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보고서요약문 Ÿ Ÿ Ÿ Ÿ Ÿ Ÿ - 1 -
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정책연구용역사업연구결과 - 3 -
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Ÿ Ÿ Ÿ - 13 -
: TI=(Asthma or "chronic obstructive pulmonary disease" or "idiopathic plmonary disease") OR AB=((Asthma or "chronic obstructive pulmonary disease" or "idiopathic plmonary disease") AND (MEDICATION or DRUG or Therapy)) AND AD>=(19960101) AND AD<=(20151231) - 14 -
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Ÿ Ÿ - 17 -
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IPF registry ecrf (http://ipf.crf.kr) - 19 -
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Ÿ Ÿ Ÿ Ÿ - 22 -
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Ÿ Ÿ - 24 -
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α αα β α β α α α α - 28 -
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Ÿ Ÿ Ÿ 임상역학정보 CDE 확립 Ÿ Ÿ Ÿ Ÿ Ÿ - 34 -
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± - 39 -
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β - 43 -
Ÿ - 44 -
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학술연구개발용역과제시행계획서 [ 다년도과제 ] - 49 -
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F 1) 자원의확보 저장및정도관리등모든절차는본과제에서수립한 SOP 를반드시적용하여야함. 2) 대상군의추적자원수집계획이포함되어야하며, 추적자원은기본인원에포함된질환자의추가내원및추가진단검사등을통해확보된추가실물자원 ( 혈액, 혈청, DNA 및연구자가제시한특화자원등 ) 과치료예후, 합병증여부, 임상검사결과등을뜻함. 또한해당자원의연구에적절한대조군을선정하고, 동일한조건으로확보하여야함. 3) Genomics, transcriptomics, epigenomics 는필수. Proteomics, metabolomics, metagenomics 중한종류이상선택. 수집자원 ( 실물자원및정보등 ) 의질이 omics 연구에적합하다는것을객관적으로증명할수있는수준의 omics 데이터를산출하여야함. 과제계획서에수집자원수, 임상정보수, omics 연구대상자원의수및 Omics 정보수등구체적인계획을제시하여야함. Omics 데이터에대한 QC/QA 방안의작성및해당데이터에대한국내외데이터비교검증자료의확보계획이계획서에포함되어야함. - 53 -
계 - 54 -
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Ÿ Ÿ Ÿ Ÿ Ÿ Ÿ Ÿ Ÿ * Ÿ Ÿ Ÿ Ÿ Ÿ * 질환자원의수집및오믹스분석을수행할수있는기관간컨소시움을활용해야함, 컨소시움의원활한운영을통해연구과제를성공적으로달성할수있도록컨소시움참여기관, 발주부서의과제담당자 1 인, 관련분야전문가등으로구성된운영위원회를구성 운영해야함 - 56 -
* 주관연구기관및컨소시움참여기관은해당질환에대한전문성을확보하고해당질환자의진단 치료를직접수행하고있는기관, 인체자원및정보관리기관및오믹스분석기관으로구성하고, 본과제의목적과공공자원화에동의하는기관으로한정함 < 센터컨소시엄구성예시 > * 추적자원은질환자의지속적인내원과진단검사등을통해확보된추가실물자원 ( 혈액, 혈청, DNA 등 ) 뿐아니라, 치료예후, 합병증여부, 임상검사결과등과같은 정보를모두포함함. - 57 -
* 자원과함께수집되는정보종류에따라 ( 예, 정보의생산에고비용이발생하는 MRI, CT 정보등이함께수집되는경우 ), 혹은발병률이낮거나주로어린아이등에발생하여자원공여자 ( 기증자 ) 의확보가어려운경우등은년차별로수집목표의몇 % 까지수집할지연구자가제시하여생물자원은행과와협의 조정할수있음 - 58 -
해당자원 ( 정보포함 ) 의종류, 확보 관리 SOP 및기탁되는자원의공공자원화에관련된모든사항 ( 예, 저장규격, 수량, ID체계, 기탁비율등 ) 등은발주부서 ( 생물자원은행과 ) 와협의하여결정함. [ 기타사항 ] 인체자원분양심의위원회 의심의받을당시연구계획서에기술된연구계획일정에따라연구가종료됨과동시에 raw data 는즉시국립중앙인체자원은행에기탁하여야하며, 이경우데이터의일반공개는연구자가학술논문등을발표한다음공개하는것을원칙으로함 ( 다만, 연구자가데이터공개등을의도적으로지연시킨다고판단되는경우는 인체자원분양심의위원회 심의를거쳐공개등을할수있음 ). - 59 -
F - 60 -
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(ex) 순천향대학교부천병원첫번째제공자식별자 : ILD_BC0001 기관명 ( 추후참여기관변동에따라기관코드추가배정예정 ) 기관코드 - 72 -
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* Total Cell count = 25 구획세포수 x Total volume x 2 x10 4 * Viability(%) = 25 구획내살아있는세포수 25 구획내전체세포수 100-76 -
Ÿ Ÿ - 77 -
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μ μ - 79 -
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μ μ μ μ μ - 85 -
μ Ÿ Ÿ - 86 -
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Volume(μl) of TE Volume (μl) of RNA (2ng/ul) 0 100 50 50 90 10 98 2 100 0 Ÿ - 88 -
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그림. GenomeStudio 를이용한 HT-12 chip 분석이미지 - 92 -
표. Expression Chip 데이터의기본구조 Gene S1_Avg_signal S1_Det_P-val S2_Avg_signal S2_Det_P-val S3_Avg_signal S3_Det_P-val 7A5-2.86 0.697 4.39 0.188 9.83 0.030 A1BG 8.56 0.018 7.91 0.055 7.05 0.195 A1CF 6.05 0.018-1.91 0.698-0.53 0.556 A26C3-2.94 0.819-1.46 0.550 5.00 0.146 A2BP1-0.46 0.640-3.20 0.813-1.23 0.660 A2LD1 44.95 0.000 53.63 0.000 67.60 0.000 A2M -4.27 0.781 70.60 0.000 47.01 0.000 A2ML1-0.22 0.505-5.00 0.829-3.49 0.742 A3GALT2 0.26 0.430 1.46 0.261-2.33 0.706 A4GALT 89.29 0.000 256.66 0.000 137.59 0.000 A4GNT 14.46 0.016 18.55 0.001 9.06 0.045 AAA1-0.58 0.606 2.20 0.144-0.04 0.381 AAAS 30.53 0.000 32.90 0.000 37.77 0.000 AACS 50.67 0.000 38.50 0.000 29.91 0.000 AACSL 20.30 0.003 22.06 0.000 11.15 0.027 AADAC -0.41 0.517 1.41 0.365 0.14 0.435 AADACL1 285.40 0.000 140.45 0.000 162.26 0.000 AADACL2 3.98 0.197-2.97 0.665-7.31 0.934 AADACL3 4.10 0.192-1.96 0.590-8.04 0.951 AADACL4 7.39 0.073 3.19 0.243 3.58 0.214 AADAT 18.98 0.229 20.90 0.208 20.34 0.131 AAGAB 103.38 0.000 110.58 0.000 133.72 0.000 AAK1 2.58 0.358 3.99 0.352 7.12 0.047 AAMP 177.85 0.000 167.77 0.000 195.49 0.000 AANAT -3.61 0.756-9.15 0.974 0.18 0.431 AARS 1243.02 0.000 1490.21 0.000 1556.55 0.000 AARS2 140.03 0.000 60.11 0.000 63.72 0.000 AARSD1 127.71 0.000 106.99 0.000 134.40 0.000 AASDH 54.25 0.000 73.53 0.000 50.01 0.000-93 -
표. Detection P-value 를기준으로유전자삭제 표. Avg_signal 1 이하의값을 0.05 로변환 - 94 -
표. Detection P-value 를제거한최종데이터양식 표. 기본통계분석결과 - 95 -
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그림. GenomeStudio 를이용한 HumanMethylation450 chip 분석이미지 Ÿ Ÿ - 101 -
표. Methylation Chip 데이터의기본구조 TargetID Chr Position G1-1 G1-2 G1-3 G1-4 G2-1 G2-2 G2-3 G2-4 cg00259849 8 4183880 0.014 0.226 0.303 0.95 0.013 0.21 0 0 cg00322062 15 43032408 0.913 0.921 0.926 0.899 0.872 0.955 0 0.914 cg01270299 19 53099757 0.959 0.953 0.803 0.94 0 0.871 0.924 0.959 cg01591343 6 169857450 0.586 0.92 0.641 0.927 0.953 0 0.907 0.517 cg01600516 17 6904263 0.93 0.928 0.942 0.063 0 0.926 0 0.896 cg04245305 3 195940754 0.022 0.964 0.641 0.908 0.739 0.667 0.925 0.883 cg05176970 17 724273 0.896 0.342 0.941 0.33 0.947 0.027 0.273 0.875 cg08299859 10 13259274 0.18 0.932 0 0.933 0 0.96 0 0.941 cg09462281 19 3191030 0.134 0 0.038 0 0.454 0.92 0.833 0.942 cg10263003 2 235766844 0.941 0.909 0.265 0 0.249 0.92 0.897 0.924 cg10526376 2 1788254 0.943 0.932 0.946 0.952 0 0.936 0.932 0.94 cg11660308 10 127817363 0.92 0.939 0.928 0.915 0.01 0.899 0.912 0.933 cg11935063 13 114161875 0.916 0.943 0.882 0.95 0.914 0.937 0.91 0.951 cg11987751 1 1663860 0.932 0.938 0 0.929 0.93 0.922 0.894 0.949 cg12770425 6 33585071 0.903 0 0.9 0.931 0.921 0.946 0.856 0.916 cg13810332 9 114421433 0.896 0.949 0.886 0.818 0.89 0.887 0.858 0 cg14651435 7 157209551 0.483 0.939 0.029 0.533 0.965 0.954 0.939 0.947 cg15408512 10 135105487 0.949 0.344 0.907 0.939 0.936 0 0.065 0.97 cg15599437 5 40676198 0 0.921 0.941 0.941 0.925 0.947 0.912 0.921 cg16094767 17 821595 0.315 0.676 0.28 0.014 0.759 0.604 0.928 0.38 cg17441804 6 29714059 0.944 0 0.928 0.744 0.916 0.732 0.894 0.806 cg18969004 6 31164743 0.908 0.924 0 0.82 0.926 0 0.961 0.934 cg19249811 10 29747315 0.963 0.942 0.961 0.938 0.933 0.961 0.009 0.967 cg19362774 8 6664522 0.906 0.907 0.904 0.859 0.907 0.847 0.844 0.789 cg20667334 2 236676021 0.964 0.981 0.972 0.974 0.97 0.01 0.972 0.969 cg20720056 10 101910498 0.631 0.005 0.877 0.827 0.612 0.939 0.625 0.892 cg21543103 5 6740855 0.886 0.87 0.887 0.918 0 0.946 0.887 0.939 cg21589417 2 170834853 0.581 0.005 0 0.913 0.944 0.556 0.025 0.954 cg23505044 17 9129824 0 0.933 0.462 0.919 0.429 0.905 0.84 0.908 cg23699809 8 28745972 0.275 0.315 0.519 0.294 0.976 0.256 0.057 0 cg25138752 5 1650942 0.953 0.14 0.853 0.895 0.616 0 0.925 0.845 cg26709433 6 169571488 0.898 0.905 0.9 0.912 0.214 0.949 0.917 0.203 cg27516925 16 90095949 0.884 0.834 0.944 0.92 0 0.915 0.735 0.907-102 -
표. Detection P-value를기준으로유전자삭제 TargetID Chr Position G1 평균 G2 평균 delta Beta T-test TNoM cg00259849 8 4183880 0.373 0.056-0.318 0.18 0.12 cg00322062 15 43032408 0.915 0.685-0.230 0.36 0.12 cg01270299 19 53099757 0.914 0.689-0.225 0.37 0.12 cg01591343 6 169857450 0.769 0.594-0.174 0.49 0.12 cg01600516 17 6904263 0.716 0.456-0.260 0.47 0.12 cg04245305 3 195940754 0.634 0.804 0.170 0.48 0.12 cg05176970 17 724273 0.627 0.531-0.097 0.74 0.12 cg08299859 10 13259274 0.511 0.475-0.036 0.93 0.12 cg09462281 19 3191030 0.043 0.787 0.744 0.0007 0.03 cg10263003 2 235766844 0.529 0.748 0.219 0.48 0.12 cg10526376 2 1788254 0.943 0.702-0.241 0.34 0.12 cg11660308 10 127817363 0.926 0.689-0.237 0.34 0.12 cg11935063 13 114161875 0.923 0.928 0.005 0.78 0.12 cg11987751 1 1663860 0.700 0.924 0.224 0.37 0.12 cg12770425 6 33585071 0.684 0.910 0.226 0.36 0.12 cg13810332 9 114421433 0.887 0.659-0.229 0.34 0.12 cg14651435 7 157209551 0.496 0.951 0.455 0.05 0.12 cg15408512 10 135105487 0.785 0.493-0.292 0.37 0.12 cg15599437 5 40676198 0.701 0.926 0.226 0.37 0.12 cg16094767 17 821595 0.321 0.668 0.347 0.10 0.12 cg17441804 6 29714059 0.654 0.837 0.183 0.45 0.12 cg18969004 6 31164743 0.663 0.705 0.042 0.90 0.12 cg19249811 10 29747315 0.951 0.718-0.234 0.36 0.12 cg19362774 8 6664522 0.894 0.847-0.047 0.13 0.12 cg20667334 2 236676021 0.973 0.730-0.243 0.35 0.12 cg20720056 10 101910498 0.585 0.767 0.182 0.44 0.12 cg21543103 5 6740855 0.890 0.693-0.197 0.43 0.12 cg21589417 2 170834853 0.375 0.620 0.245 0.47 0.12 cg23505044 17 9129824 0.579 0.771 0.192 0.47 0.12 cg23699809 8 28745972 0.351 0.322-0.029 0.91 0.12 cg25138752 5 1650942 0.710 0.597-0.114 0.70 0.12 cg26709433 6 169571488 0.904 0.571-0.333 0.16 0.12 cg27516925 16 90095949 0.896 0.639-0.256 0.29 0.12 (http://compbio.cs.huji.ac.il/scoregenes/scoregenesmanual.html) - 103 -
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