IPA 사용자교육 Consulting 팀 _ 서지혜 2018. 11. 본문서의모든컨텐츠는저작권법의보호를받는저작물로별도의저작권표시또는다른출처를명시한경우를제외하고는 ( 주 ) 인실리코젠에저작권이있습니다. 저작권표시또는기타소유권표시를삭제해서도안되며, 당사와의협의또는허락없이무단복제, 변경, 배포를금지합니다. 저작권관련문의사항이있으시면 bc@insilicogen.com 으로연락바랍니다. c 2018 INSILICOGEN, INC. ALL RIGHTS RESERVED.
Biomarker Analysis
Introduction
QIAGEN Workflow c 2018 INSILICOGEN, INC. ALL RIGHTS RESERVED. 4
IPA 로무엇을할수있을까? c 2018 INSILICOGEN, INC. ALL RIGHTS RESERVED. 5
Ingenuity Knowledge Base c 2018 INSILICOGEN, INC. ALL RIGHTS RESERVED. 6
Ingenuity Systems Over 15 years Joined the QIAGEN family as the bioinformatics center of excellence Ingenuity has been cited in >16,000 scientific publications to date The goal is to help life science researchers get biological insights from their data quickly and reliably User base reflects strong adoption in research community Top pharmaceutical companies Large biotechs Academic and government research labs Copyrightc Insilicogen,Inc. 2018. All rights reserved. 7
IPA 로무엇을할수있을까? 관심있는 gene/protein/compound는어떤일을할까? 관심있는타겟은어떤 compound와결합할까? 대상단백질을억제하거나활성화시키면어떤세포과정에영향을미치게될까? 관심있는 protein의 upstream이나 downstream의타겟은무엇일까? Microarray 데이터로세포기능변화나, pathway, toxicology에서어떤변화를보여줄수있을까? 관심있는질병에관련된유전자는어떤것이있을까? 어떤단백질이약효검정을위한바이오마커로사용하기좋을까? c 2018 INSILICOGEN, INC. ALL RIGHTS RESERVED. 8
c 2018 INSILICOGEN, INC. ALL RIGHTS RESERVED. 9
지원하는種 (Species) Human, Mouse, Rat in full content human/mouse/rat orthologs를다른식별자에맵핑하기위해서 HomoloGene을이용 ( 추가적인종은 human, mouse, rat에특이적으로붙어야지원가능 ) Arabidopsis thaliana Bos taurus (bovine) Caenorhabditis elegans Gallus gallus (chicken) Pan troglodytes (chimpanzee) Danio rerio (zebrafish) Canis lupus familiaris (canine) Drosophila melanogaster Macaca mulatta (Rhesus Monkey) Saccharomyces cerevisiae Schizosaccharomyces pombe c 2018 INSILICOGEN, INC. ALL RIGHTS RESERVED. 10
Ingenuity Publications Discovery 질병프로세스를이해하고, 타겟을증명하고확인 Biomarkers 새로운바이오마커탐색, 질병프로세스에서그들의역할에대한이해 Toxicology 잠재적인독성메카니즘을밝힘. Pharmacogenomics 치료제에차등적인반응에대한통찰력을확보 Copyrightc Insilicogen,Inc. 2018. All rights reserved. 11
Ingenuity Publications Peer-Reviewed Research Articles Citing IPA Over 16,000 Citations in Peer Reviewed Publications! Copyrightc Insilicogen,Inc. 2018. All rights reserved. 12
Ingenuity Publications Copyrightc Insilicogen,Inc. 2018. All rights reserved. 13
기능및특 장점 큐레이션된데이터베이스 Ingenuity Knowledge Base 는통계및생물, 화학계통의박사연구원들에의해큐레이션된데이터 구조화된 DB 에 환자표현형메커니즘 질병메커니즘 세포메커니즘 분자메커니즘 시퀀스메커니즘을모두연결지어분석 주기적인업데이트 Copyrightc Insilicogen,Inc. 2018. All rights reserved. 14
기능및특 장점 데이터베이스통합 Gene View, Chem View, Disease/Function View Description GO Annotations Human, Mouse, Rat details Database Information (Gene, RNA, Prot.) Functional roles Mutant Information Modifications and regulation Disease Expression and Localization Physical interactions Literature entries Additional findings Summary 페이지 - Genes 과 Chemical, Disease, Function 에관련된여러정보를보기쉽게정리 정보를효율적으로취득 - 다양한생물정보데이터베이스를통합 Copyrightc Insilicogen,Inc. 2018. All rights reserved. 15
기능및특 장점 간편한데이터업로드 Microarray chip, Entrez, UCSC 등의다양한데이터베이스의 Gene ID 를통합, 인식 Fold change, P-value, intensity, Ratio 인식 Input 파일포맷 : Excel - Batch 기능을이용하여여러파일을동시에업로드가능 -Fold change, RPKM/FPKM, P-value, Ratio, log 값등을인식하고분석함 - Output 파일포맷 : JPEG, GIF, PNG, HPML, SVG, EPS, EMF, BMP, PDF, TIFF, Text, Excel Array identifiers Gene identifiers Protein identifiers Metabolomic identifiers Copyrightc Insilicogen,Inc. 2018. All rights reserved. 16
기능및특 장점 실험 dataset 분석 Canonical pathway Upstream Regulator Downstream Effects Analysis 유전자셋이가장영향을줄것같은 pathway 유전자셋을조절하는 Regulator 탐색 영향을줄수있는 Function & Diseases Copyrightc Insilicogen,Inc. 2018. All rights reserved. 17
기능및특 장점 네트워크분석 Interaction Networks, Build and Overlay tools DB 를통해그린네트워크에실험데이터를 Overlay 패스웨이를실험목적에맞게편집 관심있는유전자에의해이웃하는유전자들이어떠한영향을받을수있는지예측 Pathway Design Copyrightc Insilicogen,Inc. 2018. All rights reserved. 18
기능및특 장점 샘플타입별분석 Core, Tox and Metabolomics Analyses Comparisons MicroRNA tools Copyrightc Insilicogen,Inc. 2018. All rights reserved. 19
기능및특 장점 A. Open-Source Data Analysis Workflow* 예측되는영향과전사조절의방향성예측은포함되어있지않음 B. IPA Data Analysis Workflow Ingenuity Pathway Analysis 의 upstream transcription factors, the micrornamrna Target Filter, directional downstream effects 등의기능들은방향성을예측하는데활용됨 대용량데이터세트와마이크로어레이데이터의분석시간을상당히절감할수있음 Ingenuity Knowledge Base 에의해동의어를검색하는데들이는시간을크게단축할수있습니다. (e.g. ANXA or Annexin 2 ) 즉, 관심있는유전자에대해신속하고정확한연구를가능하게합니다. Copyrightc Insilicogen,Inc. 2018. All rights reserved. 20
기능및특 장점 Table1. 대용량데이터분석시, 능률과걸리는시간비교 ++ 는데이터시각화또는어떤영향을미칠것인지예측까지할수있음. + 는기본적인유전자맵핑기능과테이블로결과제시 +/- 는양면성을띔. N/A 는작업을수행할수없음. Table2. microrna target 분석시, 제공되는결과와걸리는시간비교 한개의 microrna(has-mir-325) 의타겟을얻는데걸리는시간 micrornas 에의한영향을받는패스웨이를규명하는데걸리는영향 Copyrightc Insilicogen,Inc. 2018. All rights reserved. 21
시작하기
Installation https://analysis.ingenuity.com/pa/installer/select c 2018 INSILICOGEN, INC. ALL RIGHTS RESERVED. 23
Interface 메뉴 검색창 Project Manager : 데이터관리 Quick Start : 분석 Tool 포함 c 2018 INSILICOGEN, INC. ALL RIGHTS RESERVED. 24
Simple Data Upload Process IPA 에업로드할수있는파일포맷 Gene ID Sample value 참고사이트 : http://ingenuity.force.com/ipa/articles/feature_description/data-upload-definitions Copyrightc Insilicogen,Inc. 2016. All rights reserved. 25
c 2018 INSILICOGEN, INC. ALL RIGHTS RESERVED. 26
c 2018 INSILICOGEN, INC. ALL RIGHTS RESERVED. 27
Import 파일조건 엑셀파일이나탭으로구분된텍스트파일, CuffDiff 형식의파일 평균값이나, ratio, fold change등은미리계산 (IPA에서는어떤계산도지원하지않음 ) 헤더는 0개혹은 1개여야만함. 첫번째컬럼에 ID를두게되고, 약 100정도의정보를기반으로 ID 유형을결정. 헤더의텍스트를사용하여유형을추측 파일당 observation 지정은 20개만가능 (20sample) Observation 당 8개의 measurement value 사용가능 c 2018 INSILICOGEN, INC. ALL RIGHTS RESERVED. 28
Upload Dataset c 2018 INSILICOGEN, INC. ALL RIGHTS RESERVED. 29
Upload Dataset c 2018 INSILICOGEN, INC. ALL RIGHTS RESERVED. 30
발현값계산방법 c 2018 INSILICOGEN, INC. ALL RIGHTS RESERVED. 31
Simple Data Upload Process Copyrightc Insilicogen,Inc. 2018. All rights reserved. 32
Core Analysis
Core Analysis c 2018 INSILICOGEN, INC. ALL RIGHTS RESERVED. 34
Core Analysis Toxic Metabolomics c 2018 INSILICOGEN, INC. ALL RIGHTS RESERVED. 35
Core Analysis Core Analysis Type Description Required Dataset Measurement Type Identifier Types Supported Expression 데이터셋의유전자나단백질의발현변화의차이에따라가장변화될가능성이높은신호및대사경로, upstream regulator, 분자상호작용네트워크및질병및생물학적기능에대해서빠르게파악 Expression (Expr) Gene / Protein Tox 화합물또는독성물질의독성및안전성평가하고데이터셋의유전자또는단백질의발현변화에의해유된관련독성표현형및임상병리학적으로이해 Expression (Expr) Gene / Protein Metabolomics metabolomics 데이터셋의대사산물농도변화로부터세포생리학및대사에대한생물학적통찰력을얻는데필요한중요한컨텍스트를제공 Expression (Expr) Chemical. Can include Gene / Protein identifiers. c 2018 INSILICOGEN, INC. ALL RIGHTS RESERVED. 36
Create Expression Analysis c 2018 INSILICOGEN, INC. ALL RIGHTS RESERVED. 37
Create Expression Analysis c 2018 INSILICOGEN, INC. ALL RIGHTS RESERVED. 38
Create Expression Analysis c 2018 INSILICOGEN, INC. ALL RIGHTS RESERVED. 39
Create Expression Analysis c 2018 INSILICOGEN, INC. ALL RIGHTS RESERVED. 40
Create Expression Analysis c 2018 INSILICOGEN, INC. ALL RIGHTS RESERVED. 41
Create Expression Analysis c 2018 INSILICOGEN, INC. ALL RIGHTS RESERVED. 42
Create Expression Analysis c 2018 INSILICOGEN, INC. ALL RIGHTS RESERVED. 43
Create Expression Analysis c 2018 INSILICOGEN, INC. ALL RIGHTS RESERVED. 44
Create Expression Analysis c 2018 INSILICOGEN, INC. ALL RIGHTS RESERVED. 45
Create Expression Analysis c 2018 INSILICOGEN, INC. ALL RIGHTS RESERVED. 46
Create Expression Analysis c 2018 INSILICOGEN, INC. ALL RIGHTS RESERVED. 47
Core Analysis Pathway Analysis 유전자발현에기반하여이미밝혀져있는 pathway 를보고 activation 이나 inhibition 을예측 MAP overlay 툴을이용하여데이터셋의값을이용하여 pathway 방향성예측 Upstream Regulator Disease and Function Regulator Effects Network c 2018 INSILICOGEN, INC. ALL RIGHTS RESERVED. 48
Core Analysis c 2018 INSILICOGEN, INC. ALL RIGHTS RESERVED. 49
Z-score c 2018 INSILICOGEN, INC. ALL RIGHTS RESERVED. 50
Core Analysis c 2018 INSILICOGEN, INC. ALL RIGHTS RESERVED. 51
Canonical Pathway c 2018 INSILICOGEN, INC. ALL RIGHTS RESERVED. 52
Core Analysis Pathway Analysis Upstream Regulator 발현을변화를유도하는 upstream regulator 규명 Activation state 예측 Disease and Function Regulator Effects Network c 2018 INSILICOGEN, INC. ALL RIGHTS RESERVED. 53
Upstream Analysis c 2018 INSILICOGEN, INC. ALL RIGHTS RESERVED. 54
Upstream Analysis c 2018 INSILICOGEN, INC. ALL RIGHTS RESERVED. 55
Upstream Analysis Regulator 당데이터셋내의 target molecule Regulator 하위의내데이터셋유전자수 ( 네트워크내의 regulator 수 ) c 2018 INSILICOGEN, INC. ALL RIGHTS RESERVED. 56
Upstream Analysis c 2018 INSILICOGEN, INC. ALL RIGHTS RESERVED. 57
Core Analysis Pathway Analysis Upstream Regulator Disease and Function 유전자발현에기반한생물학적인효과를예측 - 예 : Cell cycle 증가, apoptosis 감소 Regulator Effects Network c 2018 INSILICOGEN, INC. ALL RIGHTS RESERVED. 58
Disease & Functions c 2018 INSILICOGEN, INC. ALL RIGHTS RESERVED. 59
Disease & Functions c 2018 INSILICOGEN, INC. ALL RIGHTS RESERVED. 60
Disease & Functions c 2018 INSILICOGEN, INC. ALL RIGHTS RESERVED. 61
Disease & Functions c 2018 INSILICOGEN, INC. ALL RIGHTS RESERVED. 62
Disease & Functions c 2018 INSILICOGEN, INC. ALL RIGHTS RESERVED. 63
Regulator Effects Pathway Analysis Upstream Regulator Disease and Function Regulator Effects 예측된 Upstream regulator, DEG 혹은 biological processes 로부터 pathway interaction 을 modeling Network c 2018 INSILICOGEN, INC. ALL RIGHTS RESERVED. 64
Regulator Effects c 2018 INSILICOGEN, INC. ALL RIGHTS RESERVED. 65
Regulator Effects c 2018 INSILICOGEN, INC. ALL RIGHTS RESERVED. 66
Regulator Effects c 2018 INSILICOGEN, INC. ALL RIGHTS RESERVED. 67
Networks Pathway Analysis Upstream Regulator Disease and Function Regulator Effects Network 방향성없는유전자들을가지고상호작용하는지도를예측 c 2018 INSILICOGEN, INC. ALL RIGHTS RESERVED. 68
Networks c 2018 INSILICOGEN, INC. ALL RIGHTS RESERVED. 69
Networks c 2018 INSILICOGEN, INC. ALL RIGHTS RESERVED. 70
Comparison Analysis
Comparison Analysis c 2018 INSILICOGEN, INC. ALL RIGHTS RESERVED. 72
Comparison Analysis c 2018 INSILICOGEN, INC. ALL RIGHTS RESERVED. 73
mirna Analysis
mirna Database c 2018 INSILICOGEN, INC. ALL RIGHTS RESERVED. 75
mirna Naming and Mapping c 2018 INSILICOGEN, INC. ALL RIGHTS RESERVED. 76
mirna Analysis c 2018 INSILICOGEN, INC. ALL RIGHTS RESERVED. 77
Biomarker Filter
Biomarker Analysis IPA 에서 biomarker 란? 체액혹은조직 / 세포 / 세포주에서발견할수있으며특정한조건혹은질병이나진단치료의목적으로 볼수있는 phenotype 에서정상 / 비정상적인을판단할수있는생물학적분자단위 IPA-Biomarker 분석은생물학적인기준에의해후보들을필터 Species Tissues and Cell Lines Biofluids Diseases Clinical Biomarkers Biomarker 분석에서는 network 나기능분석, canonical pathway 는제공하지않음 여러데이터셋끼리 biomarker 비교가가능
Biomarker Analysis 질병진단및예후, 질병진행지표, 약물효능및안전성지표, 치료에대한환자반응지표등의특정용도의바이오마커후보들을필터링할수있음. c 2018 INSILICOGEN, INC. ALL RIGHTS RESERVED. 80
Biomarker Analysis Biomarker Comparison Analysis c 2018 INSILICOGEN, INC. ALL RIGHTS RESERVED. 81
Biomarker Analysis Biomarker Comparison Analysis c 2018 INSILICOGEN, INC. ALL RIGHTS RESERVED. 82
Biomarker Analysis c 2018 INSILICOGEN, INC. ALL RIGHTS RESERVED. 83
Biomarker Analysis c 2018 INSILICOGEN, INC. ALL RIGHTS RESERVED. 84
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