DNA CRISPR

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昱枢智
7 years ago
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2 DNA CRISPR

3 ETC 93

4 BIG BIG zhouml@big.ac.cn Tomas Lindahl

5 DNA K-mer PacBio DNA Tomas Lindahl Tomas Lindahl

7 聚焦

9 聚焦

10 11 5

11 聚焦

12 BIG - BIG - BIG - BIG

13 聚焦

15 聚焦

16 10 28 BIG Olson Maynard Olson Olson 2 Olson Olson 1988 BIG YAC Olson Olson 2011 Olson

17 聚焦 5 science nature BIG BIG

19 聚焦

21 聚焦 CasTech CasTech CasPoint CasPoint, 10 30

22 ,

23 聚焦 Lindahl Genomics Proteomics & Bioinformatics GPB Tomas Lindahl Aziz Sancar Paul Modrich 2015 Lindahl 2009 GPB DNA 2015 Lindahl GPB Lindahl DNA Lindahl 2013 Lindahl GPB DNA My Journey to DNA Repair

24 Web of Science SCI Genomics,Proteomics&Bioinformatics GPB 2015 SSCI GPB Web of Science GPB CI 5% GPB CI

25 学术

26 ( )

27 学术 PSA DNA PSA PSA 4-10ng/ml 25%-40% PSA Identification of specific DNA methylation sites on the Y-chromosome as biomarker in prostate cancer Oncotarget marker 66 Y 973 Y 6 DNA ROC 94.6% 78.3% PSA DNA ROC

28 Li and Durbin(2011) PSMC 2 Kingman 300 Kingman - robustness Molecular Biology and Evolution 1 TNSFS A Gazave, B TNSFS

29 学术 Differential Responses to Lithium in Hyperexcitable Neurons from Bipolar Patients induced pluripotent stem cell, ipsc BD hippocampal dentate gyrus granule cell-like neurons LR NR Bipolar disease, BD Hyperexcitability WHO BD BD ipsc BD BD BD - BD BD

30 UCL K-mer K-mer KGCAK K-mer Biology Direct motif Ensembl Phytozome NCBI K-mer K-mer 8000 DNA cdna CDS ncrna K 2 10 K 1 5 K-mer K-mer K-mer K-mer K-mer

31 学术 Web API IC4R(Information Commons for Rice) Nucleic Acids Research IC4R 5000 RNA-Seq Wiki Community Curation IC4R RAP-DB MSU-RGAP 863

32 ICGC SNV TCGA 2013 CasBreak CasTech EMBL ICGC-TCGA Dream Somatic Mutation 98.3% F1 Challenge SMC SMC SV F1 98.5% WGS ICGC MD Anderson SMC CasTech HKU-BGI BAL CasPoint CasTech SNV SV 99.8% F1 Bina Roche Rutgers - BROAD

33 学术 PacBio PacBio SMRT cdna Cell 1Gb reads PacBio read 14kb N50 19kb cdna PacBio LncRNA de novo PacBio read de novo 5Mb DNA SMRT Cell finish 5 IPD ratio,, Contig N50 100kb de IPD ratio novo 50 PacBio m6a, PacBio 5mC 5hmC 4mC 30 PacBio scaffold 10 PacBio 2..PacBio read subread cdna PacBio DNA PacBio BAC GC DNA

34 Tomas Lindahl 2015 Tomas Lindahl DNA DNA DNA DNA DNA DNA DNA / DNA i - DNA -DNA 3- DNA DNA ii - nobelprize.org DNA AP Walter Verly iii EB O6- - DNA MGMT Ada EB DNA DNA DNA iv DNA AlkB Barbara Sedgwick DNA ErlingSeeberg DNA FTO ALKBH5 3- RNA m6a

35 学术 DNA DNase III DNase IV TREX1 FEN1 FEN1 5-3 DNA TREX1 DNA 3-5 TREX1 SLE Aicardi-Goutières syndrome Yanick Crow 2007 DNA DNA TREX1 Tomas Lindahl. Genomics, Proteomics & Bioinformatics, Volume 11, Issue 1, February Deborah Barnes 2013, Pages 2 7 DNA DNA Ada DNA DNA Ada 1986 ATP XPA ICRF DNA Clare Hall ATP NAD Cancer Research UK DNA DNA DNA I DNA III DNA IV Lee Johnston DNA I Genomics, Proteomics & Bioinformatics 2013 DNA I

36 DNA DNA DNA

37 科普 CRISPR/Cas9 MSTN DNA CRISPR/Cas CRISPR/Cas9 CRISPR Clustered Regularly Interspersed Short Palindromic Repeats 1. CRISPR/Cas9 DNA 2015 A CRISPR/Cas CRISPR CRISPR/Cas9 PAM Protospacer adjacent motifs- CRISPR/Cas9 ZFN DNA TALEN DNA PAM PAM CRISPR

38 2 CRISPR CRISPR Cas CRISPR CRISPR RNA Cas PAM DNA DNA DNA CRISPR/Cas9 RNA Cas9 2CRISPR/Cas9 CRISPR/Cas9 DNA RNA PAM DNA 3 RNA guide RNA, grna Cas9 RNA( RNA RNA1 RNA2) Cas9 PAM RNA NGG N PAM

39 科普 ips CRISPR/Cas9 ips CRISPR HIV Nature CRISPR/Cas9 3CRISPR/Cas9 Cas9 DNA CRISPR/Cas9 DNA DNA DNA CRISPR/Cas9 CRISPR CRISPR/Cas9 CRISPR/Cas9 CRISPR/Cas9 RNA DNA [1]Doudna, J.A.; Charpentier, E., CRISPR/ Genome editing. The new frontier of genome Cas9 engineering with CRISPR-Cas9. Science, Cas9 2014, 346, (6213), [ ] CRISPR/Cas9 [2] Fang, R.; Chang, F.; Sun, Z.-L.; Li, N.; Meng, Q.-Y., New Method of Genome Editing Derived From CRISPR/Cas9. CRISPR/Cas9 ActaAgronomicaSinica, 2013, 40, (8), 691. ips

40 RNA U DNA RNA RNA RNA DNA U U you DNA RNA mrna DNA 5- m5c 5- hm5c mrna RNA DNA mrna 5-7- GTP DNA mrna5 - RNA T DNA U RNA A G C DNA RNA DNA A T,G C A U G C

41 文化 Tomas DNA Lindahl Paul Clare Hall Modrich Aziz Laboratories Sancar DNA DNA 2000 WHO DNA DNA DNA DNA DNA DNA DNA DNA DNA

42 DNA. (Tim Hunt)(2001 ) DNA

43 文化 Genomics Proteomics & Bioinformatics (GPB) My Journey to DNA Repair GPB ( pii/s ) 2014 DNA Beverly 6 (Arne Klungland) Tomas Lindahl Conference on DNA repair DNA DNA DNA RNA RNA m6a 6- RNA RNA , (I still enjoy very much doing science. It is pleasure, it is very interesting and it is stimulating. It changes all the time. I would like to be here around hundred years to see how science develops.-my Journey to DNA Repair) 2009

44 研究员专访编者按杨运桂博士是中国科学院百人计划获得者, 现任中科院北京基因组研究所研究员 1995 年毕业于复旦大学生命科学学院,2000 年获得中科院上海药物所理学博士学位 ; 后又分别在世界卫生组织国际癌症研究署 ( 法国里昂 ) 和英国癌症研究署从事博士后研究, 目前主要研究领域是 RNA 甲基化表观转录组特征调控和功能研究在学生眼里, 杨运桂研究员平易近人, 直率认真而又不失风趣幽默, 对学生既严格又关心他办公室的墙上挂满了已毕业学生的照片, 而办公桌上的一角摆放着家人的照片在与他长谈中, 笔者不仅能感受到他对科学探索的执着与坚定, 也能感受到他对对生活的积极与乐观 PI 100

45 文化. (Tomas Lindahl) DNA RNA DNA 1974 PNAS 1992 Nature DNA RNA RNA DNA RNA RNA RNA The Age of Wonder 6 9

46 Paper

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50 ready to submit under review in press 3. Manuscript received by editorial office 1. Ready to submit 4. With editor Awaiting editor assignment Editor assignment Technical check in progress 2. Submitted to journal Editor declined invitation

51 文化 50% Decision letter being prepared 9. Revision submitted to journal Review(s) invited 10. Accepted 5. Under review 11. Transfer copyright form decline 12. Uncorrected proof 6. Required reviews completed 13. In press, corrected proof 14. Manuscript sent to production 7. Evaluating recommendation 15. in production decision 8. Minor revision/ Major revision Minor revision Major revision

53 文化 :!?!

54 Tara-cry cry

2015 Intellectual Sensitive 30 Physical A T G C DNA

2015 Intellectual Sensitive 30 Physical A T G C DNA DNA 7 24 Zemin Ning Kai Ye BIG BIG 1 104 100101 010-84097548 www.big.ac.cn zhouml@big.ac.cn REV1 FANCD2 DNA 6 18 50 聚焦 70 88 7 22 20 7 3 complex indels