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biosun 2012

???????? ??? ???? RNA?????? ???????????? ??????? ????? ????:coding region, noncoding RNA genes ??????? ????:?????????? BioSun????. What is computational biology. Computational biology is a new field of research which develops models and softwa

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biosun 2012

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    1. ??????? ??? ?????????????? http://www.biosun.org.cn 2012/5/20

    2. ???? ???? ??? ???? RNA?????? ???????????? ??????? ????? ????:coding region, noncoding RNA genes ??????? ????:?????????? BioSun????

    3. What is computational biology Computational biology is a new field of research which develops models and software implementations for computational problems in molecular biology, biotechnology, and genetics. Such means are needed both in the basic research and in the industrial applications of biotechnology. Computer-aided DNA sequencing, sequence comparison, prediction of protein structures, docking of molecules, and the interpretation of electron microscopy or NMR data are examples of typical computationally intensive tasks. Bioinformatics refers to the development and use of the (molecular) biological databases

    4. ??????? ?????????????,????? ???,??????,???????? ???????????,??????? ????????????????,???? ????;???????????????? ?????

    6. ??? ??,????????????, ????????NCBI???Genbank, ???????????EBI,????? ??????DDBJ?? ???Nucleic Acid Res.????? ??????????? ????????????

    7. ???? ????????????????? ?????:????????RNA???????????????????????? ??????????????? ??????:?????????????;?????????;???????? ?;??????? ?????:blast,??NCBI,EBI?? ?????:????????

    8. ?????????? ????:????????? Wx=g+rx ????????:???????? ???,??????????????????????

    9. Needleman-Wunsch??

    10. RNA??????

    11. ??????RNA?????? tRNA???????? ??????? 5’?3’??????(UTR) ???????????

    12. RNA?????????? ???(helical regions):?? ???(hairpin loop):??? ???(interior loop):??? ???(bulge loop):??? ????(multibranch loop):??? ????:???

    14. RNA????????? RNA???????=???????????? ?????????????????? ???????: ?????????,1995,19:293

    15. ??????? Salser????? Turner????? http://www.bioinfo.rpi.edu/~zukerm/rna/ ?????????+???????

    16. ????? 5`-AC-3` -1.8 5`-CG-3` -3.4 3`-UG-5` 3`-GC-5` 5`-GU-3` -1.8 H(4,10)=4.4 3`-CA-5` TotalG=-1.8-3.4-1.8+4.4=-2.6 (Kcal/Mol)

    17. RNA?????????? Dynamic programming algorithms Kinetic folding algorithms Genetic algorithms Comparative methods Higgs. Quarterly Reviews of Biophysics 33:199-253,2000

    18. Dynamic programming algorithms ?????????,?????? ?????,???????????? ?????????????,???? ????RNA??????????? Maximum matching model (Nussinov et al. 1980) Minimum free energy (Zuker, NAR 1981)

    19. Zuker’s Minimum free energy

    20. Kinetic folding algorithms ??RNA?????????????? ?????,??RNA?????????? ??????????????????? ??????????????????? ?,???????????,???RNA? ????

    21. ??????????????,?? ?????????????????? ?RNA????,??????????? ??????????

    22. Genetic algorithms ????,?????????????? ???,???????,????????? ????????,???????????? ???,???????????,????? ?????,???????,?Monte-Carlo ??????????

    23. ?RNA????????,????? ???????RNA????????,? ?,???????????????? ??

    24. Comparative methods ????:???????RNA???Phe- tRNA??,???????????,?? ??????????????????? ?,??????????,?????? ????RNA???????

    26. ????????????? Zuker????????Pipas????????? ????????????,??????,???? ??,?????????: ?Pipas???,???????????,???????????,??????,????????????????????? ?Zuker???,??????????????????,?????????????,???????

    27. ??????? ??????Zuker??(MFOLD),??? ???????,??????RNA????, ???????RNA????,??????? ??,??????????????,??? ????????????????????? ???????,??????????

    28. ?????

    29. ??? ?????H(S,E,L)???????: S:?????;E:?????; L:?????

    30. ??????? ????RNA??,???N,Hk(Sk,Ek,Lk) (k=1,2,…,n)???[i,j] (1=i<j=N)??n????,???????: i=S1<E1<S2<E2…<Sk<Ek<…<Sn<En=j ???n???????[i,j]????????

    31. ????????

    38. ???? RS?HD:?????????GU?? RS????HD ????????GU????,T3.0;????????GU?????,T25 ????????3 bp RS??????54.65% (523/957),HD ?52.14 (499/957),Zuker???32.92 (315/957) ?

    39. BJRNAFold?? ??RS?HD????,??,??? ??????????,?Zuker???? ???,???????BJRNAFold ?1139tRNA????,BJRNAFold??RS??? ???????,BJRNAFold?MFold???????

    40. ???????? ??????

    43. ??,??????:?????? ????????????pBV220,?? ???,???????,?????? ?????????????????? ???,?????????????, ????????????????,? ??????,??????????? ?????????????

    44. ???? Table 1 Related data of 22 foreign genes carried by pBV220 vector -------------------------------------- No. Name Level Class D Ref. No. Name Level Class D Ref. -------------------------------------- 1 PCG12 1.96 1 9 3 12 PCG14 23.41 2  11 3 2 PCG11 5.66 1 15 3 13 HIFN 24 2 5 1 3 HIL4_CD 5-10 1 6 4 14 MIL4 25-30 2 5 9 4 HIV1 8 1 5 5 15 PCG18 27.20 2 8 3 5 RB 10-15 1 6 6 16 HIL6_T 28 2 5 10 6 PCG16 11.32 1 11 3 17 PCG13 28.93 2 7 3 7 PCG17 11.92 1 6 3 18 HBV 30.41 2 8 11 8 HCV_NS3 14 1 8 7 19 PCG15 30.78 2 10 3 9 NAPIL8 18.5 1 5 8 20 HIL4 30-40 2 6 12 10 HIL2 20 2 5 1 21 GMCSF_W 40 2 6 13 11 GMCSF_Z 20 2 5 2 22 HIL6 71 2 5 14 --------------------------------------

    45. ?? RNA??????:????????????RNA????????? ?????:??CAI??? ????:??Bayes???????

    46. RNA??????(?)???? ?????????????:-10?-35?,????? ?Gold????????????????-25~21????, ???????????????? ???, 3`?????? ???????????

    47. ??????(?)??????????? ????,?????????AUG????? ?TAA??,?????????,????? ????????RNA????????,?? ??????????,?????????? ??????????????? (?)??? ??,???????? [21,89],[23,95]? [28,93]??????(?)????????? ???,??????

    48. ?: ??????(?)?????? --------------------- ?? F? ?? ????? --------------------- [21,89] 9.7195 0.0012 90.5% [23,95] 10.4115 0.0009 86.4% [28,93] 7.2998 0.0044 73.5% ---------------------

    49. 5`?3`??????? ?????[21,89]??????,????5`? 3`?????????: LES=-10.8036-0.4732*G5-1.8649*G3 (1) HES=-17.1970+0.1559*G5-2.6214*G3 (2) ?E=HES-LES ???G5??5‘?-30~39??(???[21,89]) ????????,G3??3‘?30 ~ -39??? ???????,?????:??E<0?,?? ??????;??E>0?,?????????

    50. 5`????? 5'?????: LES5=-2.4489-0.9339*G5 (3) HES5=-0.6790-0.4918*G5 (4) ???F=5.8383,P=0.0254<0.05,??? ???:59.1%

    51. 3'?????: LES3=-0.0535*G3^2-1.0971*G3- 6.7433 (5) HES3=-0.2130*G3^2-5.6572*G3-37.9814 (6) ???F=9.4318, P=0.006,?????? 68.2%?

    52. 5`?3`??? ????????????,??????, ??????; LES5<HES5 LES3<HES3 ????????????G5,G3??? ???: G5=-4.0 (Kcal/mol) (7) -17.21=G3=-11.38 (kcal/mol) (8)

    53. SD???ATG?TAA??????????(?)???? ?:SD???ATG?TAA??????????????? ----------------------------- Class AUG SD TAA Class AUG SD TAA ----------------------------- 1 3 0 0 2 1 1 0 1 0 3 0 2 0 0 0 1 1 3 3 2 1 0 0 1 0 3 0 2 3 0 0 1 0 0 3 2 0 0 0 1 0 3 0 2 3 0 0 1 2 0 0 2 0 0 0 1 3 0 0 2 1 0 0 1 0 0 0 2 1 3 0 2 0 2 3 2 1 0 0 2 0 4 2 2 3 3 0 -----------------------------

    54. ??SAS????,AUG,SD?TAA ? ????????????????(?)? ?????????,???????? ????,??????????:AUG, SD?TAA???0?

    55. ?????????(?)???? ????5`?3`???????? ??(?)????,??Goldkey?? ?????:X1,X2,...,X30;Y1, Y2,...,Y30??????????? ??Xi?Yj?????900?????(?) ?????,????:?8???,P???, ?????

    56. ?:5'?3'??????????????(?)???? ------------------------------ 5‘?? 3’?? F? ?? ????? ------------------------------ X1 Y3 5.4572 0.0362 73.3% X3 Y3 3.0462 0.0851 73.3% X4 Y3 3.0686 0.0839 73.3% X9 Y3 3.2001 0.0769 73.3% X10 Y2 3.1687 0.0785 80.0% X10 Y3 3.4554 0.0653 66.7% X11 Y3 3.0782 0.0834 66.7% X12 Y3 2.9887 0.0885 66.7% ------------------------------

    57. ???????: P???0.05????,?Y3? P???(?X1=1), ?????????: LEC3=-0.44192+30.73696*Y3 (9) HEC3=-2.35737+70.99093*Y3 (10) P=0.0362,???????????????? ???: Y 3= 0.04758,???????3`?? 3????(??TAA)?????????????

    58. SD????????ATG?? ???(D)??(?)???? ????????????,??D????,? ?,????? 1?????????,???? ????: LED=-4.4464+1.1273*D (11) HED=-3.1267+0.9453*D (12) ???F=1.2325,P=0.2801,??????59.1%, ??,??????(?)???D??????? ??1????,D??8±3????????

    59. ?????????????? ??????,????X6,G5?G3????? ????: LESC=-13.6401+12.8546*X6-0.3612*G5-2.0377*G3 (13) HESC=-21.8205+16.4293*X6+0.2990*G5-2.8423*G3 (14) ???F=6.8386,P=0.0029,???22??? ??????(13)?(14)?????????? ???:22?????????1????? ? ?????????:??1???????? ?5`????????

    60. ?:22?????????? ----------------------------------- No. LESC HESC DC OC No. LESC HESC DC OC ----------------------------------- 1 18.4134 19.8864 2 1 12 19.1358 19.2885 2 2 2 19.5331 18.9596 1 1 13 28.6516 36.1672 2 2 3 6.6124 2.3394 1 1 14 14.4364 15.8918 2 2 4 12.1912 10.8165 1 1 15 18.9552 19.4380 2 2 5 4.4814 0.8667 1 1 16 13.8560 14.7747 2 2 6 19.6776 18.8400 1 1 17 18.5578 19.7668 2 2 7 18.1501 15.0622 1 1 18 22.2221 26.1855 2 2 8 18.4046 14.9546 1 1 19 18.9552 19.4380 2 2 9 5.2970 1.7473 1 1 20 19.4498 20.2457 2 2 10 18.3370 22.4037 2 2 21 18.6168 22.9754 2 2 11 26.5447 27.6698 2 2 22 18.0869 19.4216 2 2 -----------------------------------

    61. ???????? ?:4????????? ----------------------------- No. Name G5 G3 X6 Level OC DC ----------------------------- 1 HCV_L -4.8 -11.4 0.22918 < 10 1 1 2 HCV_W -4.8 -12.8 0.22918 11 1 1 3 JSNA 1.0 -14.0 0.58962 60 2 2 4 TNFA -6.5 -14.9 0.26419 30 2 2 -----------------------------

    62. ???? ???,???:pBV220??????????? ???? ????,13:126-133;1997? ???,???:pBV220??????????? ??????? ??????,7:149-151,1996? Li Wuju, Wu Jiajin: GeneDn: for high-level expression design of heterologous genes in a prokaryotic system Bioinformatics 14:884-885,1998?

    63. ??????? ??Ricin-A??E.coli ??????? ?,?????????(????=20%) ??? ??? ????:?????? ????,1998,14(1):33 ?FKBP12?E.coli????????,? ????????(????=20%) ??? ??? ????:?????? ???????, 2000,16(3):322

    64. ?SCF?E.coli ????????,?????????(????=30%) ????,???? ?????????????????pBVIL1, ???5`?3`???????,??????? ????????????,???????? ?,????????????20%??,?? ??????????????????, 2001,17(3):231

    65. ?????????,???NMDA??????E.coli????????,?????????,??????????6%???29%??????????,2002,???? ????:??????????,??????Insulin,?????NATO??,?????????15%??,????????20%??,?????,??????????????:????????,??????????,????????????????? ???????????:???????,??????,???????

    66. ??:???? ?????????? ???(Yeast system)????? ?????:???????????, ???????,????????????????? ????????????????? ????

    67. ??????? ??????: ???????Chou-Fasman?Garnier?,????????Garnier?????? ??78%??,??80%? ??????: ????,????? ??:????????????????? http://www.expasy.org/

    68. ????? ????????? ?????,????????? ???????,??????????? Maximum parsimony method (Minimum evolution method) Distance methods (Neighbor-joining methods) Maximum likelihood approach http://evolution.genetics.washington.edu/phylip.html

    69. ?????????????? ??????:???????????????,??,??????????????: ?????????????????? ?????????????? ?????????????

    70. ???? ?????: GeneScan,Geneie,… nc RNA ???? ncRNA????????? ncRNA?????????

    71. ncRNA????????? ???????????ncRNA????? ???????????,???????? ?,??????ncRNA??????????? ?????,??????,????????? ??????,??????????????? ??????,?????????ncRNA??? ???????,?????????????? ???????????????,?????? ?????????,??,????????? ??

    72. ????????????? ?????????ncRNA???????? ????????,????????????? (??)???????(??)?????? ?,??,????????????ncRNA?? ??????????????,?????? ?:?????????????????? Eddy?????RNA???????????

    73. ncRNA????????? ????????????????? ?????,?????????ncRNA? ?????,?ncRNA????????? ?????????????????:? ??????????????????? ??????????????????

    74. ?????? ????????????ncRNA??? ?????,?????????,???? ncRNA?????????????????? ???ncRNA??????,??????,? ???ncRNA??????

    75. ?????? ???????????????????:? ??????????ncRNA?????(???)? ??????????(???),???????? ?????????ncRNA??,???????? ?,?????????????????????? ??????????????????,????? ??????????????????????? ?,??,??????????????????? ?,????????????ncRNA?????? ?,????????,????????????

    76. ???????? ?????ncRNA????????????,? ????????????,??????????? ????,??????,Rivas?Eddy?????? ?ncRNA???????,??????QRNA??? ????????????????,??????? ???COD?ncRNA????RNA?????? OTH,???????????,????????? ?? Bayes????,?????????????? ????????ncRNA?????????

    77. ?????????????? ??????????????,???????? ??????????ncRNA???????,???? ???????,???????????“??”?? ???,??????????,?????????? ?(ORF,tRNA,rRNA?);??,???????? ??;??,??????????;??,????? ??????????,?????ncRNA?????? ?????,??????????????

    78. ?? ??????????ncRNA??? ????,?????????????? ?????????????????? ????????,???????? ncRNA???????,??????? ?????

    79. ????????????? ???????????????? ?????????????? ?????????????? ?????????????? ?????????? ???:??????????? ?????????,26:73, 2002

    80. ???????????????????????

    82. ???????,???????? ??????????????????? ???,??????????????? ????,?????????????? ??????????????????? ?????,??????????,?? ?????????????????? ?,????????????????? ?????????,????????? ??????????????????

    83. ??????????????

    84. ?????????? Lukashin(2001)?????????????? ???????:????17??????????? ????????100,?????????2.5???? Welsh(2001)???????????????? ??????????????250,????1243?? ??????????????????? Perou(1999)???R/G????,???26???? ?????,?????????????3??,?? ??1247??????????????,????? ?????????????????

    85. ???????????????????, Xing(2001)?????????????????? ?????CLIFF,??????:???????? ????,?????????????????? ?,???????,????????,????? ????????????????,?????? ?,???????????????????Xing? ???????,???????????????, ?????????????????????,? ?,?????????????????????, ?????,?????????????????? ??????

    86. ???????????????,?? ????????????,??????t-? ????????????????????? ?,??????????????????K- ??????????????,?????? ??????????????SamCluster,? ??????????????????

    88. ??,?????????????????,? ???????????????????????? ???????????????????????? ????????????????,??????? ??,????????????,???????? ??????????;??,?????????? ??????????????????????,? ???????????????????????, ????????????????;??,???? ???????????????????????? ??????????

    89. ?????????????????? ?,??????????????????, ?????,?????;??,?????? ????????????????????, ????????????????,??? Fisher?????????Monte-carlo???? ???????????????,????? ????????,?????????,?? ????????????????????? ??,??,??????????????? ????????????????,???? ?????????????

    90. ???? ???????? ????????

    91. ?????

    92. ??????? ??????????Samcluster?? ?,???????????? ,??? ??????:COLON? OVARIAN ? LEUKEMIA72?LEUKEMIA38 ?

    93. 1?COLON:????????2000?? ??62???,???22?????, ??40?????????? 2?LEUKEMIA72: ????????6817 ????72???,???47???? ??????(ALL),??25??? ???????(AML)?

    94. 3?LEUKEMIA38: ????????6817????38???,?38????,? 27??????????(ALL)?11 ?????????(AML), ????LEUKEMIA72??? ?? 4?OVARIAN: ????????7129???? 36???,?36????,?27????? ??5??????4???????????

    95. ??????(CV)

    96. ?????? 1?????????????,???? ????????????????? ????(gmin)???,?????? ?????????,??????? ?????????gmin????,? ???????????????? ?,??????????????

    97. 2??????????,????????? ??????????????(???? ?),??????????????? ?,?????????????,??? ?????????????? CV=[cv1, cv2, …, cvm]’ ?MCV?SCV??????????????

    98. t-??

    99. ???? ??,????????,???? ?????????????,???? ??????????????,??, ???????????

    100. 1?????? ?????,?????????? ??,????????????,?? ???????0,???1?

    101. 2????????? ????????,??????? ????????,??n??????? ?????,???????????

    102. 3????? ???n?????n??,???? ?????????????????? ?,?????????,?????n? ?????n-1?,???n-1?????? ?????,???????,??? ?,???n????1????

    103. ????????(?????)? ??????,????????6?? ?:???????????????? ?????????????????, ?????????????????? ?Samcluster???,???????? ??

    104. ???????????????????

    105. ???? 1?????????????????????? ????????????,???????? ??????????????????????? ???????????????,??????? ???????????????,??????? ????????,?????,????????? ???????????????(??????? ????????),?????,??????? ?????????????????(????? ??????????)???,???????? ??????????? CVth = MCV+Ci×SCV

    106. 2???????????????????(???? ????),????????????????? ?????????,??????????? ??,??,??t-?????????????, ?????????????????,????? ??????,????????????,???? t-????,????????????????? ????(???P=0.01?0.05?0.1?),??? ??????????????????,???? ?????????,??????????,?? ?????,????????????????, ????????????????

    107. ???????? ???P?????,????????? ???Ci??,??????,??????? ?????????,??????????? ???Sn×n??????????????? ????????????????????? ???????????????????? ?,??????????????????? ??????????,?????????? ????????

    109. ???? ??Matlab??????,??? ???????????????? Samcluster,

    111. ??

    112. ??????????????? ??????????

    113. ????????????? ????????

    122. ????D?????,?CVi???? [0.5,1.0]?,????????????, ??,??????,?CVi????,??? ????????????????;?CVi? ???,????????????????? ?????,??P?(0.01,0.05?0.1)??? ????????????????????? ???,???0.05?0.1??????

    124. ??

    125. ?? ????????,?????????? ?????????????Samcluster,?? ????????????t-???????? ??????????????,?????? ???????,????????????? ????????????????4???? ??????,????,????????? ????????????????????? ??,?????????????????? ??(???????)???????

    126. ?CLIFF?????????????????

    128. ????? 1????????:COLON 2?Fisher????????

    130. ???????? 1?????? 2?t-?? 3????????P? 4?Monte Carlo???? 5??????? 6???????

    131. ?????????? ????????????????,????? ????????????????????,??? ??????????????????,????? ???????????????,???????? ???????,??????,????????? ????????????,??,???????? ????????????????????,??? ??????????

    133. ????

    134. ??

    135. ????????????

    136. ??t-????????????????

    137. ??P???????????

    138. ??Monte-Carlo????????????

    139. ????????? ???????

    140. ??????????????? ??????????,????????? ??????,??????????;??,? ?????????,?????2000????? ??????,???????,??????, ???????????,??????????: ?????T-??,??P???,??????? ??,?????????,???????,? ????????????,????????? ??(??)?????,?????????

    141. Monte-Carlo????????????? ??????????,??,?????? ?:?????????,????????? ??????,??????,??????? ????????,??,????????? ??,?????????????????? ??,?????????????????? ?,?????????????????,? ?,?????????????,????? ???:??????????????,?? ?????,????????;?????? ?,?????????????????

    142. ?? ????????,????Fisher??? ????????????????????? ??????????Tclass, ???????? ?????????Tclass?????, ??? ?:?????????????????? ????,??????????,????? ??????????????,???,?? ????????????,??????? ??

    143. ???? ??,?????????,????????Bayes? ??????????????????????????? ?,???,?Tclass???,??????????? Bayes????,?????????,????:Fisher? ?????????????Bayes??????????? ?,????Fisher??????,??????????, ?????????:1????????????????? ??????,???????,?Fisher???????? ?????????;2?Fisher????????????? ????????,??????,??????????? ?????????????,????????????? ?,???????????

    144. ?? ??Tclass?????????,?? ?????????????????? ?,???????????????? ?????,???????????? ?????????????????? ???????????????,?? ?????

    146. ????? ??????????????????? ??????,????307???????? ????,??????16????179?? ?,???11????????,???11?? ????????????,??,????? ??????????Samcluster????? Tclass????????

    147. ??Samcluster???????

    148. ??Tclass???????

    151. ???? ??:???????????????? ?????:MatLab?SAS? ???????:Blast?Mfold?GOR?… ???Nucleic Acid Res.Web??

    153. BioSun???? ????:????????????????? ????:????????????????? ??,???????????,?? ????????????????? ????????????????? ?????????,??????? ??????????????

    155. Goldkey???????????,?????4??? ????Pascal????,??????????64K,???? ?????????????,????????????? 32K,??????????????? ????????,Goldkey????????????,??? ?????????????,?????????????? ?????????? ?????,Goldkey??????????????????? ??,???????????????? ????????????,????????????,?? ??????????????Goldkey?????????

    156. BioSun????

    157. BioSun???????

    158. ??????????? ???????? ?????????? ??????? BioSun????? GenBank?EMBL?FastA?????

    161. ???? ????:????(????)?????? ?????????????(??? ?)? ????:???????????????? ???????????????? ????????????????? ???????????????? ??????? ??:PCR?????????????????

    167. ??????? ?????? ??????(MW,PI,…) ????? ????? ????????? ???????????? ????????? ???????????

    179. ????????? X:????? N:????? {P}:?P??????? [ST]:???S,???T [ST](2):??????????[ST] X(2,4):?2?3?4??????????

    182. DNA?RNA???? ?????? DNA???? ??????????? PCR?????PCR???? DNA???????? RNA????????? ????????RNA??????? ?????????? ??????????

    190. ??????? ????????????? ??cDNA??????? ??????????????

    194. ??

    195. ?? Tel: 66931324 Email: liwj@nic.bmi.ac.cn http://www.biosun.com.cn

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