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(12) Patent Application Publication (10) Pub. No.: US 2011/0091454 A1 Diber Et Al

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US 2011 0091454A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2011/0091454 A1 Diber et al. (43) Pub. Date: Apr. 21, 2011 (54) METHODS AND SYSTEMS FOR Beck, Kfar Saba (IL); Wei-Yong ANNOTATING BOMOLECULAR Zhu, Plainsboro, NJ (US); Alon SEQUENCES Wasserman, New York, NY (US); Chen Chermesh, Mishmar (76) Inventors: Alex Diber, Rishon-LeZion (IL); HaShiva (IL); Idit Azar, Tel-Aviv Sarah Pollock, Tel-Aviv (IL); Zurit (IL); Rotem Sorek, Rechovot (IL); Levine, Herzlia (IL); Sergey Jeanne Bernstein, Kfar Yona (IL) Nemzer, RaAnana (IL); Vladimir Grebinskiy, Highland Park, NJ (21) Appl. No.: 12/701,651 (US); Brian Meloon, Plainsboro, NJ (US); Andrew Olson, (22) Filed: Feb. 8, 2010 Northport, NY (US): Avi Related U.S. Application Data Rosenberg, Kfar Saba (IL); Ami Haviv, Hod-HaSharon (IL); Shaul (63) Continuation of application No. 11/043,860, filed on Zevin, Mevaseret Zion (IL); Tomer Jan. 27, 2005. Zekharia, Givataim (IL); Zipi (60) Provisional application No. 60/539,129, filed on Jan. Shaked, Tel-Aviv (IL); Moshe 27, 2004. Olshansky, Haifa (IL); Ariel Farkash, Haifa (IL); Eyal Publication Classification Privman, Tel-Aviv (IL); Amit (51) Int. Cl. Novik, Beit-YeHoshua (IL); Naomi A 6LX 39/395 (2006.01) Keren, Givat Shmuel (IL); Gad S. C07K 6/00 (2006.01) Cojocaru, Ramat-HaSharon (IL); GOIN 33/53 (2006.01) Pinch as Akiva, Ramat-Gan (IL); Yossi Cohen, Woking (GB); Ronen A6IP35/00 (2006.01) Shemesh, Modiin (IL); Osnat (52) U.S. Cl. ................ 424/133.1: 530/387.9; 424/139.1; Sella-Tavor, Kfar-Kish (IL); Liat 530/387.3; 436/501 Mintz, East Brunswick, NJ (US); (57) ABSTRACT Hanging Xie, Lambertville, NJ (US); Dvir Dahary, Tel-Aviv (IL); Polypeptide sequences and polynucleotide sequences are Erez. Levanon, Petach-Tikva (IL); provided. Also provided are annotative information concern Shiri Freilich, Haifa (IL); Nili ing Such sequences and uses for these sequences. O Externa ser 4. Database interface Processing it. Application VOdie Database Patent Application Publication Apr. 21, 2011 Sheet 1 of 37 US 2011/0091454 A1 4. n Processing it. Application / 18 Module 4. / Processing init 8 Patent Application Publication Apr. 21, 2011 Sheet 2 of 37 US 2011/0091454 A1 ~NN A | ~N ~__)~~ Z‘61– \|/ N |× \/ Patent Application Publication Apr. 21, 2011 Sheet 3 of 37 US 2011/0091454 A1 of 1.1 epithelial ceili tumors ... Carciorra ... alien O'CarClona ... 1.2 obiliar Carcinona 1.2 Fiese cfia ceili tutors 2. SarCOf a .2.1.1 iposarcoma 1.2.1.2 rhabdomyosarconna 1.2.1.3 pnet 1.2.1.4 ewing sarcoma 1.3 food it fors 1.3.3 lymphoma .3.2 leukemia 1.3.3 myeloma 1.4 endocrine fiors 1.4.1 pheocromocytoma 4.2 Carci Cic 2 endocrine syster 2. a dreaf 2.1.1 pheocroinocytona 2.2 pancreas 2.2.1 islets of langerhans 2.3 regroeidocrine 2.3.1 hypothalamus 23.2 Ca"Croid 2.4 thyroid 3 Wascar tissue 3. f arteries 3. ... acia 3.2 Veii. Fig. 4. Patent Application Publication Apr. 21, 2011 Sheet 4 of 37 US 2011/0091454 A1 4 genitorinary syster 4. urinary systern 4.1 biadier 4.1.2 kidney 4.2 genital systern 4.2.1 women genital system 4.2.1 Cervix 4.2.1.2. Oway 4.2.1.3 liters 4.2.1.3.1 erado retriuirr 4.2.2 men gentile system 4.2.2.1 prostate 4.2.2.2 testis 4.2.2.2.1 epididymis 5 scies 5.1 rhabdomyosarconna 5.2 tongue 5.3 after .4 fearf 5. Liters Occi 6.1 peripheral blood 6.1.1 erythroid ine 6, i.2 leukocyte 6.1.2.1 lymphoid system 6.1.2.1. 1 lymphoma 6.1.2.1.2 spleen 6.1.2.1.3 thaiaritis 6.2 step ces 6.2.1 myeloid 6.2.2 yeoma 6.3 Borge arrow Fig. 4 (Cont.) 6.4 feifreria Patent Application Publication Apr. 21, 2011 Sheet 5 of 37 US 2011/0091454 A1 7 nerve system 7.1 CNS, central nervous system 7 brai 7... Ceer 7.1.2 Cerebe in 7.1.1.3 pitituary gland 7.14 hypothalamus 7.1.1.5 ha anus 7.1.16 olfactory 7.1.1.7 hippocampus 7.1.1.8 amygdala 7. 9 for a de 7.1.1.10 pnet 7.2 Embryonal nerve system 7.2.1 primitive neuroectodern 7.3 retiria 7.3.1 retiricasionna 8 reast 8. du cital breas: 8.1.1. dicta Carcircra 8.2 ou lar carcia Opra 8.3 mammary skeeter 9. One 9. i. ewing sarcoma 9.1.2 craniofacia 9, .2. Cavariri 9.2 corrective tiss Lie 9.2.1 trabeculae 9.2.2 cartilage Fig. 4 (Cont.) Patent Application Publication Apr. 21, 2011 Sheet 6 of 37 US 2011/0091454 A1 embryo O. arrior .2 cric 10.3 primitive neuroectodern 10.4 piacenta exocrine system 11.1 pancreas 11.1.1 islets of langerhans 11.2 prostate 11.3 saivary gland 12 face organs 2. rose 12.2 ear 2.2. COcea 12.3 eye 2.3. retira 2.3. retiricastoria 2.3.2 ens 12.4 riotti 12.5 tongue 3 gastrointestina syster 13. 1 frucOSa 13.2 Stoira Ci 13.3 iriesiiie 3.3. COO recta 3.3. CCC 3.4 hepatobiliary systern 3.4 live 13.4.2 biliary system 13.4.2.1 gai bladder 13.5 pancreas 13.5.1 islets of langerhans Fig. 4 (Cont.) Patent Application Publication Apr. 21, 2011 Sheet 7 of 37 US 2011/0091454 A1 4 respiratory system 14.1 nasopharynx 14.2 lung 14.2.1 sma cellung carcinoma Sk 1.1 certis 15.1. melanocyte 6 fat tissue 16.1 iposarcona Fig. 4 (Cont.) Patent Application Publication Apr. 21, 2011 Sheet 8 of 37 US 2011/0091454 A1 |09 |0+ Foz e6eueoja u Oopeiae now Patent Application Publication Apr. 21, 2011 Sheet 9 of 37 US 2011/0091454 A1 80eds Jeyneoexe Jenieoexe auleoidetie-dueli je feu ujeoideuerqueueused effieu use doejonu euejqueu jeepnu menu auOSIXOjed t 3ueiguelii et u e pu030. 8Leigueueipt Otool XLei eLu(OOL UOLuO3Ou needde fog unno.8. Oil Seidopte OSOAQ JO)883;SCAO u08 ( JoelexSOA) LSedoA) 9. l u:80i/suo go equir N Patent Application Publication Apr. 21, 2011 Sheet 12 of 37 US 2011/0091454 A1 Œ.È $DukeD?ö(5£.DukeC {}Tõ§7,5 §82- -º* $DukeB genomicDNA ºB ?ë,,DukeA adenocarcinoma pancreas breas? ?jver testis lung heart ovary thymus sp?een kidney p?acen?a stornach brain puuduI04800uðþýtrººfds ? Patent Application Publication Apr. 21, 2011 Sheet 13 of 37 US 2011/0091454 A1 (s s C S2 . -- S; C s 2 O Ewing Ost San is2 i 2 < : Saf Corra Cei-lines si CO ag C. c. is Celinetai I S 5 () a : & 8 & 8 & S. 8 & & &SS &: S SS Fig. 9 . 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To generate meaningful amounts of data, however, ANNOTATING BIOMOLECULAR high throughput template preparation, sequencing and analy SEQUENCES sis protocols must be applied. As such, the number of new genes identified as well as the statistical significance of the RELATIONSHIP TO EXISTING APPLICATIONS data is proportional to the number of clones sequenced as well as the complexity of the tissue being analyzed Adams et al. 0001. The present application claims priority as a Con (1995) Nature 377:3-173; Hillier et al. (1996) Genome Res. tinuation application from U.S. patent application Ser. No. 6:807-828. 11/043,860, filed on Jan. 27, 2005, which claims priority from 0011 Subtractive cloning Subtractive cloning offers an U.S. Provisional Patent Application No. 60/539,129 filed Jan.
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