, Ueno, M, Ueno, N, Umbricht, C, Umer, H, Underwood, T, Urban, L, Urushidate, T, Ushiku, T, Uuskula-Reimand, L, Valencia, A, Van Den Berg, D, Van Laere, S, Van Loo, P, Van Meir, E, Van den Eynden, G, Van der Kwast, T, Vasudev, N, Vazquez, M, Vedururu, R, Veluvolu, U, Vembu, S, Verbeke, L, Vermeulen, P, Verrill, C, Viari, A, Vicente, D, Vicentini, C, Raghavan, K, Viksna, J, Vilain, R, Villasante, I, Vincent-Salomon, A, Visakorpi, T, Voet, D, Vyas, P, Vazquez-Garcia, I, Waddell, N, Wadelius, 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C, Zhang, F, Zhang, H, Zhang, X, Zhang, Y, Zhang, Z, Zhao, Z, Zheng, L, Zheng, X, Zhou, W, Zhou, Y, Zhu, B, Zhu, H, Zhu, J, Zhu, S, Zou, L, Zou, X, Defazio, A, van As, N, van Deurzen, C, van de Vijver, M, Veer, L, von Mering, C, Natural Sciences and Engineering Research Council of Canada, Canadian Institutes of Health Research, Genome Canada, Canada Foundation for Innovation, National Institutes of Health (US), National Cancer Institute (US), Pathology, CCA - Cancer biology and immunology, Graduate School, Laboratory Genetic Metabolic Diseases, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, CCA -Cancer Center Amsterdam, Li, Constance H. [0000-0002-5487-7225], Prokopec, Stephenie D. [0000-0001-7936-8577], Boutros, Paul C. [0000-0003-0553-7520], Apollo - University of Cambridge Repository, Tampere University, BioMediTech, TAYS Cancer Centre, Basic (bio-) Medical Sciences, Li, Constance H [0000-0002-5487-7225], Prokopec, Stephenie D [0000-0001-7936-8577], Boutros, Paul C [0000-0003-0553-7520], and Medical Oncology
- Subjects
sex differences ,Male ,Colorectal cancer ,Kynferði ,02 engineering and technology ,0302 clinical medicine ,DISPARITIES ,Epidemiology of cancer ,Cancer genomics ,lcsh:Science ,Càncer ,Cancer genetics, Genome informatics, Cancer genomics, Oncogenes ,Cancer genetics ,Exome ,Cancer ,0303 health sciences ,Mutation ,Neoplasms -- genetics ,1184 Genetics, developmental biology, physiology ,Neoplasms/genetics ,3. Good health ,030220 oncology & carcinogenesis ,Medical genetics ,0210 nano-technology ,Human ,Sex characteristics ,medicine.medical_specialty ,Science ,Genomic Instability ,General Biochemistry, Genetics and Molecular Biology ,RC0254 ,Càncer -- Epidemiologia ,Open Reading Frames ,03 medical and health sciences ,SDG 3 - Good Health and Well-being ,Chromosomal Instability ,Sex differences ,Genetics ,Humans ,beta Catenin -- genetics ,Sex organ ,SIGNATURES ,45 ,RC0254 Neoplasms. Tumors. Oncology (including Cancer) ,Oncogenes ,medicine.disease ,692/4028/67/69 ,Cancérologie ,Genòmica ,Logistic Models ,030104 developmental biology ,lcsh:Q ,PCAWG Tumour Subtypes and Clinical Translation ,Human genome ,119 ,0301 basic medicine ,Medizin ,General Physics and Astronomy ,medicine.disease_cause ,Bioinformatics ,Genome informatics ,Genome ,Neoplasms ,38/23 ,Medicine and Health Sciences ,Body Size ,beta Catenin ,Sex Characteristics ,318 Medical biotechnology ,Women's cancers Radboud Institute for Molecular Life Sciences [Radboudumc 17] ,Multidisciplinary ,article ,3rd-DAS ,021001 nanoscience & nanotechnology ,humanities ,Women's cancers Radboud Institute for Health Sciences [Radboudumc 17] ,Causality ,oncology ,1181 Ecology, evolutionary biology ,SURVIVAL ,631/114/2785 ,Female ,Càncer -- Tractament ,Oncogenes -- genetics ,beta Catenin/genetics ,3122 Cancers ,610 Medicine & health ,QH426 Genetics ,Biology ,Cancer epidemiology ,Rare Diseases ,631/67/68 ,Krabbameinsrannsóknir ,medicine ,ddc:610 ,Gene ,QH426 ,030304 developmental biology ,Krabbamein ,Oncogenes/genetics ,Genome, Human ,Sex organs ,Human Genome ,PCAWG Consortium ,General Chemistry ,GENE ,Good Health and Well Being ,Estudis de gènere ,oncogenic mutational processes ,692/4028/67/395 ,Diferències entre sexes ,Gender studies ,3111 Biomedicine - Abstract
Publisher's version (útgefin grein), Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research., We thank all the members of the Boutros lab for insightful discussions. This study was conducted with the support of the Ontario Institute for Cancer Research to P.C.B. through funding provided by the Government of Ontario. This work was supported by the Discovery Frontiers: Advancing Big Data Science in Genomics Research program, which is jointly funded by the Natural Sciences and Engineering Research Council (NSERC) of Canada, the Canadian Institutes of Health Research (CIHR), Genome Canada and the Canada Foundation for Innovation (CFI). P.C.B. was supported by a Terry Fox Research Institute New Investigator Award and a CIHR New Investigator Award. This work was supported by an NSERC Discovery grant and by Canadian Institutes of Health Research, grant #SVB-145586, to P.C.B. This work was supported by the NIH/NCI under award number P30CA016042 and an operating grant from the National Cancer Institute Early Detection Research Network (1U01CA214194-01). We acknowledge the contributions of the many clinical networks across ICGC and TCGA who provided samples and data to the PCAWG Consortium, and the contributions of the Technical Working Group and the Germline Working Group of the PCAWG Consortium for collation, realignment and harmonised variant calling of the cancer genomes used in this study. We thank the patients and their families for their participation in the individual ICGC and TCGA projects.
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- 2020
5. Analyses of non-coding somatic drivers in 2,658 cancer whole genomes
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Rheinbay E., Nielsen M. M., Abascal F., Wala J. A., Shapira O., Tiao G., Hornshoj H., Hess J. M., Juul R. I., Lin Z., Feuerbach L., Sabarinathan R., Madsen T., Kim J., Mularoni L., Shuai S., Lanzos A., Herrmann C., Maruvka Y. E., Shen C., Amin S. B., Bandopadhayay P., Bertl J., Boroevich K. A., Busanovich J., Carlevaro-Fita J., Chakravarty D., Chan C. W. Y., Craft D., Dhingra P., Diamanti K., Fonseca N. A., Gonzalez-Perez A., Guo Q., Hamilton M. P., Haradhvala N. J., Hong C., Isaev K., Johnson T. A., Juul M., Kahles A., Kahraman A., Kim Y., Komorowski J., Kumar K., Kumar S., Lee D., Lehmann K. -V., Li Y., Liu E. M., Lochovsky L., Park K., Pich O., Roberts N. D., Saksena G., Schumacher S. E., Sidiropoulos N., Sieverling L., Sinnott-Armstrong N., Stewart C., Tamborero D., Tubio J. M. C., Umer H. M., Uuskula-Reimand L., Wadelius C., Wadi L., Yao X., Zhang C. -Z., Zhang J., Haber J. E., Hobolth A., Imielinski M., Kellis M., Lawrence M. S., von Mering C., Nakagawa H., Raphael B. J., Rubin M. A., Sander C., Stein L. D., Stuart J. M., Tsunoda T., Wheeler D. A., Johnson R., Reimand J., Gerstein M., Khurana E., Campbell P. J., Lopez-Bigas N., Bader G. D., Barenboim J., Beroukhim R., Brunak S., Chen K., Choi J. K., Deu-Pons J., Fink J. L., Frigola J., Gambacorti Passerini C., Garsed D. W., Getz G., Gut I. G., Haan D., Harmanci A. O., Helmy M., Hodzic E., Izarzugaza J. M. G., Kim J. K., Korbel J. O., Larsson E., Li S., Li X., Lou S., Marchal K., Martincorena I., Martinez-Fundichely A., McGillivray P. D., Meyerson W., Muinos F., Paczkowska M., Pedersen J. S., Pons T., Pulido-Tamayo S., Reyes-Salazar I., Reyna M. A., Rubio-Perez C., Sahinalp S. C., Salichos L., Shackleton M., Shrestha R., Valencia A., Vazquez M., Verbeke L. P. C., Wang J., Warrell J., Waszak S. M., Weischenfeldt J., Wu G., Yu J., Zhang X., Zhang Y., Zhao Z., Zou L., Akdemir K. C., Alvarez E. G., Baez-Ortega A., Boutros P. C., Bowtell D. D. L., Brors B., Burns K. H., Chan K., Cortes-Ciriano I., Dueso-Barroso A., Dunford A. J., Edwards P. A., Estivill X., Etemadmoghadam D., Frenkel-Morgenstern M., Gordenin D. A., Hutter B., Jones D. T. W., Ju Y. S., Kazanov M. D., Klimczak L. J., Koh Y., Lee E. A., Lee J. J. -K., Lynch A. G., Macintyre G., Markowetz F., Meyerson M., Miyano S., Navarro F. C. P., Ossowski S., Park P. J., Pearson J. V., Puiggros M., Rippe K., Roberts S. A., Rodriguez-Martin B., Scully R., Torrents D., Villasante I., Waddell N., Yang L., Yoon S. -S., Zamora J., Rheinbay, E, Nielsen, M, Abascal, F, Wala, J, Shapira, O, Tiao, G, Hornshoj, H, Hess, J, Juul, R, Lin, Z, Feuerbach, L, Sabarinathan, R, Madsen, T, Kim, J, Mularoni, L, Shuai, S, Lanzos, A, Herrmann, C, Maruvka, Y, Shen, C, Amin, S, Bandopadhayay, P, Bertl, J, Boroevich, K, Busanovich, J, Carlevaro-Fita, J, Chakravarty, D, Chan, C, Craft, D, Dhingra, P, Diamanti, K, Fonseca, N, Gonzalez-Perez, A, Guo, Q, Hamilton, M, Haradhvala, N, Hong, C, Isaev, K, Johnson, T, Juul, M, Kahles, A, Kahraman, A, Kim, Y, Komorowski, J, Kumar, K, Kumar, S, Lee, D, Lehmann, K, Li, Y, Liu, E, Lochovsky, L, Park, K, Pich, O, Roberts, N, Saksena, G, Schumacher, S, Sidiropoulos, N, Sieverling, L, Sinnott-Armstrong, N, Stewart, C, Tamborero, D, Tubio, J, Umer, H, Uuskula-Reimand, L, Wadelius, C, Wadi, L, Yao, X, Zhang, C, Zhang, J, Haber, J, Hobolth, A, Imielinski, M, Kellis, M, Lawrence, M, von Mering, C, Nakagawa, H, Raphael, B, Rubin, M, Sander, C, Stein, L, Stuart, J, Tsunoda, T, Wheeler, D, Johnson, R, Reimand, J, Gerstein, M, Khurana, E, Campbell, P, Lopez-Bigas, N, Bader, G, Barenboim, J, Beroukhim, R, Brunak, S, Chen, K, Choi, J, Deu-Pons, J, Fink, J, Frigola, J, Gambacorti Passerini, C, Garsed, D, Getz, G, Gut, I, Haan, D, Harmanci, A, Helmy, M, Hodzic, E, Izarzugaza, J, Korbel, J, Larsson, E, Li, S, Li, X, Lou, S, Marchal, K, Martincorena, I, Martinez-Fundichely, A, Mcgillivray, P, Meyerson, W, Muinos, F, Paczkowska, M, Pedersen, J, Pons, T, Pulido-Tamayo, S, Reyes-Salazar, I, Reyna, M, Rubio-Perez, C, Sahinalp, S, Salichos, L, Shackleton, M, Shrestha, R, Valencia, A, Vazquez, M, Verbeke, L, Wang, J, Warrell, J, Waszak, S, Weischenfeldt, J, Wu, G, Yu, J, Zhang, X, Zhang, Y, Zhao, Z, Zou, L, Akdemir, K, Alvarez, E, Baez-Ortega, A, Boutros, P, Bowtell, D, Brors, B, Burns, K, Chan, K, Cortes-Ciriano, I, Dueso-Barroso, A, Dunford, A, Edwards, P, Estivill, X, Etemadmoghadam, D, Frenkel-Morgenstern, M, Gordenin, D, Hutter, B, Jones, D, Ju, Y, Kazanov, M, Klimczak, L, Koh, Y, Lee, E, Lee, J, Lynch, A, Macintyre, G, Markowetz, F, Meyerson, M, Miyano, S, Navarro, F, Ossowski, S, Park, P, Pearson, J, Puiggros, M, Rippe, K, Roberts, S, Rodriguez-Martin, B, Scully, R, Torrents, D, Villasante, I, Waddell, N, Yang, L, Yoon, S, Zamora, J, Gonzalez-Perez, Abel [0000-0002-8582-4660], Apollo - University of Cambridge Repository, University of St Andrews. School of Medicine, University of St Andrews. Statistics, University of St Andrews. Sir James Mackenzie Institute for Early Diagnosis, and University of St Andrews. Cellular Medicine Division
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QA75 ,EXPRESSION ,SELECTION ,Untranslated region ,medicine.medical_specialty ,GENES ,QA75 Electronic computers. Computer science ,610 Medicine & health ,Genome-wide association study ,Tumors -- Genètica ,Computational biology ,Biology ,Genoma humà ,ANNOTATION ,Genome ,Article ,RC0254 ,03 medical and health sciences ,0302 clinical medicine ,SDG 3 - Good Health and Well-being ,REGULATORY MUTATIONS ,Cancer genomics ,Medicine and Health Sciences ,medicine ,RECURRENT ,Gene ,030304 developmental biology ,Medicinsk genetik ,0303 health sciences ,Women's cancers Radboud Institute for Molecular Life Sciences [Radboudumc 17] ,Multidisciplinary ,LANDSCAPE ,RC0254 Neoplasms. Tumors. Oncology (including Cancer) ,Point mutation ,Mutació (Biologia) ,Biology and Life Sciences ,Cancer genomics, Computational biology, bioinformatics, protein-coding genes, cancer, non-coding ,3rd-DAS ,Human genetics ,Women's cancers Radboud Institute for Health Sciences [Radboudumc 17] ,Computational biology and bioinformatics ,3. Good health ,TERT PROMOTER MUTATIONS ,TARGET ,DISCOVERY ,Medical genetics ,Human genome ,Medical Genetics ,030217 neurology & neurosurgery - Abstract
The discovery of drivers of cancer has traditionally focused on protein-coding genes1–4. Here we present analyses of driver point mutations and structural variants in non-coding regions across 2,658 genomes from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium5 of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). For point mutations, we developed a statistically rigorous strategy for combining significance levels from multiple methods of driver discovery that overcomes the limitations of individual methods. For structural variants, we present two methods of driver discovery, and identify regions that are significantly affected by recurrent breakpoints and recurrent somatic juxtapositions. Our analyses confirm previously reported drivers6,7, raise doubts about others and identify novel candidates, including point mutations in the 5′ region of TP53, in the 3′ untranslated regions of NFKBIZ and TOB1, focal deletions in BRD4 and rearrangements in the loci of AKR1C genes. We show that although point mutations and structural variants that drive cancer are less frequent in non-coding genes and regulatory sequences than in protein-coding genes, additional examples of these drivers will be found as more cancer genomes become available., Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.
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- 2020
6. Pan-cancer analysis of whole genomes identifies driver rearrangements promoted by LINE-1 retrotransposition
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Rodriguez-Martin, B., Alvarez, E.G., Baez-Ortega, A., Zamora, J., Supek, F., Demeulemeester, J., Santamarina, M., Ju, Y.S., Temes, J., Garcia-Souto, D., Detering, H., Li, Y., Rodriguez-Castro, J., Dueso-Barroso, A., Bruzos, A.L., Dentro, S.C., Blanco, M.G., Contino, G., Ardeljan, D., Tojo, M., Roberts, N.D., Zumalave, S., Edwards, P.A., Weischenfeldt, J., Puiggròs, M., Chong, Z., Chen, K., Lee, E.A., Wala, J.A., Raine, K., Butler, A., Waszak, S.M., Navarro, F.C.P., Schumacher, S.E., Monlong, J., Maura, F., Bolli, N., Bourque, G., Gerstein, M., Park, P.J., Wedge, D.C., Beroukhim, R., Torrents, D., Korbel, J.O., Martincorena, I., Fitzgerald, R.C., Van Loo, P., Kazazian, H.H., Burns, K.H., Akdemir, K.C., Boutros, P.C., Bowtell, D.D.L., Brors, B., Campbell, P.J., Chan, K., Cortés-Ciriano, I., Dunford, A.J., Estivill, X., Etemadmoghadam, D., Feuerbach, L., Fink, J.L., Frenkel-Morgenstern, M., Garsed, D.W., Gordenin, D.A., Haan, D., Haber, J.E., Hess, J.M., Hutter, B., Imielinski, M., Jones, D.T.W., Kazanov, M.D., Klimczak, L.J., Koh, Y., Kumar, K., Lee, J.J.-K., Lynch, A.G., Macintyre, G., Markowetz, F., Martinez-Fundichely, A., Meyerson, M., Miyano, S., Nakagawa, H., Ossowski, S., Pearson, J.V., Rippe, K., Roberts, S.A., Scully, R., Shackleton, M., Sidiropoulos, N., Sieverling, L., Stewart, C., Tubio, J.M.C., Villasante, I., Waddell, N., Yang, L., Yao, X., Yoon, S.-S., Zhang, C.-Z., University of St Andrews. School of Medicine, University of St Andrews. Statistics, University of St Andrews. Sir James Mackenzie Institute for Early Diagnosis, and University of St Andrews. Cellular Medicine Division
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Somatic cell ,Carcinogenesis ,QH301 Biology ,Retrotransposon ,medicine.disease_cause ,Genoma humà ,Genome ,0302 clinical medicine ,Neoplasms ,ELEMENTS ,Carcinogènesi ,Cancer ,Genetics ,Gene Rearrangement ,Genetics & Heredity ,0303 health sciences ,Women's cancers Radboud Institute for Molecular Life Sciences [Radboudumc 17] ,Manchester Cancer Research Centre ,3rd-DAS ,Genomics ,Neoplasms/genetics ,SOMATIC RETROTRANSPOSITION ,Women's cancers Radboud Institute for Health Sciences [Radboudumc 17] ,3. Good health ,READ ALIGNMENT ,030220 oncology & carcinogenesis ,Retroelements/genetics ,Life Sciences & Biomedicine ,Retroelements ,INSTABILITY ,L1 RETROTRANSPOSITION ,QH426 Genetics ,Biology ,Article ,Structural variation ,RC0254 ,03 medical and health sciences ,QH301 ,SDG 3 - Good Health and Well-being ,medicine ,Humans ,QH426 ,030304 developmental biology ,Tumors ,Science & Technology ,LANDSCAPE ,RC0254 Neoplasms. Tumors. Oncology (including Cancer) ,Genome, Human ,ResearchInstitutes_Networks_Beacons/mcrc ,DELETION ,Gene rearrangement ,DNA ,Gene Rearrangement/genetics ,Long interspersed nuclear element ,Reordenament genètic ,Long Interspersed Nucleotide Elements ,Long Interspersed Nucleotide Elements/genetics ,Genome, Human/genetics ,Carcinogenesis/genetics ,Genètica - Abstract
About half of all cancers have somatic integrations of retrotransposons. Here, to characterize their role in oncogenesis, we analyzed the patterns and mechanisms of somatic retrotransposition in 2,954 cancer genomes from 38 histological cancer subtypes within the framework of the Pan-Cancer Analysis of Whole Genomes (PCAWG) project. We identified 19,166 somatically acquired retrotransposition events, which affected 35% of samples and spanned a range of event types. Long interspersed nuclear element (LINE-1; L1 hereafter) insertions emerged as the first most frequent type of somatic structural variation in esophageal adenocarcinoma, and the second most frequent in head-and-neck and colorectal cancers. Aberrant L1 integrations can delete megabase-scale regions of a chromosome, which sometimes leads to the removal of tumor-suppressor genes, and can induce complex translocations and large-scale duplications. Somatic retrotranspositions can also initiate breakage–fusion–bridge cycles, leading to high-level amplification of oncogenes. These observations illuminate a relevant role of L1 retrotransposition in remodeling the cancer genome, with potential implications for the development of human tumors., An analysis of 2,954 genomes from 38 cancer subtypes identified 19,166 retrotransposition events in 35% of samples. Aberrant LINE-1 retrotranspositions can lead to the deletion of tumor-suppressor genes as well as the amplification of oncogenes.
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- 2020
7. A novel method to calculate transcription factor binding in chromatin: SW01.S1–17
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Beshnova, D. A., Rippe, K., and Teif, V. B.
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- 2013
8. Individuelle Therapieversuche: Ethische Probleme am Beispiel der Onkologie
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Rippe, K. P.
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- 2000
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- View/download PDF
9. Ligand-Induced Conformational Transition of DNA as Studied by Infrared Spectroscopy, Infrared Linear Dichroism, Circular Dichroism, and Fluorescence Spectroscopy
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Fritzsche, H., Zimmer, Ch., Burckhardt, G., Förtsch, I., Rippe, K., Jovin, Th. M., Merlin, Jean Claude, editor, Turrell, Sylvia, editor, and Huvenne, Jean Pierre, editor
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- 1995
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10. Structure and Interactions of Parallel-Stranded DNA Studied by Infrared Spectroscopy and Fluorescence
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Fritzsche, H., Akhebat, A., Taillandier, E., Rippe, K., Jovin, Th. M., Theophanides, Theophile, editor, Anastassopoulou, Jane, editor, and Fotopoulos, Nikolaos, editor
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- 1993
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11. 469 Epigenomic characterization of non-melanoma skin cancer
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Rodríguez Paredes, M., primary, Solé Boldo, L., additional, Raddatz, G., additional, Gutekunst, J., additional, Liberio, M., additional, Mallm, J., additional, Rippe, K., additional, Lonsdorf, A.S., additional, and Lyko, F., additional
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- 2019
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12. TRANSCRIPTIONAL AND GENOMIC INTRA-TUMOR HETEROGENEITY DRIVES SUBCLONE SPECIFIC DRUG RESPONSES IN DIFFUSE LARGE B CELL LYMPHOMA
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Roider, T., primary, Frauhammer, F., additional, Seufert, J., additional, Bordas, M., additional, Stolarczyk, M., additional, Rabe, S., additional, Malm, J., additional, Bruch, P., additional, Hundemer, M., additional, Rippe, K., additional, Goeppert, B., additional, Seiffert, M., additional, Brors, B., additional, Mechtersheimer, G., additional, Müller-Tidow, C., additional, Fröhling, S., additional, Schlesner, M., additional, Huber, W., additional, Anders, S., additional, and Dietrich, S., additional
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- 2019
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13. Structure-function relationships in the Bvg and Evg two-component phosphorelay systems
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Bantscheff, M., Perraud, A.-L., Bock, A., Rippe, K., Weiss, V., Glocker, M., and Gross, R.
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- 2000
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14. Comparison of segmentation methods for tissue microscopy images of glioblastoma cells
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Baltissen, D., primary, Wollmann, T., additional, Gunkel, M., additional, Chung, I., additional, Erfle, H., additional, Rippe, K., additional, and Rohr, K., additional
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- 2018
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- View/download PDF
15. Bayesian joint super-resolution, deconvolution, and denoising of images with Poisson-Gaussian noise
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Gao, Q., primary, Eck, S., additional, Matthias, J., additional, Chung, I., additional, Engelhardt, J., additional, Rippe, K., additional, and Rohr, K., additional
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- 2018
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- View/download PDF
16. Interplay and quality control of DNA damage repair mechanisms
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Eppink, Berina, Essers, J., Kanaar, Roland, Rippe, K., and Molecular Genetics
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- 2010
17. Eine Verteidigung der Staatlichen Neutralität
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van der Burg, W., Brom, F.W.A., P Rippe, K., and Tilburg Law School
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- 1999
18. Calculating transcription factor binding maps for chromatin
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Teif, V. B., primary and Rippe, K., additional
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- 2011
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- View/download PDF
19. Crystal structure of Toc33 from Arabidopsis thaliana, dimerization deficient mutant R130A
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Koenig, P., primary, Oreb, M., additional, Rippe, K., additional, Muhle-Goll, C., additional, Sinning, I., additional, Schleiff, E., additional, and Tews, I., additional
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- 2008
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20. The Hydrogen-Bonding Structure in Parallel-Stranded Duplex DNA is Reverse Watson Crick
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Otto, Cornelis, Thomas, G.A., Rippe, K., Jovin, T.M., and Peticolas, W.L.
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METIS-129442 - Published
- 1991
21. Individuelle Therapieversuche
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Rippe, K. P., primary
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- 2000
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- View/download PDF
22. DNA binding and oligomerization of NtrC studied by fluorescence anisotropy and fluorescence correlation spectroscopy
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Sevenich, F. W., primary, Langowski, J., additional, Rippe, K., additional, and Weiss, V., additional
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- 1998
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23. Superhelix dimensions of a 1868 base pair plasmid determined by scanning force microscopy in air and in aqueous solution
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Rippe, K., primary, Mucke, N., additional, and Langowski, J., additional
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- 1997
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24. Alternating d(G-A) sequences form a parallel-stranded DNA homoduplex.
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Rippe, K., primary, Fritsch, V., additional, Westhof, E., additional, and Jovin, T.M., additional
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- 1992
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25. The hydrogen-bonding structure in parallel-stranded duplex DNA is reverse Watson-Crick
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Otto, C., primary, Thomas, G. A., additional, Rippe, K., additional, Jovin, T. M., additional, and Peticolas, Werner L., additional
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- 1991
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26. Silencing the singer: Antibioethics in Germany.
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Schone-Seifert, B. and Rippe, K.
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- SINGER, Peter, 1946-
- Abstract
Reports that Peter Singer, the `death ethicist' has become a special target for activists trying to silence bioethical debate in Germany. The trauma inflicted by National Socialism and unease over the issues surrounding the end of life; Singer's permissive positions toward abortion and euthanasia; Singer's `Practical Ethics'; Beliefs of the anti-Singer front in Germany; The pro-choice movement; More.
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- 1991
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27. Biochemical characterization and mass spectrometric disulfide bond mapping of periplasmic alpha-amylase MalS of Escherichia coli.
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Spiess, C, Happersberger, H P, Glocker, M O, Spiess, E, Rippe, K, and Ehrmann, M
- Abstract
Periplasmic alpha-amylase of Escherichia coli, the malS gene product, hydrolyzes linear maltodextrins. The purified enzyme exhibited a Km of 49 microM and a Vmax of 0.36 micromol of p-nitrophenylhexaoside hydrolyzed per min per mg of protein. Amylase activity was optimal at pH 8 and was dependent on divalent cations such as Ca2+. MalS exhibited altered migration on SDS-polyacrylamide gel electrophoresis under nonreducing conditions. Analytical ultracentrifugation and electrospray mass spectrometry indicated that MalS is monomeric. The four cysteine residues are involved in intramolecular disulfide bonds. To map disulfide bonds, MalS was proteolytically digested. The resulting peptides were separated by reverse phase-high performance liquid chromatography, and matrix-assisted laser desorption/ionization mass spectrometry analysis indicated the presence of two disulfide bonds, i.e. Cys40-58 and Cys104-520. The disulfide bond at Cys40-58 is located in an N-terminal extension of about 160 amino acids which has no homology to other amylases but to the proposed peptide binding domain of GroEL, the Hsp60 of E. coli. The N-terminal extension is linked to the C-terminal amylase domain via disulfide bond Cys104-520. Reduction of disulfide bonds by dithiothreitol treatment led to aggregation suggesting that the N terminus of MalS may represent an internal chaperone domain.
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- 1997
28. Specificity mechanisms in the control of transcription
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Hippel, P. H. Von, Rees, W. A., Rippe, K., and Wilson, K. S.
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- 1996
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29. Refining animal models in fracture research: seeking consensus in optimising both animal welfare and scientific validity for appropriate biomedical use
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Schneider Erich, Hofmann-Amtenbrinck Margarethe, von Rechenberg Brigitte, Claes Lutz, Price Jill, Pearce Simon, Arnoczky Steven, Goodship Allen, Auer Jorg A, Müller-Terpitz R, Thiele F, Rippe Klaus-Peter, and Grainger David W
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Diseases of the musculoskeletal system ,RC925-935 - Abstract
Abstract Background In an attempt to establish some consensus on the proper use and design of experimental animal models in musculoskeletal research, AOVET (the veterinary specialty group of the AO Foundation) in concert with the AO Research Institute (ARI), and the European Academy for the Study of Scientific and Technological Advance, convened a group of musculoskeletal researchers, veterinarians, legal experts, and ethicists to discuss, in a frank and open forum, the use of animals in musculoskeletal research. Methods The group narrowed the field to fracture research. The consensus opinion resulting from this workshop can be summarized as follows: Results & Conclusion Anaesthesia and pain management protocols for research animals should follow standard protocols applied in clinical work for the species involved. This will improve morbidity and mortality outcomes. A database should be established to facilitate selection of anaesthesia and pain management protocols for specific experimental surgical procedures and adopted as an International Standard (IS) according to animal species selected. A list of 10 golden rules and requirements for conduction of animal experiments in musculoskeletal research was drawn up comprising 1) Intelligent study designs to receive appropriate answers; 2) Minimal complication rates (5 to max. 10%); 3) Defined end-points for both welfare and scientific outputs analogous to quality assessment (QA) audit of protocols in GLP studies; 4) Sufficient details for materials and methods applied; 5) Potentially confounding variables (genetic background, seasonal, hormonal, size, histological, and biomechanical differences); 6) Post-operative management with emphasis on analgesia and follow-up examinations; 7) Study protocols to satisfy criteria established for a "justified animal study"; 8) Surgical expertise to conduct surgery on animals; 9) Pilot studies as a critical part of model validation and powering of the definitive study design; 10) Criteria for funding agencies to include requirements related to animal experiments as part of the overall scientific proposal review protocols. Such agencies are also encouraged to seriously consider and adopt the recommendations described here when awarding funds for specific projects. Specific new requirements and mandates related both to improving the welfare and scientific rigour of animal-based research models are urgently needed as part of international harmonization of standards.
- Published
- 2007
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30. Pan-cancer analysis of whole genomes
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Campbell, P. J. a., Abpemail, Author, Getz, G. b., C, D, Eemail, Author, Korbel, J. O. f., Gemail, Author, Stuart, hEmail Author, J. M., Jennings, J. L. i., Stein, J, L. D. k., Lemail, Author, Perry, M. D. m., Nahal-Bose, N, Ouellette, H. K. n., B. F. F. o., P, C. H. k., Li, Rheinbay, Q, E. b., E, Nielsen, R, Sgroi, G. P. r., D. C. r., Wu, C. -L. r., Faquin, W. C. r., Deshpande, V. r., Boutros, P. C. k., Q, S, Lazar, T, Hoadley, A. J. u., K. A. v., W, Louis, D. N. r., Dursi, L. J. k., Yung, X, Bailey, C. K. n., M. H. y., Z, Saksena, G. b., Raine, Abp, K. M., Buchhalter, Aa, I., Ab, Ac, Kleinheinz, Aa, K., Schlesner, Ac, Aa, M., Zhang, Ad, Wang, J. n., Ae, W., Wheeler, D. A., Af, Ding, Ag, L. y., Z, Simpson, Ah, J. T. k., Ai, O’Connor, B. D. n., Yakneen, Aj, Ellrott, S. g., Ak, K., Miyoshi, Al, N., Butler, Abp, A. P., Royo, Am, R., Shorser, S. I. k., Vazquez, Am, M., Rausch, An, Tiao, T. g., Waszak, G. b., Rodriguez-Martin, S. 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E., Rk, Bourque, Rl, G., Brennan, Rm, Rn, P., Letourneau, Ro, L., Riazalhosseini, Rm, Y., Scelo, Rn, G., Vasudev, Rk, N., Viksna, Rp, Rq, J., Lathrop, Rm, M., Tost, Rr, J., Ahn, S. -M., Rs, Aparicio, Rt, S., Arnould, Ru, L., Aure, M. R., Rv, Bhosle, Abp, S. G., Birney, E. f., Borg, Rw, A., Boyault, Rx, S., Brinkman, A. B., Ry, Brock, J. E., Rz, Broeks, Sa, A., Børresen-Dale, A. -L., Rv, Caldas, Sb, C., Chin, Sc, S. -F., Sb, Davies, Sc, Mu, H., Abp, Mv, Desmedt, Sd, C., Dirix, Se, Sf, L., Dronov, Ehinger, Sg, A., Eyfjord, J. E., Sh, Fatima, Gt, A., Foekens, J. A., Si, Futreal, P. A., Sj, Garred, Sk, Ø., Giri, Sl, D. D., Sm, Glodzik, Abp, D., Grabau, Sn, D., Hilmarsdottir, Sh, H., Hooijer, G. K., So, Jacquemier, Sp, J., S. J., Sq, Jonasson, J. G., Sh, Jonkers, Sr, J., H. -Y., Sp, King, T. A., Ss, Knappskog, St, Su, S., Abp, Kong, Sp, G., Krishnamurthy, Sv, S., Lakhani, S. R., Sw, Langerød, Rv, A., Larsimont, Sx, D., H. J., Sq, J. -Y., Sy, M. T. M., Sj, Lingjærde, O. C., Sz, Macgrogan, Ta, G., Martens, J. W. M., Si, O’Meara, Pauporté, He, I., Pinder, Tb, S., Pivot, Tc, X., Provenzano, Td, E., Purdie, C. A., Te, Ramakrishna, Abp, M., Ramakrishnan, Abp, K., Reis-Filho, Sm, J., Richardson, A. L., Gt, Ringnér, Rw, M., Rodriguez, J. B., Am, Rodríguez-González, F. G., Iz, Romieu, Tf, G., Salgado, Os, R., Sauer, Sz, T., Shepherd, Abp, R., Sieuwerts, A. M., Si, Simpson, P. T., Sw, Smid, Si, M., Sotiriou, Span, P. N., Tg, Stefánsson, Ó. A., Th, Stenhouse, Ti, A., Stunnenberg, H. G., Fw, Sweep, Tj, Tk, F., Tan, B. K. T., Tl, Thomas, Tm, G., Thompson, A. M., Ti, Tommasi, Tn, S., Treilleux, To, I., Tutt, Tp, Ueno, N. T., Nv, Van, Laere, Sf, S., Van den Eynden, G. G., Sf, Vermeulen, Sf, P., Viari, Vincent-Salomon, Tj, A., Wong, B. H., Tq, Yates, Abp, X., Van, Deurzen, C. H. M., Tr, van de Vijver, M. J., Os, Van’T, Veer, Ts, L., Ammerpohl, Tt, O., Tu, Tv, Aukema, Tu, S., Tv, Tw, Bergmann, A. K., Tx, Bernhart, S. 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E., Ze, Ghossein, Zf, Sm, R., Giama, N. H., Zg, Gibbs, R. A., Ag, Gomez, Zh, C., Govindan, R. y., Hayes, D. N. w., Zi, Zj, Hegde, A. M., Ee, Heiman, Ef, Heins, D. I. b., Jq, Z., Hepperla, A. J. w., Holbrook, Ym, A., Holt, R. A., Yc, Hoyle, A. P. w., Hruban, R. H., Yv, Ag, J., Xg, M., Huntsman, Zk, D., Huse, Jq, J., Iacobuzio-Donahue, C. A., Sm, Ittmann, Zl, M., Jayaseelan, Zm, J. C., Ag, Jefferys, S. R. w., C. D., Zn, S. J. M., Zo, Juhl, Zp, H., Kang, K. J., Zq, Karlan, Zr, B., Kasaian, Zo, K., Kebebew, Zs, E., Kim, Zt, H. K., Zu, Korchina, Ag, V., Kundra, Wt, R., Lai, Yd, P. H., Ym, Lander, E. b., Zv, X., Levine, D. A., Jq, Lewis, Zw, Ag, L., Ley, Zx, T., H. I., Yc, Lin, P. b., Linehan, W. M., Zy, F. F., No, Ef, Y., Lype, Zz, L., Yc, Y., Maglinte, D. T., Ym, Aaa, Mardis, E. R. z., Yp, Aab, Marks, Ow, J., Aac, Marra, M. A., Yc, Matthew, T. J., Aj, Mayo, Mccune, Aad, K., Meier, S. R. b., Meng, S. w., Mieczkowski, P. A. v., Mikkelsen, Aae, T., Miller, C. A. z., Mills, Aaf, G. B., Morrison, Aag, Mose, Moser, L. E. w., C. D., Zg, Mungall, A. J., Yc, Yc, K., Mutch, Aah, D., Muzny, Aai, D. M., Myers, Aaj, J., Newton, Aj, Y., Noble, M. S. b., O’Donnell, Aak, P., Aal, B. P., Ochoa, Aam, J. -W., Parker, Aan, J. S., Pass, Aao, H., Pastore, Pennell, Aap, N. A., Perou, Aaq, C. M., Petrelli, Aar, N., Potapova, Aas, O., Rader, Aat, J. S., Ramalingam, Aau, S., Rathmell, Aav, W. K., Reuter, Sm, V., Reynolds, S. M., Zz, Ringel, Aaw, M., Roach, Aax, J., L. R., Zg, A. G., Yc, Sadeghi, Yc, S., Saller, Aay, C., Sanchez-Vega, Wt, F., Schadendorf, Yd, Eq, D., Aaz, Schein, J. E., Yc, Schmidt, H. K. z., Schultz, Yd, N., Seethala, Aba, R., Senbabaoglu, Dg, Y., Shelton, Yw, T., Shi, Y. w., Shih, J. b., Shmulevich, Fj, Zz, I., Shriver, Abb, C., Signoretti, Fj, S., Abc, Jb, Simons, J. V. w., Singer, Abd, Sipahimalani, Yc, P., Skelly, T. J. v., Smith-McCune, Socci, N. D., Dg, Soloway, Aan, M. G., Sood, Abe, A. K., Tam, Tan, D. v., Tarnuzzer, Hv, R., Thiessen, Abf, R. H., L. B., Xg, Tsao, Xe, M., Umbricht, Ye, Lk, C., Abg, Wv, Van Den Berg, D. J., Ym, Van, Meir, Abh, E. G., Veluvolu, U. v., Voet, D. b., Weinberger, Abi, P., Weisenberger, Wigle, Abj, D., Wilkerson, M. D. v., Wilson, R. K. z., Abk, Winterhoff, Abl, B., Wiznerowicz, Abm, M., Abn, Wong, T. z., Yc, Abo, W., Yau, Zhang, H. b., Yd, H., Hv, J., The ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium View Correspondence (jump link), Medical Oncology, Pathology, IBM, Pharmacyclics, Novartis, Celgene, AstraZeneca, Bayer, Janssen Biotech, University of Chicago, Ipsen, Pfizer, Ono Pharmaceutical, Ariad Pharmaceuticals, Gilead Sciences, Bristol-Myers Squibb, University of St Andrews. School of Medicine, University of St Andrews. Statistics, University of St Andrews. Sir James Mackenzie Institute for Early Diagnosis, University of St Andrews. Cellular Medicine Division, RS: CAPHRI - R4 - Health Inequities and Societal Participation, Metamedica, Háskóli Íslands, University of Iceland, Faculty of Medicine, University of Helsinki, Department of Medical and Clinical Genetics, Research Programs Unit, Lauri Antti Aaltonen / Principal Investigator, ATG - Applied Tumor Genomics, Helsinki Institute of Life Science HiLIFE, Organismal and Evolutionary Biology Research Programme, Helsinki Institute for Information Technology, Institute of Biotechnology, Bioinformatics, Department of Computer Science, STEMM - Stem Cells and Metabolism Research Program, Centre of Excellence in Stem Cell Metabolism, Genome-Scale Biology (GSB) Research Program, Department of Physics, HUS Helsinki and Uusimaa Hospital District, University of Zurich, ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium, Apollo - University of Cambridge Repository, Graduate School, Laboratory Genetic Metabolic Diseases, AGEM - Endocrinology, metabolism and nutrition, 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Hong, J, Hudson, T, Hubschmann, D, Ivkovic, S, Jeon, S, Jiao, W, Kabbe, R, Kerssemakers, J, Kim, J, Koscher, M, Koures, A, Kovacevic, M, Lawerenz, C, Liu, J, Mijalkovic, S, Mijalkovic-Lazic, A, Miyano, S, Nastic, M, Nicholson, J, Ocana, D, Ohi, K, Ohno-Machado, L, Pihl, T, Prinz, M, Radovic, P, Short, C, Sofia, H, Spring, J, Struck, A, Tijanic, N, Vicente, D, Wang, Z, Williams, A, Woo, Y, Wright, A, Yang, L, Hamilton, M, Johnson, T, Kahraman, A, Kellis, M, Polak, P, Sallari, R, Sinnott-Armstrong, N, von Mering, C, Beltran, S, Gerhard, D, Gut, M, Trotta, J, Whalley, J, Niu, B, Espiritu, S, Gao, S, Huang, Y, Teague, J, Abascal, F, Bader, G, Bandopadhayay, P, Barenboim, J, Brunak, S, Carlevaro-Fita, J, Chakravarty, D, Chan, C, Choi, J, Diamanti, K, Fink, J, Frigola, J, Gambacorti Passerini, C, Garsed, D, Haradhvala, N, Harmanci, A, Helmy, M, Herrmann, C, Hobolth, A, Hodzic, E, Hong, C, Isaev, K, Izarzugaza, J, Johnson, R, Juul, R, Jan, K, Lanzos, A, Larsson, E, Lee, D, Lin, Z, Liu, E, 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K, Bruxner, T, Christ, A, Cordner, S, Cowin, P, Drapkin, R, Fereday, S, George, J, Hamilton, A, Holmes, O, Hung, J, Kassahn, K, Kazakoff, S, Kennedy, C, Leonard, C, Mileshkin, L, Miller, D, Arnau, G, Mitchell, C, Newell, F, Nones, K, Patch, A, Quinn, M, Taylor, D, Thorne, H, Traficante, N, Vedururu, R, Waring, P, Wood, S, Xu, Q, Defazio, A, Anderson, M, Antonello, D, Barbour, A, Bassi, C, Bersani, S, Cataldo, I, Chantrill, L, Chiew, Y, Chou, A, Cingarlini, S, Cloonan, N, Corbo, V, Davi, M, Duthie, F, Gill, A, Graham, J, Harliwong, I, Jamieson, N, Johns, A, Kench, J, Landoni, L, Lawlor, R, Mafficini, A, Merrett, N, Miotto, M, Musgrove, E, Nagrial, A, Oien, K, Pajic, M, Pinese, M, Robertson, A, Rooman, I, Rusev, B, Samra, J, Scardoni, M, Scarlett, C, Scarpa, A, Sereni, E, Sikora, K, Simbolo, M, Taschuk, M, Toon, C, Vicentini, C, Wu, J, Zeps, N, Behren, A, Burke, H, Cebon, J, Dagg, R, De Paoli-Iseppi, R, Dutton-Regester, K, Field, M, Fitzgerald, A, Hersey, P, Jakrot, V, Johansson, P, Kakavand, H, Kefford, R, Lau, L, Long, G, Pickett, H, Pritchard, A, Pupo, G, Saw, R, Schramm, S, Shang, C, Shang, P, Spillane, A, Stretch, J, Tembe, V, Thompson, J, Vilain, R, Wilmott, J, Yang, J, Hayward, N, Mann, G, Scolyer, R, Bartlett, J, Bavi, P, Chadwick, D, Chan-Seng-Yue, M, Cleary, S, Connor, A, Czajka, K, Denroche, R, Dhani, N, Eagles, J, Gallinger, S, Grant, R, Hedley, D, Hollingsworth, M, Jang, G, Johns, J, Kalimuthu, S, Liang, S, Lungu, I, Luo, X, Mbabaali, F, Mcpherson, T, Miller, J, Moore, M, Notta, F, Pasternack, D, Petersen, G, Roehrl, M, Sam, M, Selander, I, Serra, S, Shahabi, S, Thayer, S, Timms, L, Wilson, G, Wilson, J, Wouters, B, Beck, T, Bhandari, V, Collins, C, Fleshner, N, Fox, N, Fraser, M, Heisler, L, Lalonde, E, Livingstone, J, Meng, A, Sabelnykova, V, Shiah, Y, Van der Kwast, T, Bristow, R, Ding, S, Fan, D, Li, L, Nie, Y, Xiao, X, Xing, R, Yang, S, Yu, Y, Zhou, Y, Banks, R, Bourque, G, Brennan, P, Letourneau, L, Riazalhosseini, Y, Scelo, G, Vasudev, N, Viksna, J, Lathrop, M, Tost, J, Ahn, S, Aparicio, S, Arnould, L, Aure, M, Bhosle, S, Birney, E, Borg, A, Boyault, S, Brinkman, A, Brock, J, Broeks, A, Borresen-Dale, A, Caldas, C, Chin, S, Davies, H, Desmedt, C, Dirix, L, Dronov, S, Ehinger, A, Eyfjord, J, Fatima, A, Foekens, J, Futreal, P, Garred, O, Giri, D, Glodzik, D, Grabau, D, Hilmarsdottir, H, Hooijer, G, Jacquemier, J, Jang, S, Jonasson, J, Jonkers, J, King, T, Knappskog, S, Kong, G, Krishnamurthy, S, Lakhani, S, Langerod, A, Larsimont, D, Lee, H, Lee, M, Lingjaerde, O, Macgrogan, G, Martens, J, O'Meara, S, Pauporte, I, Pinder, S, Pivot, X, Provenzano, E, Purdie, C, Ramakrishna, M, Ramakrishnan, K, Reis-Filho, J, Richardson, A, Ringner, M, Rodriguez, J, Rodriguez-Gonzalez, F, Romieu, G, Salgado, R, Sauer, T, Shepherd, R, Sieuwerts, A, Simpson, P, Smid, M, Sotiriou, C, Span, P, Stefansson, O, Stenhouse, A, Stunnenberg, H, Sweep, F, Tan, B, Thomas, G, Thompson, A, Tommasi, S, Treilleux, I, Tutt, A, Ueno, N, Van Laere, S, Van den Eynden, G, Vermeulen, P, Viari, A, Vincent-Salomon, A, Wong, B, Yates, L, Zou, X, van Deurzen, C, van de Vijver, M, van't Veer, L, Ammerpohl, O, Aukema, S, Bergmann, A, Bernhart, S, Borkhardt, A, Borst, C, Burkhardt, B, Claviez, A, Goebler, M, Haake, A, Haas, S, Hansmann, M, Hoell, J, Hummel, M, Karsch, D, Klapper, W, Kneba, M, Kreuz, M, Kube, D, Kuppers, R, Lenze, D, Loeffler, M, Lopez, C, Mantovani-Loffler, L, Moller, P, Ott, G, Radlwimmer, B, Richter, J, Rohde, M, Rosenstiel, P, Rosenwald, A, Schilhabel, M, Schreiber, S, Stadler, P, Staib, P, Stilgenbauer, S, Sungalee, S, Szczepanowski, M, Toprak, U, Trumper, L, Wagener, R, Zenz, T, Hovestadt, V, von Kalle, C, Kool, M, Korshunov, A, Landgraf, P, Lehrach, H, Northcott, P, Pfister, S, Reifenberger, G, Warnatz, H, Wolf, S, Yaspo, M, Assenov, Y, Gerhauser, C, Minner, S, Schlomm, T, Simon, R, Sauter, G, Sultmann, H, Biswas, N, Maitra, A, Majumder, P, Sarin, R, Barbi, S, Bonizzato, G, Cantu, C, Dei Tos, A, Fassan, M, Grimaldi, S, Luchini, C, Malleo, G, Marchegiani, G, Milella, M, Paiella, S, Pea, A, Pederzoli, P, Ruzzenente, A, Salvia, R, Sperandio, N, Arai, Y, Hama, N, Hiraoka, N, Hosoda, F, Nakamura, H, Ojima, H, Okusaka, T, Totoki, Y, Urushidate, T, Fukayama, M, Ishikawa, S, Katai, H, Katoh, H, Komura, D, Rokutan, H, Saito-Adachi, M, Suzuki, A, Taniguchi, H, Tatsuno, K, Ushiku, T, Yachida, S, Yamamoto, S, Aikata, H, Arihiro, K, Ariizumi, S, Chayama, K, Furuta, M, Gotoh, K, Hayami, S, Hirano, S, Kawakami, Y, Maejima, K, Nakamura, T, Nakano, K, Ohdan, H, Sasaki-Oku, A, Tanaka, H, Ueno, M, Yamamoto, M, Yamaue, H, Choo, S, Cutcutache, I, Khuntikeo, N, Ong, C, Pairojkul, C, Popescu, I, Ahn, K, Aymerich, M, Lopez-Guillermo, A, Lopez-Otin, C, Puente, X, Campo, E, Amary, F, Baumhoer, D, Behjati, S, Bjerkehagen, B, Myklebost, O, Pillay, N, Tarpey, P, Tirabosco, R, Zaikova, O, Flanagan, A, Boultwood, J, Bowen, D, Cazzola, M, Green, A, Hellstrom-Lindberg, E, Malcovati, L, Nangalia, J, Papaemmanuil, E, Vyas, P, Ang, Y, Barr, H, Beardsmore, D, Eldridge, M, Gossage, J, Grehan, N, Hanna, G, Hayes, S, Hupp, T, Khoo, D, Lagergren, J, Lovat, L, Macrae, S, O'Donovan, M, O'Neill, J, Parsons, S, Preston, S, Puig, S, Roques, T, Sanders, G, Sothi, S, Tavare, S, Tucker, O, Turkington, R, Underwood, T, Welch, I, Fitzgerald, R, Berney, D, De Bono, J, Cahill, D, Camacho, N, Dennis, N, Dudderidge, T, Edwards, S, Fisher, C, Foster, C, Ghori, M, Gill, P, Gnanapragasam, V, Gundem, G, Hamdy, F, Hawkins, S, Hazell, S, Howat, W, Isaacs, W, Karaszi, K, Kay, J, Khoo, V, Kote-Jarai, Z, Kremeyer, B, Kumar, P, Lambert, A, Leongamornlert, D, Livni, N, Luxton, H, Marsden, L, Massie, C, Matthews, L, Mayer, E, Mcdermott, U, Merson, S, Neal, D, Nicol, D, Ogden, C, Rowe, E, Shah, N, Thomas, S, Verrill, C, Visakorpi, T, Warren, A, Whitaker, H, Zhang, H, van As, N, Eeles, R, Abeshouse, A, Agrawal, N, Akbani, R, Al-Ahmadie, H, Albert, M, Aldape, K, Ally, A, Appelbaum, E, Armenia, J, Asa, S, Auman, J, Balasundaram, M, Balu, S, Barnholtz-Sloan, J, Bathe, O, Baylin, S, Benz, C, Berchuck, A, Berrios, M, Bigner, D, Birrer, M, Bodenheimer, T, Boice, L, Bootwalla, M, Bosenberg, M, Bowlby, R, Boyd, J, Broaddus, R, Brock, M, Brooks, D, Bullman, S, Caesar-Johnson, S, Carey, T, Carlsen, R, Cerfolio, R, Chandan, V, Chen, H, Cherniack, A, Chien, J, Cho, J, Chuah, E, Cibulskis, C, Cope, L, Cordes, M, Curley, E, Czerniak, B, Danilova, L, Davis, I, Defreitas, T, Demchok, J, Dhalla, N, Dhir, R, Doddapaneni, H, El-Naggar, A, Felau, I, Ferguson, M, Finocchiaro, G, Fong, K, Frazer, S, Friedman, W, Fronick, C, Fulton, L, Gabriel, S, Gao, J, Gehlenborg, N, Gershenwald, J, Ghossein, R, Giama, N, Gibbs, R, Gomez, C, Govindan, R, Hayes, D, Hegde, A, Heiman, D, Heins, Z, Hepperla, A, Holbrook, A, Holt, R, Hoyle, A, Hruban, R, Hu, J, Huntsman, D, Huse, J, Iacobuzio-Donahue, C, Ittmann, M, Jayaseelan, J, Jefferys, S, Jones, C, Jones, S, Juhl, H, Kang, K, Karlan, B, Kasaian, K, Kebebew, E, Korchina, V, Kundra, R, Lai, P, Lander, E, Le, X, Levine, D, Lewis, L, Ley, T, Li, H, Lin, P, Linehan, W, Lype, L, Ma, Y, Maglinte, D, Mardis, E, Marks, J, Marra, M, Matthew, T, Mayo, M, Mccune, K, Meier, S, Meng, S, Mieczkowski, P, Mikkelsen, T, Miller, C, Mills, G, Moore, R, Morrison, C, Mose, L, Moser, C, Mungall, A, Mungall, K, Mutch, D, Muzny, D, Myers, J, Newton, Y, Noble, M, O'Donnell, P, O'Neill, B, Ochoa, A, Parker, J, Pass, H, Pastore, A, Pennell, N, Perou, C, Petrelli, N, Potapova, O, Rader, J, Ramalingam, S, Rathmell, W, Reuter, V, Reynolds, S, Ringel, M, Roach, J, Roberts, L, Sadeghi, S, Saller, C, Sanchez-Vega, F, Schadendorf, D, Schein, J, Schmidt, H, Schultz, N, Seethala, R, Senbabaoglu, Y, Shelton, T, Shi, Y, Shih, J, Shmulevich, I, Shriver, C, Signoretti, S, Simons, J, Singer, S, Sipahimalani, P, Skelly, T, Smith-McCune, K, Socci, N, Soloway, M, Sood, A, Tam, A, Tan, D, Tarnuzzer, R, Thiessen, N, Thompson, R, Thorne, L, Tsao, M, Umbricht, C, Van Den Berg, D, Van Meir, E, Veluvolu, U, Voet, D, Wang, L, Weinberger, P, Weisenberger, D, Wigle, D, Wilkerson, M, Wilson, R, Winterhoff, B, Wiznerowicz, M, Wong, T, Wong, W, Xi, L, Yau, C, Consortium, ICGC/TCGA Pan-Cancer Analysis of Whole Genomes, Demeulemeester, Jonas, Desmedt, Christine, Van Loo, Peter, Barcelona Supercomputing Center, Imperial College Healthcare NHS Trust- BRC Funding, Cancer Research UK, Basic (bio-) Medical Sciences, and Laboratory for Medical and Molecular Oncology
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Male ,tert promoter mutations ,Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2] ,DNA Mutational Analysis ,Normal tissue ,systematic analysis ,Germline ,Transcriptome ,0302 clinical medicine ,Aetiology ,Càncer ,Cellular Senescence ,Cancer ,0303 health sciences ,dna-damage ,Massive parallel sequencing ,Pan cancer ,REARRANGEMENTS ,High-Throughput Nucleotide Sequencing ,Genomics ,Sciences bio-médicales et agricoles ,Telomere ,COMPREHENSIVE ,3. Good health ,TERT PROMOTER MUTATIONS ,signatures ,030220 oncology & carcinogenesis ,Science & Technology - Other Topics ,Erfðarannsóknir ,Human ,Informàtica::Aplicacions de la informàtica::Bioinformàtica [Àrees temàtiques de la UPC] ,Evolution ,RNA Splicing ,Article ,Evolution, Molecular ,Structural variation ,RC0254 ,03 medical and health sciences ,SDG 3 - Good Health and Well-being ,Genetic ,genomics ,SYSTEMATIC ANALYSIS ,Genetics ,Genomics--Databases ,Humans ,Genetic Testing ,Molecular Biology ,SIGNATURES ,Whole genome sequencing ,1000 Multidisciplinary ,Chromothripsis ,Science & Technology ,RC0254 Neoplasms. Tumors. Oncology (including Cancer) ,Information Dissemination ,ResearchInstitutes_Networks_Beacons/mcrc ,Prevention ,Biology and Life Sciences ,Molecular ,Oncogenes ,Cloud Computing ,medicine.disease ,Genòmica ,Compute clouds ,Mutation ,570 Life sciences ,biology ,COMPREHENSIVE CHARACTERIZATION ,Genètica ,Whole Genome Sequencing--methods ,Background information ,Genetic / genetics ,Genome ,Germ-Line Mutation / genetics ,Human / genetics ,ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium ,Medizin ,Whole-genome ,Genome mapping ,Neoplasms ,2.1 Biological and endogenous factors ,Promoter Regions, Genetic ,Càncer -- Aspectes genètics ,Telomerase ,Women's cancers Radboud Institute for Molecular Life Sciences [Radboudumc 17] ,Multidisciplinary ,Manchester Cancer Research Centre ,genomics, cancer, profiling ,3rd-DAS ,10124 Institute of Molecular Life Sciences ,Women's cancers Radboud Institute for Health Sciences [Radboudumc 17] ,Multidisciplinary Sciences ,Parallel sequencing ,Female ,profiling ,Medical Genetics ,Engineering sciences. Technology ,Biotechnology ,General Science & Technology ,The Cancer Genome Atlas ,610 Medicine & health ,Computational biology ,QH426 Genetics ,Biology ,Consortium of the International Cancer Genome Consortium ,Promoter Regions ,Germline mutation ,Pan-cancer analysis ,Krabbameinsrannsóknir ,medicine ,cancer ,ddc:610 ,QH426 ,Germ-Line Mutation ,Medicinsk genetik ,Krabbamein ,030304 developmental biology ,Cell Proliferation ,LANDSCAPE ,Genome, Human ,comprehensive characterization ,Pan-cancer analysis of whole genomes ,Point mutation ,Human Genome ,Reproducibility of Results ,SOMATIC MUTATIONS ,EVOLUTION ,Cancer, sequencing, Chromothripsis, telomere ,DNA-DAMAGE ,Mutagenesis ,PATTERNS ,3111 Biomedicine ,CHARACTERIZATION - Abstract
Publisher's version (útgefin grein), Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1,2,3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10,11,12,13,14,15,16,17,18., Competing interests Gad Getz receives research funds from IBM and Pharmacyclics and is an inventor on patent applications related to MuTect, ABSOLUTE, MutSig, MSMuTect, MSMutSig and POLYSOLVER. Hikmat Al-Ahmadie is consultant for AstraZeneca and Bristol-Myers Squibb. Samuel Aparicio is a founder and shareholder of Contextual Genomics. Pratiti Bandopadhayay receives grant funding from Novartis for an unrelated project. Rameen Beroukhim owns equity in Ampressa Therapeutics. Andrew Biankin receives grant funding from Celgene, AstraZeneca and is a consultant for or on advisory boards of AstraZeneca, Celgene, Elstar Therapeutics, Clovis Oncology and Roche. Ewan Birney is a consultant for Oxford Nanopore, Dovetail and GSK. Marcus Bosenberg is a consultant for Eli Lilly. Atul Butte is a cofounder of and consultant for Personalis, NuMedii, a consultant for Samsung, Geisinger Health, Mango Tree Corporation, Regenstrief Institute and in the recent past a consultant for 10x Genomics and Helix, a shareholder in Personalis, a minor shareholder in Apple, Twitter, Facebook, Google, Microsoft, Sarepta, 10x Genomics, Amazon, Biogen, CVS, Illumina, Snap and Sutro and has received honoraria and travel reimbursement for invited talks from Genentech, Roche, Pfizer, Optum, AbbVie and many academic institutions and health systems. Carlos Caldas has served on the Scientific Advisory Board of Illumina. Lorraine Chantrill acted on an advisory board for AMGEN Australia in the past 2 years. Andrew D. Cherniack receives research funding from Bayer. Helen Davies is an inventor on a number of patent applications that encompass the use of mutational signatures. Francisco De La Vega was employed at Annai Systems during part of the project. Ronny Drapkin serves on the scientific advisory board of Repare Therapeutics and Siamab Therapeutics. Rosalind Eeles has received an honorarium for the GU-ASCO meeting in San Francisco in January 2016 as a speaker, a honorarium and support from Janssen for the RMH FR meeting in November 2017 as a speaker (title: genetics and prostate cancer), a honorarium for an University of Chicago invited talk in May 2018 as speaker and an educational honorarium paid by Bayer & Ipsen to attend GU Connect ‘Treatment sequencing for mCRPC patients within the changing landscape of mHSPC’ at a venue at ESMO, Barcelona, on 28 September 2019. Paul Flicek is a member of the scientific advisory boards of Fabric Genomics and Eagle Genomics. Ronald Ghossein is a consultant for Veracyte. Dominik Glodzik is an inventor on a number of patent applications that encompass the use of mutational signatures. Eoghan Harrington is a full-time employee of Oxford Nanopore Technologies and is a stock holder. Yann Joly is responsible for the Data Access Compliance Office (DACO) of ICGC 2009-2018. Sissel Juul is a full-time employee of Oxford Nanopore Technologies and is a stock holder. Vincent Khoo has received personal fees and non-financial support from Accuray, Astellas, Bayer, Boston Scientific and Janssen. Stian Knappskog is a coprincipal investigator on a clinical trial that receives research funding from AstraZeneca and Pfizer. Ignaty Leshchiner is a consultant for PACT Pharma. Carlos López-Otín has ownership interest (including stock and patents) in DREAMgenics. Matthew Meyerson is a scientific advisory board chair of, and consultant for, OrigiMed, has obtained research funding from Bayer and Ono Pharma and receives patent royalties from LabCorp. Serena Nik-Zainal is an inventor on a number of patent applications that encompass the use of mutational signatures. Nathan Pennell has done consulting work with Merck, Astrazeneca, Eli Lilly and Bristol-Myers Squibb. Xose S. Puente has ownership interest (including stock and patents in DREAMgenics. Benjamin J. Raphael is a consultant for and has ownership interest (including stock and patents) in Medley Genomics. Jorge Reis-Filho is a consultant for Goldman Sachs and REPARE Therapeutics, member of the scientific advisory board of Volition RX and Paige.AI and an ad hoc member of the scientific advisory board of Ventana Medical Systems, Roche Tissue Diagnostics, InVicro, Roche, Genentech and Novartis. Lewis R. Roberts has received grant support from ARIAD Pharmaceuticals, Bayer, BTG International, Exact Sciences, Gilead Sciences, Glycotest, RedHill Biopharma, Target PharmaSolutions and Wako Diagnostics and has provided advisory services to Bayer, Exact Sciences, Gilead Sciences, GRAIL, QED Therapeutics and TAVEC Pharmaceuticals. Richard A. Scolyer has received fees for professional services from Merck Sharp & Dohme, GlaxoSmithKline Australia, Bristol-Myers Squibb, Dermpedia, Novartis Pharmaceuticals Australia, Myriad, NeraCare GmbH and Amgen. Tal Shmaya is employed at Annai Systems. Reiner Siebert has received speaker honoraria from Roche and AstraZeneca. Sabina Signoretti is a consultant for Bristol-Myers Squibb, AstraZeneca, Merck, AACR and NCI and has received funding from Bristol-Myers Squibb, AstraZeneca, Exelixis and royalties from Biogenex. Jared Simpson has received research funding and travel support from Oxford Nanopore Technologies. Anil K. Sood is a consultant for Merck and Kiyatec, has received research funding from M-Trap and is a shareholder in BioPath. Simon Tavaré is on the scientific advisory board of Ipsen and a consultant for Kallyope. John F. Thompson has received honoraria and travel support for attending advisory board meetings of GlaxoSmithKline and Provectus and has received honoraria for participation in advisory boards for MSD Australia and BMS Australia. Daniel Turner is a full-time employee of Oxford Nanopore Technologies and is a stock holder. Naveen Vasudev has received speaker honoraria and/or consultancy fees from Bristol-Myers Squibb, Pfizer, EUSA pharma, MSD and Novartis. Jeremiah A. Wala is a consultant for Nference. Daniel J. Weisenberger is a consultant for Zymo Research. Dai-Ying Wu is employed at Annai Systems. Cheng-Zhong Zhang is a cofounder and equity holder of Pillar Biosciences, a for-profit company that specializes in the development of targeted sequencing assays. The other authors declare no competing interests.
- Published
- 2020
31. Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples
- Author
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K, Marchegiani, G, Mardis, E, Margolin, A, Marin, M, Markowetz, F, Markowski, J, Marks, J, Marques-Bonet, T, Marra, M, Marsden, L, Martens, J, Martin, S, Martin-Subero, J, Martincorena, I, Martinez-Fundichely, A, Massie, C, Matthew, T, Matthews, L, Mayer, E, Mayes, S, Mayo, M, Mbabaali, F, Mccune, K, Mcdermott, U, Mcgillivray, P, Mcpherson, J, Mcpherson, T, Meier, S, Meng, A, Meng, S, Merrett, N, Merson, S, Meyerson, M, Mieczkowski, P, Mihaiescu, G, Mijalkovic, S, Mijalkovic-Lazic, A, Mikkelsen, T, Milella, M, Mileshkin, L, Miller, C, Miller, D, Miller, J, Minner, S, Miotto, M, Arnau, G, Mirabello, L, Mitchell, C, Mitchell, T, Miyano, S, Miyoshi, N, Mizuno, S, Molnar-Gabor, F, Moore, M, Moore, R, Morganella, S, Morris, Q, Morrison, C, Mose, L, Moser, C, Muinos, F, Mularoni, L, Mungall, A, Mungall, K, Musgrove, E, Mustonen, V, Mutch, D, Muyas, F, Muzny, D, Munoz, A, Myers, J, Myklebost, O, Moller, P, Nagae, G, Nagrial, A, Nahal-Bose, H, Nakagama, H, Nakagawa, H, Nakamura, H, Nakamura, T, Nakano, K, Nandi, T, Nangalia, J, Nastic, M, Navarro, A, Navarro, F, Neal, D, Nettekoven, G, Newell, F, Newhouse, S, Newton, Y, Ng, A, Nicholson, J, Nicol, D, Nie, Y, Nielsen, G, Nik-Zainal, S, Noble, M, Nones, K, Northcott, P, Notta, F, O'Connor, B, O'Donnell, P, O'Donovan, M, O'Meara, S, O'Neill, B, O'Neill, J, Ocana, D, Ochoa, A, Oesper, L, Ogden, C, Ohdan, H, Ohi, K, Ohno-Machado, L, Oien, K, Ojesina, A, Ojima, H, Okusaka, T, Omberg, L, Ong, C, Ott, G, Ouellette, B, P'Ng, C, Paczkowska, M, Paiella, S, Pairojkul, C, Pajic, M, Pan-Hammarstrom, Q, Papaemmanuil, E, Papatheodorou, I, Park, J, Park, K, Park, P, Parker, J, Parsons, S, Pass, H, Pasternack, D, Pastore, A, Patch, A, Pauporte, I, Pea, A, Pearson, J, Pedamallu, C, Pederzoli, P, Peifer, M, Pennell, N, Perou, C, Petersen, G, Petrelli, N, Petryszak, R, Pfister, S, Phillips, M, Pich, O, Pickett, H, Pihl, T, Pillay, N, Pinder, S, Pinese, M, Pinho, A, Pitkanen, E, Pivot, X, Pineiro-Yanez, E, Planko, L, Plass, C, Polak, P, Pons, T, Popescu, I, Potapova, O, Prasad, A, Preston, S, Prinz, M, Pritchard, A, Prokopec, S, Provenzano, E, Puente, X, Puig, S, Pulido-Tamayo, S, Pupo, G, Purdie, C, Quinn, M, Rabionet, R, Rader, J, Radlwimmer, B, Radovic, P, Raeder, B, Ramakrishna, M, Ramakrishnan, K, Ramalingam, S, Raphael, B, Rathmell, W, Rausch, T, Reifenberger, G, Reimand, J, Reis-Filho, J, Reuter, V, Reyes-Salazar, I, Reyna, M, Riazalhosseini, Y, Richardson, A, Richter, J, Ringel, M, Ringner, M, Rino, Y, Rippe, K, Roach, J, Roberts, L, Roberts, N, Roberts, S, Robertson, A, Rodriguez, J, Rodriguez-Martin, B, Rodriguez-Gonzalez, F, Roehrl, M, Rohde, M, Rokutan, H, Romieu, G, Rooman, I, Roques, T, Rosebrock, D, Rosenberg, M, Rosenstiel, P, Rosenwald, A, Rowe, E, Rozen, S, Rubanova, Y, Rubin, M, Rubio-Perez, C, Rudneva, V, Rusev, B, Ruzzenente, A, Ratsch, G, Sabarinathan, R, Sabelnykova, V, Sadeghi, S, Saini, N, Saito-Adachi, M, Salcedo, A, Salgado, R, Salichos, L, Sallari, R, Saller, C, Salvia, R, Sam, M, Samra, J, Sanchez-Vega, F, Sander, C, Sanders, G, Sarin, R, Sasaki-Oku, A, Sauer, T, Sauter, G, Saw, R, Scardoni, M, Scarlett, C, Scarpa, A, Scelo, G, Schadendorf, D, Schein, J, Schilhabel, M, Schlomm, T, Schmidt, H, Schramm, S, Schreiber, S, Schultz, N, Schumacher, S, Schwarz, R, Scolyer, R, Scott, D, Scully, R, Seethala, R, Segre, A, Selander, I, Semple, C, Senbabaoglu, Y, Sengupta, S, Sereni, E, Serra, S, Sgroi, D, Shackleton, M, Shah, N, Shahabi, S, Shang, C, Shang, P, Shapira, O, Shelton, T, Shen, C, Shen, H, Shepherd, R, Shi, R, Shi, Y, Shiah, Y, Shibata, T, Shih, J, Shimizu, E, Shimizu, K, Shin, S, Shiraishi, Y, Shmaya, T, Shmulevich, I, Shorser, S, Short, C, Shrestha, R, Shringarpure, S, Shriver, C, Shuai, S, Sidiropoulos, N, Siebert, R, Sieuwerts, A, Sieverling, L, Signoretti, S, Sikora, K, Simbolo, M, Simon, R, Simons, J, Simpson, P, Singer, S, Sinnott-Armstrong, N, Sipahimalani, P, Skelly, T, Smid, M, Smith, J, Smith-McCune, K, Socci, N, Soloway, M, Song, L, Sood, A, Sothi, S, Sotiriou, C, Soulette, C, Span, P, Spellman, P, Sperandio, N, Spillane, A, Spiro, O, Spring, J, Staaf, J, Stadler, P, Staib, P, Stark, S, Stefansson, O, Stegle, O, Stein, L, Stenhouse, A, Stilgenbauer, S, Stratton, M, Stretch, J, Stunnenberg, H, Su, H, Su, X, Sun, R, Sungalee, S, Susak, H, Suzuki, A, Sweep, F, Szczepanowski, M, Sultmann, H, Yugawa, T, Tam, A, Tamborero, D, Tan, B, Tan, D, Tan, P, Tanaka, H, Taniguchi, H, Tanskanen, T, Tarabichi, M, Tarnuzzer, R, Tarpey, P, Taschuk, M, Tatsuno, K, Tavare, S, Taylor, D, Taylor-Weiner, A, Teh, B, Tembe, V, Temes, J, Thai, K, Thayer, S, Thiessen, N, Thomas, G, Thomas, S, Thompson, A, Thompson, J, Thompson, R, Thorne, H, Thorne, L, Thorogood, A, Tijanic, N, Timms, L, Tirabosco, R, Tojo, M, Tommasi, S, Toon, C, Toprak, U, Tortora, G, Tost, J, Totoki, Y, Townend, D, Traficante, N, Treilleux, I, Trotta, J, Trumper, L, Tsao, M, Tsunoda, T, Tubio, J, Tucker, O, Turkington, R, Turner, D, Tutt, A, Ueno, M, Ueno, N, Umbricht, C, Umer, H, Underwood, 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Yamamoto, S, Yamaue, H, Yang, F, Yang, H, Yang, J, Yang, L, Yang, S, Yang, T, Yang, Y, Yao, X, Yaspo, M, Yates, L, Yau, C, Ye, C, Yoon, C, Yoon, S, Yousif, F, Yu, J, Yu, K, Yu, W, Yu, Y, Yuan, K, Yuan, Y, Yuen, D, Zaikova, O, Zamora, J, Zapatka, M, Zenklusen, J, Zenz, T, Zeps, N, Zhang, C, Zhang, F, Zhang, H, Zhang, X, Zhang, Y, Zhang, Z, Zhao, Z, Zheng, L, Zheng, X, Zhou, W, Zhou, Y, Bin, Z, Zhu, H, Zhu, J, Zhu, S, Zou, L, Zou, X, Defazio, A, van As, N, van Deurzen, C, van de Vijver, M, van't Veer, L, von Mering, C, Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Háskóli Íslands, University of Iceland, Tampere University, BioMediTech, TAYS Cancer Centre, University of St Andrews. Sir James Mackenzie Institute for Early Diagnosis, University of St Andrews. Cellular Medicine Division, University of St Andrews. Statistics, University of St Andrews. School of Medicine, University of Zurich, Gerstein, Mark B, Ding, Li, Bailey, Matthew H [0000-0003-4526-9727], Wheeler, David A [0000-0002-9056-6299], Gerstein, Mark B [0000-0002-9746-3719], Faculty of Economic and Social Sciences and Solvay Business School, Lauri Antti Aaltonen / Principal Investigator, Genome-Scale Biology (GSB) Research Program, Department of Medical and Clinical Genetics, Organismal and Evolutionary Biology Research Programme, Helsinki Institute for Information Technology, Institute of Biotechnology, Bioinformatics, Department of Computer Science, Faculty of Medicine, and HUS Helsinki and Uusimaa Hospital District
- Subjects
VARIANTS ,0302 clinical medicine ,706/648/697/129/2043 ,Databases, Genetic ,Cancer genomics ,SOMATIC POINT MUTATIONS ,Càncer ,lcsh:Science ,Exome ,Exome sequencing ,Cancer ,Base Composition ,Neoplasms -- genetics ,1184 Genetics, developmental biology, physiology ,3100 General Physics and Astronomy ,3. Good health ,030220 oncology & carcinogenesis ,Science & Technology - Other Topics ,Transformació genètica ,Genetic databases ,Erfðarannsóknir ,Human ,GENES ,Science ,1600 General Chemistry ,General Biochemistry, Genetics and Molecular Biology ,RC0254 ,03 medical and health sciences ,Genetic ,SDG 3 - Good Health and Well-being ,1300 General Biochemistry, Genetics and Molecular Biology ,Exome Sequencing ,Genetics ,Humans ,Author Correction ,Retrospective Studies ,Whole genome sequencing ,Comparative genomics ,Science & Technology ,RC0254 Neoplasms. Tumors. Oncology (including Cancer) ,INSERTIONS ,DNA ,PERFORMANCE ,Human genetics ,Communication and replication ,Cancérologie ,692/4028/67/69 ,Genòmica ,030104 developmental biology ,Mutation ,Genome mutation ,Human genome ,lcsh:Q ,COMPREHENSIVE CHARACTERIZATION ,Genètica ,0301 basic medicine ,Medizin ,General Physics and Astronomy ,Genome ,Whole Exome Sequencing ,Genetic transformation ,International Cancer Genome Consortium ,Neoplasms ,631/114/2399 ,Genamengi ,Medicine and Health Sciences ,Medicine(all) ,Women's cancers Radboud Institute for Molecular Life Sciences [Radboudumc 17] ,Multidisciplinary ,318 Medical biotechnology ,Exome -- genetics ,article ,Exons ,Women's cancers Radboud Institute for Health Sciences [Radboudumc 17] ,Multidisciplinary Sciences ,CAPTURE ,1181 Ecology, evolutionary biology ,oncology ,DNA, Intergenic ,139 ,Medical Genetics ,Biotechnology ,ICGC/TCGA Pan-Cancer Analysis ,3122 Cancers ,610 Medicine & health ,45/23 ,QH426 Genetics ,Biology ,MC3 Working Group ,Databases ,Germline mutation ,PCAWG novel somatic mutation calling methods working group ,Krabbameinsrannsóknir ,Cancer Genome Atlas ,Genome, Human -- genetics ,ddc:610 ,QH426 ,Medicinsk genetik ,Krabbamein ,Intergenic ,Whole Genome Sequencing ,Genome, Human ,Human Genome ,PCAWG Consortium ,DAS ,General Chemistry ,DELETIONS ,Good Health and Well Being ,10032 Clinic for Oncology and Hematology ,3111 Biomedicine ,631/1647/2217/748 - Abstract
MC3 Working Group: Rehan Akbani21, Pavana Anur22, Matthew H. Bailey1,2,3, Alex Buchanan9, Kami Chiotti9, Kyle Covington12,23, Allison Creason9, Li Ding1,2,3,20, Kyle Ellrott9, Yu Fan21, Steven Foltz1,2, Gad Getz8,14,15,16, Walker Hale12, David Haussler24,25, Julian M. Hess8,26, Carolyn M. Hutter27, Cyriac Kandoth28, Katayoon Kasaian29,30, Melpomeni Kasapi27, Dave Larson1 , Ignaty Leshchiner8, John Letaw31, Singer Ma32, Michael D. McLellan1,3,20, Yifei Men32, Gordon B. Mills33,34, Beifang Niu35, Myron Peto22, Amie Radenbaugh24, Sheila M. Reynolds36, Gordon Saksena8, Heidi Sofia27, Chip Stewart8, Adam J. Struck31, Joshua M. Stuart24,37, Wenyi Wang21, John N. Weinstein38, David A. Wheeler12,13, Christopher K. Wong24,39, Liu Xi12 & Kai Ye40,41 21Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. 22Molecular and Medical Genetics, OHSU Knight Cancer Institute, Oregon Health and Science University, Portland, OR 97239, USA. 23Castle Biosciences Inc, Friendswood, TX 77546, USA. 24UC Santa Cruz Genomics Institute, University of California Santa Cruz, Santa Cruz, CA 95064, USA. 25Howard Hughes Medical Institute, University of California Santa Cruz, Santa Cruz, CA 95064, USA. 26Massachusetts General Hospital Center for Cancer Research, Charlestown, MA 02114, USA. 27National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20894, USA. 28Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. 29Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada. 30Canada’s Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC V5Z 4S6, Canada. 31Computational Biology Program, School of Medicine, Oregon Health and Science University, Portland, OR 97239, USA. 32DNAnexus Inc, Mountain View, CA 94040, USA. 33Department of Systems Biology, UT MD Anderson Cancer Center, Houston, TX 77030, USA. 34Precision Oncology, OHSU Knight Cancer Institute, Oregon Health and Science University, Portland, OR 97239, USA. 35Computer Network Information Center, Chinese Academy of Sciences, Beijing, China. 36Institute for Systems Biology, Seattle, WA 98109, USA. 37Department of Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, CA 95064, USA. 38Department of Bioinformatics and Computational Biology and Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. 39Biomolecular Engineering Department, University of California Santa Cruz, Santa Cruz, CA 95064, USA. 40School of Elect, PCAWG novel somatic mutation calling methods working group: Matthew H. Bailey1,2,3, Beifang Niu35, Matthias Bieg42,43, Paul C. Boutros6,44,45,46, Ivo Buchhalter43,47,48, Adam P. Butler49, Ken Chen50, Zechen Chong51, Li Ding1,2,3,20, Oliver Drechsel52,53, Lewis Jonathan Dursi6,7, Roland Eils47,48,54,55, Kyle Ellrott9, Shadrielle M. G. Espiritu6, Yu Fan21, Robert S. Fulton1,3,20, Shengjie Gao56, Josep L. l. Gelpi57,58, Mark B. Gerstein5,18,19, Gad Getz8,14,15,16, Santiago Gonzalez59,60, Ivo G. Gut52,61, Faraz Hach62,63, Michael C. Heinold47,48, Julian M. Hess8,26, Jonathan Hinton49, Taobo Hu64, Vincent Huang6, Yi Huang65,66, Barbara Hutter43,67,68, David R. Jones49, Jongsun Jung69, Natalie Jäger47, Hyung-Lae Kim70, Kortine Kleinheinz47,48, Sushant Kumar5,19, Yogesh Kumar64, Christopher M. Lalansingh6, Ignaty Leshchiner8, Ivica Letunic71, Dimitri Livitz8, Eric Z. Ma64, Yosef E. Maruvka8,26,72, R. Jay Mashl1,2, Michael D. McLellan1,3,20, Andrew Menzies49, Ana Milovanovic57, Morten Muhlig Nielsen73, Stephan Ossowski52,53,74, Nagarajan Paramasivam43,47, Jakob Skou Pedersen73,75, Marc D. Perry76,77, Montserrat Puiggròs57, Keiran M. Raine49, Esther Rheinbay8,14,72, Romina Royo57, S. Cenk Sahinalp62,78,79, Gordon Saksena8, Iman Sarrafi62,78, Matthias Schlesner47,80, Jared T. Simpson6,17, Lucy Stebbings49, Chip Stewart8, Miranda D. Stobbe52,61, Jon W. Teague49, Grace Tiao8, David Torrents57,81, Jeremiah A. Wala8,14,82, Jiayin Wang1,40,66, Wenyi Wang21, Sebastian M. Waszak60, Joachim Weischenfeldt60,83,84, Michael C. Wendl1,10,11, Johannes Werner47,85, Zhenggang Wu64, Hong Xue64, Sergei Yakneen60, Takafumi N. Yamaguchi6, Kai Ye40,41, Venkata D. Yellapantula20,86, Christina K. Yung76 & Junjun Zhang76, PCAWG Consortium: Lauri A. Aaltonen87, Federico Abascal49, Adam Abeshouse88, Hiroyuki Aburatani89, David J. Adams49, Nishant Agrawal90, Keun Soo Ahn91, Sung-Min Ahn92, Hiroshi Aikata93, Rehan Akbani21, Kadir C. Akdemir50, Hikmat Al-Ahmadie88, Sultan T. Al-Sedairy94, Fatima Al-Shahrour95, Malik Alawi96,97, Monique Albert98, Kenneth Aldape99,100, Ludmil B. Alexandrov49,101,102, Adrian Ally30, Kathryn Alsop103, Eva G. Alvarez104,105,106, Fernanda Amary107, Samirkumar B. Amin108,109,110, Brice Aminou76, Ole Ammerpohl111,112, Matthew J. Anderson113, Yeng Ang114, Davide Antonello115, Pavana Anur22, Samuel Aparicio116, Elizabeth L. Appelbaum1,117, Yasuhito Arai118, Axel Aretz119, Koji Arihiro93, Shun-ichi Ariizumi120, Joshua Armenia121, Laurent Arnould122, Sylvia Asa123,124, Yassen Assenov125, Gurnit Atwal6,126,127, Sietse Aukema112,128, J. Todd Auman129, Miriam R. Aure130, Philip Awadalla6,126, Marta Aymerich131, Gary D. Bader126, Adrian Baez-Ortega132, Matthew H. Bailey1,2,3, Peter J. Bailey133, Miruna Balasundaram30, Saianand Balu134, Pratiti Bandopadhayay8,135,136, Rosamonde E. Banks137, Stefano Barbi138, Andrew P. Barbour139,140, Jonathan Barenboim6, Jill Barnholtz-Sloan141,142, Hugh Barr143, Elisabet Barrera59, John Bartlett98,144, Javier Bartolome57, Claudio Bassi115, Oliver F. Bathe145,146, Daniel Baumhoer147, Prashant Bavi148, Stephen B. Baylin149,150, Wojciech Bazant59, Duncan Beardsmore151, Timothy A. Beck152,153, Sam Behjati49, Andreas Behren154, Beifang Niu35, Cindy Bell155, Sergi Beltran52,61, Christopher Benz156, Andrew Berchuck157, Anke K. Bergmann158, Erik N. Bergstrom101,102, Benjamin P. Berman159,160,161, Daniel M. Berney162, Stephan H. Bernhart163,164,165, Rameen Beroukhim8,14,82, Mario Berrios166, Samantha Bersani167, Johanna Bertl73,168, Miguel Betancourt169, Vinayak Bhandari6,44, Shriram G. Bhosle49, Andrew V. Biankin133,170,171,172, Matthias Bieg42,43, Darell Bigner173, Hans Binder163,164, Ewan Birney59, Michael Birrer72, Nidhan K. Biswas174, Bodil Bjerkehagen147,175, Tom Bodenheimer134, Lori Boice176, Giada Bonizzato177, Johann S. De Bono178, Arnoud Boot179,180, Moiz S. Bootwalla166, Ake Borg181, Arndt Borkhardt182, Keith A. Boroevich183,184, Ivan Borozan6, Christoph Borst185, Marcus Bosenberg186, Mattia Bosio52,53,57, Jacqueline Boultwood187, Guillaume Bourque188,189, Paul C. Boutros6,44,45,46, G. Steven Bova190, David T. Bowen49,191, Reanne Bowlby30, David D. L. Bowtell103, Sandrine Boyault192, Rich Boyce59, Jeffrey Boyd193, Alvis Brazma59, Paul Brennan194, Daniel S. Brewer195,196, Arie B. Brinkman197, Robert G. Bristow44,198,199,200,201, Russell R. Broaddus99, Jane E. Brock202, Malcolm Brock203, Annegien Broeks204, Angela N. Brooks8,24,37,82, Denise Brooks30, Benedikt Brors67,205,206, Søren Brunak207,208, Timothy J. C. Bruxner113,209, Alicia L. Bruzos104,105,106, Alex Buchanan9, Ivo Buchhalter43,47,48, Christiane Buchholz210, Susan Bullman8,82, Hazel Burke211, Birgit Burkhardt212, Kathleen H. Burns213,214, John Busanovich8,215, Carlos D. Bustamante216,217, Adam P. Butler49, Atul J. Butte218, Niall J. Byrne76, Anne-Lise Børresen-Dale130,219, Samantha J. Caesar-Johnson220, Andy Cafferkey59, Declan Cahill221, Claudia Calabrese59,60, Carlos Caldas222,223, Fabien Calvo224, Niedzica Camacho178, Peter J. Campbell49,225, Elias Campo226,227, Cinzia Cantù177, Shaolong Cao21, Thomas E. Carey228, Joana Carlevaro-Fita229,230,231, Rebecca Carlsen30, Ivana Cataldo167,177, Mario Cazzola232, Jonathan Cebon154, Robert Cerfolio233, Dianne E. Chadwick234, Dimple Chakravarty235, Don Chalmers236, Calvin Wing Yiu Chan47,237, Kin Chan238, Michelle Chan-Seng-Yue148, Vishal S. Chandan239, David K. Chang133,170, Stephen J. Chanock240, Lorraine A. Chantrill170,241, Aurélien Chateigner76,242, Nilanjan Chatterjee149,243, Kazuaki Chayama93, Hsiao-Wei Chen114,121, Jieming Chen218, Ken Chen50, Yiwen Chen21, Zhaohong Chen244, Andrew D. Cherniack8,82, Jeremy Chien245, Yoke-Eng Chiew246,247, Suet-Feung Chin222,223, Juok Cho8, Sunghoon Cho248, Jung Kyoon Choi249, Wan Choi250, Christine Chomienne251, Zechen Chong51, Su Pin Choo252, Angela Chou170,246, Angelika N. Christ113, Elizabeth L. Christie103, Eric Chuah30, Carrie Cibulskis8, Kristian Cibulskis8, Sara Cingarlini253, Peter Clapham49, Alexander Claviez254, Sean Cleary148,255, Nicole Cloonan256, Marek Cmero257,258,259, Colin C. Collins62, Ashton A. Connor255,260, Susanna L. Cooke133, Colin S. Cooper178,196,261, Leslie Cope149, Vincenzo Corbo138,177, Matthew G. Cordes1,262, Stephen M. Cordner263, Isidro Cortés-Ciriano264,265,266, Kyle Covington12,23, Prue A. Cowin267, Brian Craft24, David Craft8,268, Chad J. Creighton269, Yupeng Cun270, Erin Curley271, Ioana Cutcutache179,180, Karolina Czajka272, Bogdan Czerniak99,273, Rebecca A. Dagg274, Ludmila Danilova149, Maria Vittoria Davi275, Natalie R. Davidson276,277,278,279,280, Helen Davies49,281,282, Ian J. Davis283, Brandi N. Davis-Dusenbery284, Kevin J. Dawson49, Francisco M. De La Vega216,217,285, Ricardo De Paoli-Iseppi211, Timothy Defreitas8, Angelo P. Dei Tos286, Olivier Delaneau287,288,289, John A. Demchok220, Jonas Demeulemeester290,291, German M. Demidov52,53,74, Deniz Demircioğlu292,293, Nening M. Dennis221, Robert E. Denroche148, Stefan C. Dentro49,290,294, Nikita Desai76, Vikram Deshpande72, Amit G. Deshwar295, Christine Desmedt296,297, Jordi Deu-Pons298,299, Noreen Dhalla30, Neesha C. Dhani300, Priyanka Dhingra301,302, Rajiv Dhir303, Anthony DiBiase304, Klev Diamanti305, Li Ding1,2,3,20, Shuai Ding306, Huy Q. Dinh159, Luc Dirix307, HarshaVardhan Doddapaneni12, Nilgun Donmez62,78, Michelle T. Dow244, Ronny Drapkin308, Oliver Drechsel52,53, Ruben M. Drews223, Serge Serge49, Tim Dudderidge150,221, Ana Dueso-Barroso57, Andrew J. Dunford8, Michael Dunn309, Lewis Jonathan Dursi6,7, Fraser R. Duthie133,310, Ken Dutton-Regester311, Jenna Eagles272, Douglas F. Easton312,313, Stuart Edmonds314, Paul A. Edwards223,315, Sandra E. Edwards178, Rosalind A. Eeles178,221, Anna Ehinger316, Juergen Eils54,55, Roland Eils47,48,54,55, Adel El-Naggar99,273, Matthew Eldridge223, Kyle Ellrott9, Serap Erkek60, Georgia Escaramis53,317,318, Shadrielle M. G. Espiritu6, Xavier Estivill53,319, Dariush Etemadmoghadam103, Jorunn E. Eyfjord320, Bishoy M. Faltas280, Daiming Fan321, Yu Fan21, William C. Faquin72, Claudiu Farcas244, Matteo Fassan322, Aquila Fatima323, Francesco Favero324, Nodirjon Fayzullaev76, Ina Felau220, Sian Fereday103, Martin L. Ferguson325, Vincent Ferretti76,326, Lars Feuerbach205, Matthew A. Field327, J. Lynn Fink57,113, Gaetano Finocchiaro328, Cyril Fisher221, Matthew W. Fittall290, Anna Fitzgerald329, Rebecca C. Fitzgerald282, Adrienne M. Flanagan330, Neil E. Fleshner331, Paul Flicek59, John A. Foekens332, Kwun M. Fong333, Nuno A. Fonseca59,334, Christopher S. Foster335,336, Natalie S. Fox6, Michael Fraser6, Scott Frazer8, Milana Frenkel-Morgenstern337, William Friedman338, Joan Frigola298, Catrina C. Fronick1,262, Akihiro Fujimoto184, Masashi Fujita184, Masashi Fukayama339, Lucinda A. Fulton1 , Robert S. Fulton1,3,20, Mayuko Furuta184, P. Andrew Futreal340, Anja Füllgrabe59, Stacey B. Gabriel8, Steven Gallinger148,255,260, Carlo Gambacorti-Passerini341, Jianjiong Gao121, Shengjie Gao56, Levi Garraway82, Øystein Garred342, Erik Garrison49, Dale W. Garsed103, Nils Gehlenborg8,343, Josep L. l. Gelpi57,58, Joshy George110, Daniela S. Gerhard344, Clarissa Gerhauser345, Jeffrey E. Gershenwald346,347, Mark B. Gerstein5,18,19, Moritz Gerstung59,60, Gad Getz8,14,15,16, Mohammed Ghori49, Ronald Ghossein348, Nasra H. Giama349, Richard A. Gibbs12, Anthony J. Gill170,350, Pelvender Gill351, Dilip D. Giri348, Dominik Glodzik49, Vincent J. Gnanapragasam352,353, Maria Elisabeth Goebler354, Mary J. Goldman24, Carmen Gomez355, Santiago Gonzalez59,60, Abel Gonzalez-Perez298,299,356, Dmitry A. Gordenin357, James Gossage358, Kunihito Gotoh359, Ramaswamy Govindan3, Dorthe Grabau360, Janet S. Graham133,361, Robert C. Grant148,260, Anthony R. Green315, Eric Green27, Liliana Greger59, Nicola Grehan282, Sonia Grimaldi177, Sean M. Grimmond362, Robert L. Grossman363, Adam Grundhoff97,364, Gunes Gundem88, Qianyun Guo75, Manaswi Gupta8, Shailja Gupta365, Ivo G. Gut52,61, Marta Gut52,61, Jonathan Göke292,366, Gavin Ha8, Andrea Haake111, David Haan37, Siegfried Haas185, Kerstin Haase290, James E. Haber367, Nina Habermann60, Faraz Hach62,63, Syed Haider6, Natsuko Hama118, Freddie C. Hamdy351, Anne Hamilton267, Mark P. Hamilton368, Leng Han369, George B. Hanna370, Martin Hansmann371, Nicholas J. Haradhvala8,72, Olivier Harismendy102,372, Ivon Harliwong113, Arif O. Harmanci5,373, Eoghan Harrington374, Takanori Hasegawa375, David Haussler24,25, Steve Hawkins223, Shinya Hayami376, Shuto Hayashi375, D. Neil Hayes134,377,378, Stephen J. Hayes379,380, Nicholas K. Hayward211,311, Steven Hazell221, Yao He381, Allison P. Heath382, Simon C. Heath52,61, David Hedley300, Apurva M. Hegde38, David I. Heiman8, Michael C. Heinold47,48, Zachary Heins88, Lawrence E. Heisler152, Eva Hellstrom-Lindberg383, Mohamed Helmy384, Seong Gu Heo385, Austin J. Hepperla134, José María Heredia-Genestar386, Carl Herrmann47,48,387, Peter Hersey211, Julian M. Hess8,26, Holmfridur Hilmarsdottir320, Jonathan Hinton49, Satoshi Hirano388, Nobuyoshi Hiraoka389, Katherine A. Hoadley134,390, Asger Hobolth75,168, Ermin Hodzic78, Jessica I. Hoell182, Steve Hoffmann163,164,165,391, Oliver Hofmann392, Andrea Holbrook166, Aliaksei Z. Holik53, Michael A. Hollingsworth393, Oliver Holmes209,311, Robert A. Holt30, Chen Hong205,237, Eun Pyo Hong385, Jongwhi H. Hong394, Gerrit K. Hooijer395, Henrik Hornshøj73, Fumie Hosoda118, Yong Hou56,396, Volker Hovestadt397, William Howat352, Alan P. Hoyle134, Ralph H. Hruban149, Jianhong Hu12, Taobo Hu64, Xing Hua240, Kuan-lin Huang1,398, Mei Huang176, Mi Ni Huang179,180, Vincent Huang6, Yi Huang65,66, Wolfgang Huber60, Thomas J. Hudson272,399, Michael Hummel400, Jillian A. Hung246,247, David Huntsman401, Ted R. Hupp402, Jason Huse88, Matthew R. Huska403, Barbara Hutter43,67,68, Carolyn M. Hutter27, Daniel Hübschmann48,54,404,405,406, Christine A. Iacobuzio-Donahue348, Charles David Imbusch205, Marcin Imielinski407,408, Seiya Imoto375, William B. Isaacs409, Keren Isaev6,44, Shumpei Ishikawa410, Murat Iskar397, S. M. Ashiqul Islam244, Michael Ittmann411,412,413, Sinisa Ivkovic284, Jose M. G. Izarzugaza414, Jocelyne Jacquemier415, Valerie Jakrot211, Nigel B. Jamieson133,172,416, Gun Ho Jang148, Se Jin Jang417, Joy C. Jayaseelan12, Reyka Jayasinghe1 , Stuart R. Jefferys134, Karine Jegalian418, Jennifer L. Jennings419, Seung-Hyup Jeon250, Lara Jerman60,420, Yuan Ji421,422, Wei Jiao6, Peter A. Johansson311, Amber L. Johns170, Jeremy Johns272, Rory Johnson230,423, Todd A. Johnson183, Clemency Jolly290, Yann Joly424, Jon G. Jonasson320, Corbin D. Jones425, David R. Jones49, David T. W. Jones426,427, Nic Jones428, Steven J. M. Jones30, Jos Jonkers204, Young Seok Ju49,249, Hartmut Juhl429, Jongsun Jung69, Malene Juul73, Randi Istrup Juul73, Sissel Juul374, Natalie Jäger47, Rolf Kabbe47, Andre Kahles276,277,278,279,430, Abdullah Kahraman431,432,433, Vera B. Kaiser434, Hojabr Kakavand211, Sangeetha Kalimuthu148, Christof von Kalle405, Koo Jeong Kang91, Katalin Karaszi351, Beth Karlan435, Rosa Karlić436, Dennis Karsch437, Katayoon Kasaian29,30, Karin S. Kassahn113,438, Hitoshi Katai439, Mamoru Kato440, Hiroto Katoh410, Yoshiiku Kawakami93, Jonathan D. Kay117, Stephen H. Kazakoff209,311, Marat D. Kazanov441,442,443, Maria Keays59, Electron Kebebew444,445, Richard F. Kefford446, Manolis Kellis8,447, James G. Kench170,350,448, Catherine J. Kennedy246,247, Jules N. A. Kerssemakers47, David Khoo273, Vincent Khoo221, Narong Khuntikeo115,449, Ekta Khurana301,302,450,451, Helena Kilpinen117, Hark Kyun Kim452, Hyung-Lae Kim70, Hyung-Yong Kim415, Hyunghwan Kim250, Jaegil Kim8, Jihoon Kim453, Jong K. Kim454, Youngwook Kim455,456, Tari A. King457,458,459, Wolfram Klapper128, Kortine Kleinheinz47,48, Leszek J. Klimczak460, Stian Knappskog49,461, Michael Kneba437, Bartha M. Knoppers424, Youngil Koh462,463, Jan Komorowski305,464, Daisuke Komura410, Mitsuhiro Komura375, Gu Kong415, Marcel Kool426,465, Jan O. Korbel59,60, Viktoriya Korchina12, Andrey Korshunov465, Michael Koscher465, Roelof Koster466, Zsofia Kote-Jarai178, Antonios Koures244, Milena Kovacevic284, Barbara Kremeyer49, Helene Kretzmer164,165, Markus Kreuz467, Savitri Krishnamurthy99,468, Dieter Kube469, Kiran Kumar8, Pardeep Kumar221, Sushant Kumar5,19, Yogesh Kumar64, Ritika Kundra114,121, Kirsten Kübler8,14,72, Ralf Küppers470, Jesper Lagergren383,471, Phillip H. Lai166, Peter W. Laird472, Sunil R. Lakhani473, Christopher M. Lalansingh6, Emilie Lalonde6, Fabien C. Lamaze6, Adam Lambert351, Eric Lander8, Pablo Landgraf474,475, Luca Landoni115, Anita Langerød130, Andrés Lanzós230,231,423, Denis Larsimont476, Erik Larsson477, Mark Lathrop189, Loretta M. S. Lau478, Chris Lawerenz55, Rita T. Lawlor177, Michael S. Lawrence8,72,183, Alexander J. Lazar99,108, Xuan Le479, Darlene Lee30, Donghoon Lee5, Eunjung Alice Lee480, Hee Jin Lee417, Jake June-Koo Lee264,266, Jeong-Yeon Lee481, Juhee Lee482, Ming Ta Michael Lee340, Henry Lee-Six49, Kjong-Van Lehmann276,277,278,279,430, Hans Lehrach483, Dido Lenze400, Conrad R. Leonard209,311, Daniel A. Leongamornlert49,178, Ignaty Leshchiner8, Louis Letourneau484, Ivica Letunic71, Douglas A. Levine88,485, Lora Lewis12, Tim Ley486, Chang Li56,396, Constance H. Li6,44, Haiyan Irene Li30, Jun Li21, Lin Li56, Shantao Li5, Siliang Li56,396, Xiaobo Li56,396, Xiaotong Li5, Xinyue Li56, Yilong Li49, Han Liang21, Sheng-Ben Liang234, Peter Lichter68,397, Pei Lin8, Ziao Lin8,487, W. M. Linehan488, Ole Christian Lingjærde489, Dongbing Liu56,396, Eric Minwei Liu88,301,302, Fei-Fei Liu201,490, Fenglin Liu381,491, Jia Liu492, Xingmin Liu56,396, Julie Livingstone6, Dimitri Livitz8, Naomi Livni221, Lucas Lochovsky5,19,110, Markus Loeffler467, Georgina V. Long211, Armando Lopez-Guillermo493, Shaoke Lou5,19, David N. Louis72, Laurence B. Lovat117, Yiling Lu38, Yong-Jie Lu162,494, Youyong Lu495,496,497, Claudio Luchini167, Ilinca Lungu144,148, Xuemei Luo152, Hayley J. Luxton117, Andy G. Lynch223,315,498, Lisa Lype36, Cristina López111,112, Carlos López-Otín499, Eric Z. Ma64, Yussanne Ma30, Gaetan MacGrogan500, Shona MacRae501, Geoff Macintyre223, Tobias Madsen73, Kazuhiro Maejima184, Andrea Mafficini177, Dennis T. Maglinte166,502, Arindam Maitra174, Partha P. Majumder174, Luca Malcovati232, Salem Malikic62,78, Giuseppe Malleo115, Graham J. Mann211,246,503, Luisa Mantovani-Löffler504, Kathleen Marchal505,506, Giovanni Marchegiani115, Elaine R. Mardis1,193,507, Adam A. Margolin31, Maximillian G. Marin37, Florian Markowetz223,315, Julia Markowski403, Jeffrey Marks508, Tomas Marques-Bonet61,81,386,509, Marco A. Marra30, Luke Marsden351, John W. M. Martens332, Sancha Martin49,510, Jose I. Martin-Subero81,511, Iñigo Martincorena49, Alexander Martinez-Fundichely301,302,451 Yosef E. Maruvka8,26,72, R. Jay Mashl1,2, Charlie E. Massie223, Thomas J. Matthew37, Lucy Matthews178, Erik Mayer221,512, Simon Mayes513, Michael Mayo30, Faridah Mbabaali272, Karen McCune514, Ultan McDermott49, Patrick D. McGillivray19, Michael D. McLellan1,3,20, John D. McPherson148,272,515, John R. McPherson179,180, Treasa A. McPherson260, Samuel R. Meier8, Alice Meng516, Shaowu Meng134, Andrew Menzies49, Neil D. Merrett115,517, Sue Merson178, Matthew Meyerson8,14,82, William U. Meyerson4,5, Piotr A. Mieczkowski518, George L. Mihaiescu76, Sanja Mijalkovic284, Ana Mijalkovic Mijalkovic-Lazic284, Tom Mikkelsen519, Michele Milella253, Linda Mileshkin103, Christopher A. Miller1 , David K. Miller113,170, Jessica K. Miller272, Gordon B. Mills33,34, Ana Milovanovic57, Sarah Minner520, Marco Miotto115, Gisela Mir Arnau267, Lisa Mirabello240, Chris Mitchell103, Thomas J. Mitchell49,315,352, Satoru Miyano375, Naoki Miyoshi375, Shinichi Mizuno521, Fruzsina Molnár-Gábor522, Malcolm J. Moore300, Richard A. Moore30, Sandro Morganella49, Quaid D. Morris127,490, Carl Morrison523,524, Lisle E. Mose134, Catherine D. Moser349, Ferran Muiños298,299, Loris Mularoni298,299, Andrew J. Mungall30, Karen Mungall30, Elizabeth A. Musgrove133, Ville Mustonen525,526,527, David Mutch528, Francesc Muyas52,53,74, Donna M. Muzny12, Alfonso Muñoz59, Jerome Myers529, Ola Myklebost461, Peter Möller530, Genta Nagae89, Adnan M. Nagrial170, Hardeep K. Nahal-Bose76, Hitoshi Nakagama531, Hidewaki Nakagawa184, Hiromi Nakamura118, Toru Nakamura388, Kaoru Nakano184, Tannistha Nandi532, Jyoti Nangalia49, Mia Nastic284, Arcadi Navarro61,81,386, Fabio C. P. Navarro19, David E. Neal223,352, Gerd Nettekoven533, Felicity Newell209,311, Steven J. Newhouse59, Yulia Newton37, Alvin Wei Tian Ng534, Anthony Ng535, Jonathan Nicholson49, David Nicol221, Yongzhan Nie321,536, G. Petur Nielsen72, Morten Muhlig Nielsen73, Serena Nik-Zainal49,281,282,537, Michael S. Noble8, Katia Nones209,311, Paul A. Northcott538, Faiyaz Notta148,539, Brian D. O’Connor76,540, Peter O’Donnell541, Maria O’Donovan282, Sarah O’Meara49, Brian Patrick O’Neill542, J. Robert O’Neill543, David Ocana59, Angelica Ochoa88, Layla Oesper544, Christopher Ogden221, Hideki Ohdan93, Kazuhiro Ohi375, Lucila Ohno-Machado244, Karin A. Oien523,545, Akinyemi I. Ojesina546,547,548, Hidenori Ojima549, Takuji Okusaka550, Larsson Omberg551, Choon Kiat Ong552, Stephan Ossowski52,53,74, German Ott553, B. F. Francis Ouellette76,554, Christine P’ng6, Marta Paczkowska6, Salvatore Paiella115, Chawalit Pairojkul523, Marina Pajic170, Qiang Pan-Hammarström56,555, Elli Papaemmanuil49, Irene Papatheodorou59, Nagarajan Paramasivam43,47, Ji Wan Park385, Joong-Won Park556, Keunchil Park557,558, Kiejung Park559, Peter J. Park264,266, Joel S. Parker518, Simon L. Parsons124, Harvey Pass560, Danielle Pasternack272, Alessandro Pastore276, Ann-Marie Patch209,311, Iris Pauporté251, Antonio Pea115, John V. Pearson209,311, Chandra Sekhar Pedamallu8,14,82, Jakob Skou Pedersen73,75, Paolo Pederzoli115, Martin Peifer270, Nathan A. Pennell561, Charles M. Perou129,518, Marc D. Perry76,77, Gloria M. Petersen562, Myron Peto22, Nicholas Petrelli563, Robert Petryszak59, Stefan M. Pfister426,465,564, Mark Phillips424, Oriol Pich298,299, Hilda A. Pickett478, Todd D. Pihl565, Nischalan Pillay566, Sarah Pinder567, Mark Pinese170, Andreia V. Pinho568, Esa Pitkänen60, Xavier Pivot569, Elena Piñeiro-Yáñez95, Laura Planko533, Christoph Plass345, Paz Polak8,14,15, Tirso Pons570, Irinel Popescu571, Olga Potapova572, Aparna Prasad52, Shaun R. Preston573, Manuel Prinz47, Antonia L. Pritchard311, Stephenie D. Prokopec6, Elena Provenzano574, Xose S. Puente499, Sonia Puig176, Montserrat Puiggròs57, Sergio Pulido-Tamayo505,506, Gulietta M. Pupo246, Colin A. Purdie575, Michael C. Quinn209,311, Raquel Rabionet52,53,576, Janet S. Rader577, Bernhard Radlwimmer397, Petar Radovic284, Benjamin Raeder60, Keiran M. Raine49, Manasa Ramakrishna49, Kamna Ramakrishnan49, Suresh Ramalingam578, Benjamin J. Raphael579, W. Kimryn Rathmell580, Tobias Rausch60, Guido Reifenberger475, Jüri Reimand6,44, Jorge Reis-Filho348, Victor Reuter348, Iker Reyes-Salazar298, Matthew A. Reyna579, Sheila M. Reynolds36, Esther Rheinbay8,14,72, Yasser Riazalhosseini189, Andrea L. Richardson323, Julia Richter111,128, Matthew Ringel581, Markus Ringnér181, Yasushi Rino582, Karsten Rippe405, Jeffrey Roach583, Lewis R. Roberts349, Nicola D. Roberts49, Steven A. Roberts584, A. Gordon Robertson30, Alan J. Robertson113, Javier Bartolomé Rodriguez57, Bernardo Rodriguez-Martin104,105,106, F. Germán Rodríguez-González83,332, Michael H. A. Roehrl44,123,148,234,585,586, Marius Rohde587, Hirofumi Rokutan440, Gilles Romieu588, Ilse Rooman170, Tom Roques262, Daniel Rosebrock8, Mara Rosenberg8,72, Philip C. Rosenstiel589, Andreas Rosenwald590, Edward W. Rowe221,591, Romina Royo57, Steven G. Rozen179,180,592, Yulia Rubanova17,127, Mark A. Rubin423,593,594,595,596, Carlota Rubio-Perez298,299,597, Vasilisa A. Rudneva60, Borislav C. Rusev177, Andrea Ruzzenente598, Gunnar Rätsch276,277,278,279,280,430, Radhakrishnan Sabarinathan298,299,599, Veronica Y. Sabelnykova6, Sara Sadeghi30, S. Cenk Sahinalp62,78,79, Natalie Saini357, Mihoko Saito-Adachi440, Gordon Saksena8, Adriana Salcedo6, Roberto Salgado600, Leonidas Salichos5,19, Richard Sallari8, Charles Saller601, Roberto Salvia115, Michelle Sam272, Jaswinder S. Samra115,602, Francisco Sanchez-Vega114,121, Chris Sander276,603,604, Grant Sanders134, Rajiv Sarin605, Iman Sarrafi62,78, Aya Sasaki-Oku184, Torill Sauer489, Guido Sauter520, Robyn P. M. Saw211, Maria Scardoni167, Christopher J. Scarlett170,606, Aldo Scarpa177, Ghislaine Scelo194, Dirk Schadendorf68,607, Jacqueline E. Schein30, Markus B. Schilhabel589, Matthias Schlesner47,80, Thorsten Schlomm84,608, Heather K. Schmidt1 , Sarah-Jane Schramm246, Stefan Schreiber609, Nikolaus Schultz121, Steven E. Schumacher8,323, Roland F. Schwarz59,403,405,610, Richard A. Scolyer211,448,602, David Scott428, Ralph Scully611, Raja Seethala612, Ayellet V. Segre8,613, Iris Selander260, Colin A. Semple434, Yasin Senbabaoglu276, Subhajit Sengupta614, Elisabetta Sereni115, Stefano Serra585, Dennis C. Sgroi72, Mark Shackleton103, Nimish C. Shah352, Sagedeh Shahabi234, Catherine A. Shang329, Ping Shang211, Ofer Shapira8,323, Troy Shelton271, Ciyue Shen603,604, Hui Shen615, Rebecca Shepherd49, Ruian Shi490, Yan Shi134, Yu-Jia Shiah6, Tatsuhiro Shibata118,616, Juliann Shih8,82, Eigo Shimizu375, Kiyo Shimizu617, Seung Jun Shin618, Yuichi Shiraishi375, Tal Shmaya285, Ilya Shmulevich36, Solomon I. Shorser6, Charles Short59, Raunak Shrestha62, Suyash S. Shringarpure217, Craig Shriver619, Shimin Shuai6,126, Nikos Sidiropoulos83, Reiner Siebert112,620, Anieta M. Sieuwerts332, Lina Sieverling205,237, Sabina Signoretti202,621, Katarzyna O. Sikora177, Michele Simbolo138, Ronald Simon520, Janae V. Simons134, Jared T. Simpson6,17, Peter T. Simpson473, Samuel Singer115,458, Nasa Sinnott-Armstrong8,217, Payal Sipahimalani30, Tara J. Skelly390, Marcel Smid332, Jaclyn Smith622, Karen Smith-McCune514, Nicholas D. Socci276, Heidi J. Sofia27, Matthew G. Soloway134, Lei Song240, Anil K. Sood623,624,625, Sharmila Sothi626, Christos Sotiriou244, Cameron M. Soulette37, Paul N. Span627, Paul T. Spellman22, Nicola Sperandio177, Andrew J. Spillane211, Oliver Spiro8, Jonathan Spring628, Johan Staaf181, Peter F. Stadler163,164,165, Peter Staib629, Stefan G. Stark277,279,618,630, Lucy Stebbings49, Ólafur Andri Stefánsson631, Oliver Stegle59,60,632, Lincoln D. Stein6,126, Alasdair Stenhouse633, Chip Stewart8, Stephan Stilgenbauer634, Miranda D. Stobbe52,61, Michael R. Stratton49, Jonathan R. Stretch211, Adam J. Struck31, Joshua M. Stuart24,37, Henk G. Stunnenberg396,635, Hong Su56,396, Xiaoping Su99, Ren X. Sun6, Stephanie Sungalee60, Hana Susak52,53, Akihiro Suzuki89,636, Fred Sweep637, Monika Szczepanowski128, Holger Sültmann67,638, Takashi Yugawa617, Angela Tam30, David Tamborero298,299, Benita Kiat Tee Tan639, Donghui Tan518, Patrick Tan180,532,592,640, Hiroko Tanaka375, Hirokazu Taniguchi616, Tomas J. Tanskanen641, Maxime Tarabichi49,290, Roy Tarnuzzer220, Patrick Tarpey642, Morgan L. Taschuk152, Kenji Tatsuno89, Simon Tavaré223,643, Darrin F. Taylor113, Amaro Taylor-Weiner8, Jon W. Teague49, Bin Tean Teh180,592,640,644,645, Varsha Tembe246, Javier Temes104,105, Kevin Thai76, Sarah P. Thayer393, Nina Thiessen30, Gilles Thomas646, Sarah Thomas221, Alan Thompson221, Alastair M. Thompson633, John F. Thompson211, R. Houston Thompson647, Heather Thorne103, Leigh B. Thorne176, Adrian Thorogood424, Grace Tiao8, Nebojsa Tijanic284, Lee E. Timms272, Roberto Tirabosco648, Marta Tojo106, Stefania Tommasi649, Christopher W. Toon170, Umut H. Toprak48,650, David Torrents57,81, Giampaolo Tortora651,652, Jörg Tost653, Yasushi Totoki118, David Townend654, Nadia Traficante103, Isabelle Treilleux655,656, Jean-Rémi Trotta61, Lorenz H. P. Trümper469, Ming Tsao124,539, Tatsuhiko Tsunoda183,657,658,659, Jose M. C. Tubio104,105,106, Olga Tucker660, Richard Turkington661, Daniel J. Turner513, Andrew Tutt323, Masaki Ueno376, Naoto T. Ueno662, Christopher Umbricht151,213,663, Husen M. Umer305,664, Timothy J. Underwood665, Lara Urban59,60, Tomoko Urushidate616, Tetsuo Ushiku339, Liis Uusküla-Reimand666,667, Alfonso Valencia57,81, David J. Van Den Berg166, Steven Van Laere307, Peter Van Loo290,291, Erwin G. Van Meir668, Gert G. Van den Eynden307, Theodorus Van der Kwast123, Naveen Vasudev137, Miguel Vazquez57,669, Ravikiran Vedururu267, Umadevi Veluvolu518, Shankar Vembu490,670, Lieven P. C. Verbeke506,671, Peter Vermeulen307, Clare Verrill351,672, Alain Viari177, David Vicente57, Caterina Vicentini177, K. Vijay Raghavan365, Juris Viksna673, Ricardo E. Vilain674, Izar Villasante57, Anne Vincent-Salomon635, Tapio Visakorpi190, Douglas Voet8, Paresh Vyas311,351, Ignacio Vázquez-García49,86,675,676, Nick M. Waddell209, Nicola Waddell209,311, Claes Wadelius677, Lina Wadi6, Rabea Wagener111,112, Jeremiah A. Wala8,14,82, Jian Wang56, Jiayin Wang1,40,66, Linghua Wang12, Qi Wang465, Wenyi Wang21, Yumeng Wang21, Zhining Wang220, Paul M. Waring523, Hans-Jörg Warnatz483, Jonathan Warrell5,19, Anne Y. Warren352,678, Sebastian M. Waszak60, David C. Wedge49,294,679, Dieter Weichenhan345, Paul Weinberger680, John N. Weinstein38, Joachim Weischenfeldt60,83,84, Daniel J. Weisenberger166, Ian Welch681, Michael C. Wendl1,10,11, Johannes Werner47,85, Justin P. Whalley61,682, David A. Wheeler12,13, Hayley C. Whitaker117, Dennis Wigle683, Matthew D. Wilkerson518, Ashley Williams244, James S. Wilmott211, Gavin W. Wilson6,148, Julie M. Wilson148, Richard K. Wilson1,684, Boris Winterhoff685, Jeffrey A. Wintersinger17,127,384, Maciej Wiznerowicz686,687, Stephan Wolf688, Bernice H. Wong689, Tina Wong1,30, Winghing Wong690, Youngchoon Woo250, Scott Wood209,311, Bradly G. Wouters44, Adam J. Wright6, Derek W. Wright133,691, Mark H. Wright217, Chin-Lee Wu72, Dai-Ying Wu285, Guanming Wu692, Jianmin Wu170, Kui Wu56,396, Yang Wu179,180, Zhenggang Wu64, Liu Xi12, Tian Xia693, Qian Xiang76, Xiao Xiao66, Rui Xing497, Heng Xiong56,396, Qinying Xu209,311, Yanxun Xu694, Hong Xue64, Shinichi Yachida118,695, Sergei Yakneen60, Rui Yamaguchi375, Takafumi N. Yamaguchi6, Masakazu Yamamoto120, Shogo Yamamoto89, Hiroki Yamaue376, Fan Yang490, Huanming Yang56, Jean Y. Yang696, Liming Yang220, Lixing Yang697, Shanlin Yang306, Tsun-Po Yang270, Yang Yang369, Xiaotong Yao408,698, Marie-Laure Yaspo483, Lucy Yates49, Christina Yau156, Chen Ye56,396, Kai Ye40,41, Venkata D. Yellapantula20,86, Christopher J. Yoon249, Sung-Soo Yoon463, Fouad Yousif6, Jun Yu699, Kaixian Yu700, Willie Yu701, Yingyan Yu702, Ke Yuan223,510,703, Yuan Yuan21, Denis Yuen6, Takashi Yugawa617, Christina K. Yung76, Olga Zaikova704, Jorge Zamora49,104,105,106, Marc Zapatka397, Jean C. Zenklusen220, Thorsten Zenz67, Nikolajs Zeps705,706, Cheng-Zhong Zhang8,707, Fan Zhang381, Hailei Zhang8, Hongwei Zhang494, Hongxin Zhang121, Jiashan Zhang220, Jing Zhang5, Junjun Zhang76, Xiuqing Zhang56, Xuanping Zhang66,369, Yan Zhang5,708,709, Zemin Zhang381,710, Zhongming Zhao711, Liangtao Zheng381, Xiuqing Zheng381, Wanding Zhou615, Yong Zhou56, Bin Zhu240, Hongtu Zhu700,712, Jingchun Zhu24, Shida Zhu56,396, Lihua Zou713, Xueqing Zou49, Anna deFazio246,247,714, Nicholas van As221, Carolien H. M. van Deurzen715, Marc J. van de Vijver523, L. van’t Veer716 & Christian von Mering433,717, The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts.
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- 2020
32. Linking aberrant chromatin features in chronic lymphocytic leukemia to transcription factor networks
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Sabrina Kugler, Fabian Erdel, Sebastian Großmann, Jose M. Muiño, Daniele Tavernari, Lara Klett, Sandra D Koser, Martin Vingron, Daniel Remondini, Marc Zapatka, Jan-Philipp Mallm, Rainer König, Stephan Stilgenbauer, Peter Lichter, Karsten Rippe, Benedikt Brors, Vladimir B. Teif, Alexandra M Poos, Sabrina Schumacher, Naveed Ishaque, Murat Iskar, Daniel Mertens, Mallm J.-P., Iskar M., Ishaque N., Klett L.C., Kugler S.J., Muino J.M., Teif V.B., Poos A.M., Grossmann S., Erdel F., Tavernari D., Koser S.D., Schumacher S., Brors B., Konig R., Remondini D., Vingron M., Stilgenbauer S., Lichter P., Zapatka M., Mertens D., and Rippe K.
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CCCTC-Binding Factor ,Medicine (General) ,DNS ,Amino Acid Motifs ,gene regulatory network ,Chromatin, Epigenetics, Genomics & Functional Genomics ,Gene regulatory networks ,Histones ,0302 clinical medicine ,hemic and lymphatic diseases ,Biology (General) ,Promoter Regions, Genetic ,Chronisch-lymphatische Leuk��mie ,Cancer ,0303 health sciences ,DNA methylation ,biology ,Gene Expression Regulation, Leukemic ,histone modifications ,Applied Mathematics ,Articles ,Middle Aged ,Chromatin ,3. Good health ,Cell biology ,Enhancer Elements, Genetic ,Histone ,Computational Theory and Mathematics ,Genome-Scale & Integrative Biology ,Chronisch-lymphatische Leukämie ,Histone deacetylase activity ,General Agricultural and Biological Sciences ,Protein Binding ,Information Systems ,QH301-705.5 ,bivalent promoter ,enhancer ,gene regulatory networks ,Down-Regulation ,Article ,Histone Deacetylases ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,R5-920 ,Humans ,Nucleosome ,Epigenetics ,ddc:610 ,Enhancer ,Aged ,030304 developmental biology ,Binding Sites ,General Immunology and Microbiology ,DNA ,Leukemia, Lymphocytic, Chronic, B-Cell ,Methylierung ,CTCF ,Trans-Activators ,biology.protein ,DDC 610 / Medicine & health ,030217 neurology & neurosurgery - Abstract
In chronic lymphocytic leukemia (CLL), a diverse set of genetic mutations is embedded in a deregulated epigenetic landscape that drives cancerogenesis. To elucidate the role of aberrant chromatin features, we mapped DNA methylation, seven histone modifications, nucleosome positions, chromatin accessibility, binding of EBF1 and CTCF, as well as the transcriptome of B cells from CLL patients and healthy donors. A globally increased histone deacetylase activity was detected and half of the genome comprised transcriptionally downregulated partially DNA methylated domains demarcated by CTCF. CLL samples displayed a H3K4me3 redistribution and nucleosome gain at promoters as well as changes of enhancer activity and enhancer linkage to target genes. A DNA binding motif analysis identified transcription factors that gained or lost binding in CLL at sites with aberrant chromatin features. These findings were integrated into a gene regulatory enhancer containing network enriched for B-cell receptor signaling pathway components. Our study predicts novel molecular links to targets of CLL therapies and provides a valuable resource for further studies on the epigenetic contribution to the disease., publishedVersion
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- 2019
33. Processing of mRNA and Quality Control
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Edouard Bertrand, Ute Schmidt, Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), and Rippe, K.
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Non-stop decay ,0303 health sciences ,Messenger RNA ,Chemistry ,Nonsense-mediated decay ,mRNA surveillance ,Cell biology ,Messenger RNP ,03 medical and health sciences ,0302 clinical medicine ,RNA splicing ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,ComputingMilieux_MISCELLANEOUS ,030217 neurology & neurosurgery ,No-go decay ,030304 developmental biology - Abstract
International audience
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- 2011
34. The biological and clinical impact of deletions before and after large chromosomal gains in multiple myeloma.
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Cirrincione AM, Poos AM, Ziccheddu B, Kaddoura M, Bärtsch MA, Maclachlan K, Chojnacka M, Diamond B, John L, Reichert P, Huhn S, Blaney P, Gagler D, Rippe K, Zhang Y, Dogan A, Lesokhin AM, Davies F, Goldschmidt H, Fenk R, Weisel KC, Mai EK, Korde N, Morgan GJ, Usmani S, Landgren O, Raab MS, Weinhold N, and Maura F
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- Humans, Translocation, Genetic, Immunoglobulin Heavy Chains genetics, Chromosome Aberrations, Gene Deletion, Male, Female, Genes, Tumor Suppressor, Multiple Myeloma genetics
- Abstract
Abstract: Acquisition of a hyperdiploid (HY) karyotype or immunoglobulin heavy chain (IgH) translocations are considered key initiating events in multiple myeloma (MM). To explore if other genomic events can precede these events, we analyzed whole-genome sequencing data from 1173 MM samples. By integrating molecular time and structural variants within early chromosomal duplications, we indeed identified pregain deletions in 9.4% of patients with an HY karyotype without IgH translocations, challenging acquisition of an HY karyotype as the earliest somatic event. Remarkably, these deletions affected tumor suppressor genes (TSGs) and/or oncogenes in 2.4% of patients with an HY karyotype without IgH translocations, supporting their role in MM pathogenesis. Furthermore, our study points to postgain deletions as novel driver mechanisms in MM. Using multiomics approaches to investigate their biologic impact, we found associations with poor clinical outcome in newly diagnosed patients and profound effects on both the oncogene and TSG activity despite the diploid gene status. Overall, this study provides novel insights into the temporal dynamics of genomic alterations in MM., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)
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- 2024
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35. T-bet suppresses proliferation of malignant B cells in chronic lymphocytic leukemia.
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Roessner PM, Seufert I, Chapaprieta V, Jayabalan R, Briesch H, Massoni-Badosa R, Boskovic P, Benckendorff J, Roider T, Arseni L, Coelho M, Chakraborty S, Vaca AM, Sivina M, Muckenhuber M, Rodriguez-Rodriguez S, Bonato A, Herbst SA, Zapatka M, Sun C, Kretzmer H, Naake T, Bruch PM, Czernilofsky F, Ten Hacken E, Schneider M, Helm D, Yosifov DY, Kauer J, Danilov AV, Bewarder M, Heyne K, Schneider C, Stilgenbauer S, Wiestner A, Mallm JP, Burger JA, Efremov DG, Lichter P, Dietrich S, Martin-Subero JI, Rippe K, and Seiffert M
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- Animals, Humans, Mice, B-Lymphocytes pathology, B-Lymphocytes metabolism, B-Lymphocytes immunology, Mice, Knockout, Gene Expression Regulation, Leukemic, NF-kappa B metabolism, Leukemia, Lymphocytic, Chronic, B-Cell pathology, Leukemia, Lymphocytic, Chronic, B-Cell genetics, Leukemia, Lymphocytic, Chronic, B-Cell immunology, Leukemia, Lymphocytic, Chronic, B-Cell metabolism, T-Box Domain Proteins genetics, T-Box Domain Proteins metabolism, Cell Proliferation
- Abstract
Abstract: The T-box transcription factor T-bet is known as a master regulator of the T-cell response but its role in malignant B cells has not been sufficiently explored. Here, we conducted single-cell resolved multi-omics analyses of malignant B cells from patients with chronic lymphocytic leukemia (CLL) and studied a CLL mouse model with a genetic knockout of Tbx21. We found that T-bet acts as a tumor suppressor in malignant B cells by decreasing their proliferation rate. NF-κB activity, induced by inflammatory signals provided by the microenvironment, triggered T-bet expression, which affected promoter-proximal and distal chromatin coaccessibility and controlled a specific gene signature by mainly suppressing transcription. Gene set enrichment analysis identified a positive regulation of interferon signaling and negative control of proliferation by T-bet. In line, we showed that T-bet represses cell cycling and is associated with longer overall survival of patients with CLL. Our study uncovered a novel tumor suppressive role of T-bet in malignant B cells via its regulation of inflammatory processes and cell cycling, which has implications for the stratification and therapy of patients with CLL. Linking T-bet activity to inflammation explains the good prognostic role of genetic alterations in the inflammatory signaling pathways in CLL.
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- 2024
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36. The Virtual Child.
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Gilbertson RJ, Behjati S, Böttcher AL, Bronner ME, Burridge M, Clausing H, Clifford H, Danaher T, Donovan LK, Drost J, Eggermont AMM, Emerson C, Flores MG, Hamerlik P, Jabado N, Jones A, Kaessmann H, Kleinman CL, Kool M, Kutscher LM, Lindberg G, Linnane E, Marioni JC, Maris JM, Monje M, Macaskill A, Niederer S, Northcott PA, Peeters E, Plieger-van Solkema W, Preußner L, Rios AC, Rippe K, Sandford P, Sgourakis NG, Shlien A, Smith P, Straathof K, Sullivan PJ, Suvà ML, Taylor MD, Thompson E, Vento-Tormo R, Wainwright BJ, Wechsler-Reya RJ, Westermann F, Winslade S, Al-Lazikani B, and Pfister SM
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- Humans, Neoplasms genetics
- Abstract
Summary: We are building the world's first Virtual Child-a computer model of normal and cancerous human development at the level of each individual cell. The Virtual Child will "develop cancer" that we will subject to unlimited virtual clinical trials that pinpoint, predict, and prioritize potential new treatments, bringing forward the day when no child dies of cancer, giving each one the opportunity to lead a full and healthy life., (©2024 American Association for Cancer Research.)
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- 2024
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37. Evolution of SARS-CoV-2 in the Rhine-Neckar/Heidelberg Region 01/2021 - 07/2023.
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Bundschuh C, Weidner N, Klein J, Rausch T, Azevedo N, Telzerow A, Mallm JP, Kim H, Steiger S, Seufert I, Börner K, Bauer K, Hübschmann D, Jost KL, Parthé S, Schnitzler P, Boutros M, Rippe K, Müller B, Bartenschlager R, Kräusslich HG, and Benes V
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- Humans, Germany epidemiology, Hospitals, University, SARS-CoV-2 genetics, COVID-19 epidemiology
- Abstract
In January 2021, the monitoring of circulating variants of SARS-CoV-2 was initiated in Germany under the Corona Surveillance Act, which was discontinued after July 2023. This initiative aimed to enhance pandemic containment, as specific amino acid changes, particularly in the spike protein, were associated with increased transmission and reduced vaccine efficacy. Our group conducted whole genome sequencing using the ARTIC protocol (currently V4) on Illumina's NextSeq 500 platform (and, starting in May 2023, on the MiSeq DX platform) for SARS-CoV-2 positive specimen from patients at Heidelberg University Hospital, associated hospitals, and the public health office in the Rhine-Neckar/Heidelberg region. In total, we sequenced 26,795 SARS-CoV-2-positive samples between January 2021 and July 2023. Valid sequences, meeting the requirements for upload to the German electronic sequencing data hub (DESH) operated by the Robert Koch Institute (RKI), were determined for 24,852 samples, and the lineage/clade could be identified for 25,912 samples. The year 2021 witnessed significant dynamics in the circulating variants in the Rhine-Neckar/Heidelberg region, including A.27.RN, followed by the emergence of B.1.1.7 (Alpha), subsequently displaced by B.1.617.2 (Delta), and the initial occurrences of B.1.1.529 (Omicron). By January 2022, B.1.1.529 had superseded B.1.617.2, dominating with over 90%. The years 2022 and 2023 were then characterized by the dominance of B.1.1.529 and its sublineages, particularly BA.5 and BA.2, and more recently, the emergence of recombinant variants like XBB.1.5. Since the global dominance of B.1.617.2, the identified variant distribution in our local study, apart from a time delay in the spread of new variants, can be considered largely representative of the global distribution. om a time delay in the spread of new variants, can be considered largely representative of the global distribution., Competing Interests: Declaration of competing interest None declared., (Copyright © 2023. Published by Elsevier B.V.)
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- 2024
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38. Compartments in medulloblastoma with extensive nodularity are connected through differentiation along the granular precursor lineage.
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Ghasemi DR, Okonechnikov K, Rademacher A, Tirier S, Maass KK, Schumacher H, Joshi P, Gold MP, Sundheimer J, Statz B, Rifaioglu AS, Bauer K, Schumacher S, Bortolomeazzi M, Giangaspero F, Ernst KJ, Clifford SC, Saez-Rodriguez J, Jones DTW, Kawauchi D, Fraenkel E, Mallm JP, Rippe K, Korshunov A, Pfister SM, and Pajtler KW
- Subjects
- Humans, Cell Differentiation, Disease Progression, Histological Techniques, Medulloblastoma genetics, Cerebellar Neoplasms genetics
- Abstract
Medulloblastomas with extensive nodularity are cerebellar tumors characterized by two distinct compartments and variable disease progression. The mechanisms governing the balance between proliferation and differentiation in MBEN remain poorly understood. Here, we employ a multi-modal single cell transcriptome analysis to dissect this process. In the internodular compartment, we identify proliferating cerebellar granular neuronal precursor-like malignant cells, along with stromal, vascular, and immune cells. In contrast, the nodular compartment comprises postmitotic, neuronally differentiated malignant cells. Both compartments are connected through an intermediate cell stage resembling actively migrating CGNPs. Notably, we also discover astrocytic-like malignant cells, found in proximity to migrating and differentiated cells at the transition zone between the two compartments. Our study sheds light on the spatial tissue organization and its link to the developmental trajectory, resulting in a more benign tumor phenotype. This integrative approach holds promise to explore intercompartmental interactions in other cancers with varying histology., (© 2024. The Author(s).)
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- 2024
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39. Hepatitis D infection induces IFN-β-mediated NK cell activation and TRAIL-dependent cytotoxicity.
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Groth C, Maric J, Garcés Lázaro I, Hofman T, Zhang Z, Ni Y, Keller F, Seufert I, Hofmann M, Neumann-Haefelin C, Sticht C, Rippe K, Urban S, and Cerwenka A
- Subjects
- Humans, Ligands, Interferons metabolism, Hepatitis Delta Virus genetics, Killer Cells, Natural, Tumor Necrosis Factors metabolism, Apoptosis, Carcinoma, Hepatocellular metabolism, Hepatitis D metabolism, Liver Neoplasms metabolism
- Abstract
Background and Aims: The co-infection of hepatitis B (HBV) patients with the hepatitis D virus (HDV) causes the most severe form of viral hepatitis and thus drastically worsens the course of the disease. Therapy options for HBV/HDV patients are still limited. Here, we investigated the potential of natural killer (NK) cells that are crucial drivers of the innate immune response against viruses to target HDV-infected hepatocytes., Methods: We established in vitro co-culture models using HDV-infected hepatoma cell lines and human peripheral blood NK cells. We determined NK cell activation by flow cytometry, transcriptome analysis, bead-based cytokine immunoassays, and NK cell-mediated effects on T cells by flow cytometry. We validated the mechanisms using CRISPR/Cas9-mediated gene deletions. Moreover, we assessed the frequencies and phenotype of NK cells in peripheral blood of HBV and HDV superinfected patients., Results: Upon co-culture with HDV-infected hepatic cell lines, NK cells upregulated activation markers, interferon-stimulated genes (ISGs) including the death receptor ligand tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), produced interferon (IFN)-γ and eliminated HDV-infected cells via the TRAIL-TRAIL-R2 axis. We identified IFN-β released by HDV-infected cells as an important enhancer of NK cell activity. In line with our in vitro data, we observed activation of peripheral blood NK cells from HBV/HDV co-infected, but not HBV mono-infected patients., Conclusion: Our data demonstrate NK cell activation in HDV infection and their potential to eliminate HDV-infected hepatoma cells via the TRAIL/TRAIL-R2 axis which implies a high relevance of NK cells for the design of novel anti-viral therapies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Groth, Maric, Garcés Lázaro, Hofman, Zhang, Ni, Keller, Seufert, Hofmann, Neumann-Haefelin, Sticht, Rippe, Urban and Cerwenka.)
- Published
- 2023
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40. Approaches to characterize chromatin subcompartment organization in the cell nucleus.
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Weinmann R, Frank L, and Rippe K
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- Chromosomes, Cell Nucleus metabolism, Chromatin metabolism
- Abstract
The mechanism of self-organization of chromatin subcompartments on the 0.1-1 μm scale and their impact on genome-associated activities has long been a key aspect of research on nuclear organization. Understanding the underlying structure-function relationship, however, remains challenging due to the complex hierarchical structure of chromatin and the polymorphic organization of subcompartments that assemble around it. Towards this goal, approaches to measure local properties and compositional dynamics of chromatin in its endogenous cellular environment are instrumental. Here, we discuss recent advancements in studying these features and their functional implications in protein and RNA enrichment and genome accessibility., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)
- Published
- 2023
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41. Progenitor-like cell type of an MLL-EDC4 fusion in acute myeloid leukemia.
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Schuster LC, Syed AP, Tirier SM, Steiger S, Seufert I, Becker H, Duque-Afonso J, Ma T, Ogawa S, Mallm JP, Lübbert M, and Rippe K
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- Humans, Proteins, Leukemia, Myeloid, Acute genetics
- Published
- 2023
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42. Resolving therapy resistance mechanisms in multiple myeloma by multiomics subclone analysis.
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Poos AM, Prokoph N, Przybilla MJ, Mallm JP, Steiger S, Seufert I, John L, Tirier SM, Bauer K, Baumann A, Rohleder J, Munawar U, Rasche L, Kortüm KM, Giesen N, Reichert P, Huhn S, Müller-Tidow C, Goldschmidt H, Stegle O, Raab MS, Rippe K, and Weinhold N
- Subjects
- Humans, Multiomics, Mutation, Transcriptome, Tumor Microenvironment genetics, Multiple Myeloma drug therapy, Multiple Myeloma genetics
- Abstract
Intratumor heterogeneity as a clinical challenge becomes most evident after several treatment lines, when multidrug-resistant subclones accumulate. To address this challenge, the characterization of resistance mechanisms at the subclonal level is key to identify common vulnerabilities. In this study, we integrate whole-genome sequencing, single-cell (sc) transcriptomics (scRNA sequencing), and chromatin accessibility (scATAC sequencing) together with mitochondrial DNA mutations to define subclonal architecture and evolution for longitudinal samples from 15 patients with relapsed or refractory multiple myeloma. We assess transcriptomic and epigenomic changes to resolve the multifactorial nature of therapy resistance and relate it to the parallel occurrence of different mechanisms: (1) preexisting epigenetic profiles of subclones associated with survival advantages, (2) converging phenotypic adaptation of genetically distinct subclones, and (3) subclone-specific interactions of myeloma and bone marrow microenvironment cells. Our study showcases how an integrative multiomics analysis can be applied to track and characterize distinct multidrug-resistant subclones over time for the identification of molecular targets against them., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
- Published
- 2023
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43. Nucleosome repositioning in chronic lymphocytic leukemia.
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Piroeva KV, McDonald C, Xanthopoulos C, Fox C, Clarkson CT, Mallm JP, Vainshtein Y, Ruje L, Klett LC, Stilgenbauer S, Mertens D, Kostareli E, Rippe K, and Teif VB
- Subjects
- Humans, Chromatin, Transcription Factors metabolism, Disease Progression, Nucleosomes genetics, Leukemia, Lymphocytic, Chronic, B-Cell genetics
- Abstract
The location of nucleosomes in the human genome determines the primary chromatin structure and regulates access to regulatory regions. However, genome-wide information on deregulated nucleosome occupancy and its implications in primary cancer cells is scarce. Here, we conducted a genome-wide comparison of high-resolution nucleosome maps in peripheral blood B cells from patients with chronic lymphocytic leukemia (CLL) and healthy individuals at single-base-pair resolution. Our investigation uncovered significant changes of nucleosome positioning in CLL. Globally, the spacing between nucleosomes-the nucleosome repeat length (NRL)-is shortened in CLL. This effect is stronger in the more aggressive IGHV-unmutated CLL subtype than in the IGHV-mutated CLL subtype. Changes in nucleosome occupancy at specific sites are linked to active chromatin remodeling and reduced DNA methylation. Nucleosomes lost or gained in CLL marks differential binding of 3D chromatin organizers such as CTCF as well as immune response-related transcription factors and delineated mechanisms of epigenetic deregulation. The principal component analysis of nucleosome occupancy in cancer-specific regions allowed the classification of samples between cancer subtypes and normal controls. Furthermore, patients could be better assigned to CLL subtypes according to differential nucleosome occupancy than based on DNA methylation or gene expression. Thus, nucleosome positioning constitutes a novel readout to dissect molecular mechanisms of disease progression and to stratify patients. Furthermore, we anticipate that the global nucleosome repositioning detected in our study, such as changes in the NRL, can be exploited for liquid biopsy applications based on cell-free DNA to stratify patients and monitor disease progression., (© 2023 Piroeva et al.; Published by Cold Spring Harbor Laboratory Press.)
- Published
- 2023
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44. Resolving the spatial architecture of myeloma and its microenvironment at the single-cell level.
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John L, Poos AM, Brobeil A, Schinke C, Huhn S, Prokoph N, Lutz R, Wagner B, Zangari M, Tirier SM, Mallm JP, Schumacher S, Vonficht D, Solé-Boldo L, Quick S, Steiger S, Przybilla MJ, Bauer K, Baumann A, Hemmer S, Rehnitz C, Lückerath C, Sachpekidis C, Mechtersheimer G, Haberkorn U, Dimitrakopoulou-Strauss A, Reichert P, Barlogie B, Müller-Tidow C, Goldschmidt H, Hillengass J, Rasche L, Haas SF, van Rhee F, Rippe K, Raab MS, Sauer S, and Weinhold N
- Subjects
- Humans, Cell Communication, Chromatin Immunoprecipitation Sequencing, Clone Cells, Disease Progression, Tumor Microenvironment genetics, Multiple Myeloma genetics
- Abstract
In multiple myeloma spatial differences in the subclonal architecture, molecular signatures and composition of the microenvironment remain poorly characterized. To address this shortcoming, we perform multi-region sequencing on paired random bone marrow and focal lesion samples from 17 newly diagnosed patients. Using single-cell RNA- and ATAC-seq we find a median of 6 tumor subclones per patient and unique subclones in focal lesions. Genetically identical subclones display different levels of spatial transcriptional plasticity, including nearly identical profiles and pronounced heterogeneity at different sites, which can include differential expression of immunotherapy targets, such as CD20 and CD38. Macrophages are significantly depleted in the microenvironment of focal lesions. We observe proportional changes in the T-cell repertoire but no site-specific expansion of T-cell clones in intramedullary lesions. In conclusion, our results demonstrate the relevance of considering spatial heterogeneity in multiple myeloma with potential implications for models of cell-cell interactions and disease progression., (© 2023. Springer Nature Limited.)
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- 2023
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45. Intestinal B cells license metabolic T-cell activation in NASH microbiota/antigen-independently and contribute to fibrosis by IgA-FcR signalling.
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Kotsiliti E, Leone V, Schuehle S, Govaere O, Li H, Wolf MJ, Horvatic H, Bierwirth S, Hundertmark J, Inverso D, Zizmare L, Sarusi-Portuguez A, Gupta R, O'Connor T, Giannou AD, Shiri AM, Schlesinger Y, Beccaria MG, Rennert C, Pfister D, Öllinger R, Gadjalova I, Ramadori P, Rahbari M, Rahbari N, Healy ME, Fernández-Vaquero M, Yahoo N, Janzen J, Singh I, Fan C, Liu X, Rau M, Feuchtenberger M, Schwaneck E, Wallace SJ, Cockell S, Wilson-Kanamori J, Ramachandran P, Kho C, Kendall TJ, Leblond AL, Keppler SJ, Bielecki P, Steiger K, Hofmann M, Rippe K, Zitzelsberger H, Weber A, Malek N, Luedde T, Vucur M, Augustin HG, Flavell R, Parnas O, Rad R, Pabst O, Henderson NC, Huber S, Macpherson A, Knolle P, Claassen M, Geier A, Trautwein C, Unger K, Elinav E, Waisman A, Abdullah Z, Haller D, Tacke F, Anstee QM, and Heikenwalder M
- Subjects
- Humans, Mice, Animals, Mice, Inbred C57BL, Liver pathology, Fibrosis, Liver Cirrhosis complications, Mice, Transgenic, Immunoglobulin A metabolism, Immunoglobulin A pharmacology, Disease Models, Animal, Diet, High-Fat adverse effects, Non-alcoholic Fatty Liver Disease complications, Carcinoma, Hepatocellular pathology, Liver Neoplasms genetics, Microbiota
- Abstract
Background & Aims: The progression of non-alcoholic steatohepatitis (NASH) to fibrosis and hepatocellular carcinoma (HCC) is aggravated by auto-aggressive T cells. The gut-liver axis contributes to NASH, but the mechanisms involved and the consequences for NASH-induced fibrosis and liver cancer remain unknown. We investigated the role of gastrointestinal B cells in the development of NASH, fibrosis and NASH-induced HCC., Methods: C57BL/6J wild-type (WT), B cell-deficient and different immunoglobulin-deficient or transgenic mice were fed distinct NASH-inducing diets or standard chow for 6 or 12 months, whereafter NASH, fibrosis, and NASH-induced HCC were assessed and analysed. Specific pathogen-free/germ-free WT and μMT mice (containing B cells only in the gastrointestinal tract) were fed a choline-deficient high-fat diet, and treated with an anti-CD20 antibody, whereafter NASH and fibrosis were assessed. Tissue biopsy samples from patients with simple steatosis, NASH and cirrhosis were analysed to correlate the secretion of immunoglobulins to clinicopathological features. Flow cytometry, immunohistochemistry and single-cell RNA-sequencing analysis were performed in liver and gastrointestinal tissue to characterise immune cells in mice and humans., Results: Activated intestinal B cells were increased in mouse and human NASH samples and licensed metabolic T-cell activation to induce NASH independently of antigen specificity and gut microbiota. Genetic or therapeutic depletion of systemic or gastrointestinal B cells prevented or reverted NASH and liver fibrosis. IgA secretion was necessary for fibrosis induction by activating CD11b+CCR2+F4/80+CD11c-FCGR1+ hepatic myeloid cells through an IgA-FcR signalling axis. Similarly, patients with NASH had increased numbers of activated intestinal B cells; additionally, we observed a positive correlation between IgA levels and activated FcRg+ hepatic myeloid cells, as well the extent of liver fibrosis., Conclusions: Intestinal B cells and the IgA-FcR signalling axis represent potential therapeutic targets for the treatment of NASH., Impact and Implications: There is currently no effective treatment for non-alcoholic steatohepatitis (NASH), which is associated with a substantial healthcare burden and is a growing risk factor for hepatocellular carcinoma (HCC). We have previously shown that NASH is an auto-aggressive condition aggravated, amongst others, by T cells. Therefore, we hypothesized that B cells might have a role in disease induction and progression. Our present work highlights that B cells have a dual role in NASH pathogenesis, being implicated in the activation of auto-aggressive T cells and the development of fibrosis via activation of monocyte-derived macrophages by secreted immunoglobulins (e.g., IgA). Furthermore, we show that the absence of B cells prevented HCC development. B cell-intrinsic signalling pathways, secreted immunoglobulins, and interactions of B cells with other immune cells are potential targets for combinatorial NASH therapies against inflammation and fibrosis., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)
- Published
- 2023
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46. Approaches for single-cell RNA sequencing across tissues and cell types.
- Author
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Sant P, Rippe K, and Mallm JP
- Subjects
- Sequence Analysis, RNA methods, Single-Cell Analysis methods, RNA genetics, Gene Expression Profiling methods, High-Throughput Nucleotide Sequencing methods
- Abstract
Single-cell sequencing of RNA (scRNA-seq) has advanced our understanding of cellular heterogeneity and signaling in developmental biology and disease. A large number of complementary assays have been developed to profile transcriptomes of individual cells, also in combination with other readouts, such as chromatin accessibility or antibody-based analysis of protein surface markers. As scRNA-seq technologies are advancing fast, it is challenging to establish robust workflows and up-to-date protocols that are best suited to address the large range of research questions. Here, we review scRNA-seq techniques from mRNA end-counting to total RNA in relation to their specific features and outline the necessary sample preparation steps and quality control measures. Based on our experience in dealing with the continuously growing portfolio from the perspective of a central single-cell facility, we aim to provide guidance on how workflows can be best automatized and share our experience in coping with the continuous expansion of scRNA-seq techniques.
- Published
- 2023
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47. The pre-existing T cell landscape determines the response to bispecific T cell engagers in multiple myeloma patients.
- Author
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Friedrich MJ, Neri P, Kehl N, Michel J, Steiger S, Kilian M, Leblay N, Maity R, Sankowski R, Lee H, Barakat E, Ahn S, Weinhold N, Rippe K, Bunse L, Platten M, Goldschmidt H, Müller-Tidow C, Raab MS, and Bahlis NJ
- Subjects
- Humans, CD8-Positive T-Lymphocytes, Immunotherapy, Clone Cells pathology, Multiple Myeloma drug therapy, Antibodies, Bispecific therapeutic use
- Abstract
Bispecific T cell engagers (TCEs) have shown promise in the treatment of various cancers, but the immunological mechanism and molecular determinants of primary and acquired resistance to TCEs remain poorly understood. Here, we identify conserved behaviors of bone marrow-residing T cells in multiple myeloma patients undergoing BCMAxCD3 TCE therapy. We show that the immune repertoire reacts to TCE therapy with cell state-dependent clonal expansion and find evidence supporting the coupling of tumor recognition via major histocompatibility complex class I (MHC class I), exhaustion, and clinical response. We find the abundance of exhausted-like CD8
+ T cell clones to be associated with clinical response failure, and we describe loss of target epitope and MHC class I as tumor-intrinsic adaptations to TCEs. These findings advance our understanding of the in vivo mechanism of TCE treatment in humans and provide the rationale for predictive immune-monitoring and conditioning of the immune repertoire to guide future immunotherapy in hematological malignancies., Competing Interests: Declaration of interests The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. P.N. reports receiving speaker’s bureau honoraria from BMS, Janssen, and Sanofi, and is a consultant/advisory board member for BMS and Janssen. C.M.-T. received research funding from Pfizer and BiolineRX. M.-S.R. reports receiving speaker’s bureau honoraria from Amgen, BMS, Sanofi, and Janssen, and is a consultant/advisory board member for BMS, GSK, Amgen, Janssen, and Pfizer. He received research funding from Amgen, Sanofi, and Janssen. N.J.B. reports receiving speaker’s bureau honoraria from Amgen, BMS, Sanofi, Pfizer, and Janssen, and is a consultant/advisory board member for BMS, Janssen, and Pfizer. All other authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2023
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48. Epigenetic signals that direct cell type-specific interferon beta response in mouse cells.
- Author
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Muckenhuber M, Seufert I, Müller-Ott K, Mallm JP, Klett LC, Knotz C, Hechler J, Kepper N, Erdel F, and Rippe K
- Subjects
- Animals, Humans, Mice, Chromatin genetics, Antiviral Agents pharmacology, Epigenesis, Genetic genetics, Interferon-beta genetics, Histones metabolism
- Abstract
The antiviral response induced by type I interferon (IFN) via the JAK-STAT signaling cascade activates hundreds of IFN-stimulated genes (ISGs) across human and mouse tissues but varies between cell types. However, the links between the underlying epigenetic features and the ISG profile are not well understood. We mapped ISGs, binding sites of the STAT1 and STAT2 transcription factors, chromatin accessibility, and histone H3 lysine modification by acetylation (ac) and mono-/tri-methylation (me1, me3) in mouse embryonic stem cells and fibroblasts before and after IFNβ treatment. A large fraction of ISGs and STAT-binding sites was cell type specific with promoter binding of a STAT1/2 complex being a key driver of ISGs. Furthermore, STAT1/2 binding to putative enhancers induced ISGs as inferred from a chromatin co-accessibility analysis. STAT1/2 binding was dependent on the chromatin context and positively correlated with preexisting H3K4me1 and H3K27ac marks in an open chromatin state, whereas the presence of H3K27me3 had an inhibitory effect. Thus, chromatin features present before stimulation represent an additional regulatory layer for the cell type-specific antiviral response., (© 2023 Muckenhuber et al.)
- Published
- 2023
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49. Assessing the Phase Separation Propensity of Proteins in Living Cells Through Optodroplet Formation.
- Author
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Rademacher A, Erdel F, Weinmann R, and Rippe K
- Subjects
- Light, Microscopy, Fluorescence, Organelles metabolism, Protein Domains, Proteins metabolism, Deoxyribodipyrimidine Photo-Lyase metabolism
- Abstract
Phase separation is emerging as a key mechanism to describe the formation of membraneless organelles in the cell. It depends on the multivalent (self-) interaction properties of the macromolecules involved and can be observed in aqueous solutions under controlled conditions in vitro with purified components. However, to experimentally demonstrate that this process indeed occurs in the complex environment of living cells remains difficult. Here, we describe an assay based on light-induced association of proteins into complexes termed optodroplets that are in the hundred nm to μm size range. The formation and dissociation of these optodroplets can be followed over time in living cells by fluorescence microscopy to evaluate the propensity of proteins to demix and to form phase-separated subcompartments. The optodroplet assay is based on the fusion of a protein of interest with the photolyase homology region (PHR) protein domain from Arabidopsis thaliana, which can undergo reversible homo-oligomerization upon illumination with blue light. Using this approach, candidate proteins and their interaction-deficient or interaction-enhanced variants can be compared to each other or to reference proteins with known phase separation features. By quantifying the resulting microscopy images, the propensity of a given protein construct to assemble into a phase-separated subcompartment can be assessed., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)
- Published
- 2023
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50. Author Correction: Genomic footprints of activated telomere maintenance mechanisms in cancer.
- Author
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Sieverling L, Hong C, Koser SD, Ginsbach P, Kleinheinz K, Hutter B, Braun DM, Cortés-Ciriano I, Xi R, Kabbe R, Park PJ, Eils R, Schlesner M, Brors B, Rippe K, Jones DTW, and Feuerbach L
- Published
- 2022
- Full Text
- View/download PDF
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