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CPTAC Training, NIH 2018
LinkedOmics: A web-based platform
for cancer multi-omics data analysis,
integration and comparison
01/05/2018
Suhas Vasaikar
suhas.vasaikar@bcm.edu
Dr. Bing Zhang Group
Baylor College of Medicine, Houston Texas
CPTAC WORKSHOP
CPTAC Training, NIH 2018
Multidimensionality of high-throughput data
Experimental Study
GEO data
Public OMICS resource
PDX Samples
Is data accessible?
Is public data available in the usable format ?
With the use of available data, how to understand the relation
between tumor-associated attributes in different platforms ?
How to perform across platform analysis ?
TCGA Cancer cohort
Increase in dimensionality increases complexity
CPTAC Training, NIH 2018
www
Multi-Omics Analysis (Why and How?)
Challenge is how to make genomic/proteomic data available to user and allow them
to perform multi-omics / pan-cancer analysis without difficulty
CPTAC Training, NIH 2018
Platforms
/MS proteomics
Clinical
Methylation
Mutation
CNV
mRNA
RPPA
Proteomics
miRNA
Mutation
Copy number
Gene expression
DNA methylation
microRNA
RPPA/MS proteomics
Clinical data
Discover, compare, and interpret
omics associations
mRNA
Copy
number
Protein
Protein 1
Protein 2
Protein 3
……
……
……
……
……
……
……
……
Protein n
mRNA Protein
LinkedOmics Motivation
TCGA
Pathway
CPTAC Training, NIH 2018
Omics data for 32 cancer cohorts downloaded from TCGA (version 2016_01_28). The platform includes data from methylation (gene level), copy number variation
(focal and gene level), mutation (site and gene level), mRNA expression (gene level), miRNA expression (gene level), RPPA (analyte and gene level) and clinical data
(phenotype) related to primary tumors from 11,158 patients. It also includes mass spectrometry-based proteomics data generated by the Clinical Proteomic Tumor
Analysis Consortium (CPTAC) for TCGA breast, colorectal, and ovarian tumors.
Data Source
CPTAC Training, NIH 2018
LinkFinder
Within- and cross-omics associations
LinkCompare
Multi-omics and pan-cancer analysis
LinkInterpreter
Pathway and network analysis
LinkInterpreter
Pathway and network analysis
LinkFinder
Within- and cross-omics associations
LinkCompare
Multi-omics and pan-cancer analysis
TCGA/
CPTAC
LAML, ACC,
BLCA, LGG,
BRCA,
CESC,
CHOL,
COAD,
COADREAD,
ESCA, GBM,
HNSC, KICH,
KIRC, KIRP,
LIHC, LUAD,
LUSC,
DLBC,
MESO
OV, PAAD,
PCPG,
PRAD,
READ,
SARC,
SKCM
STAD,
TGCT,
THYM,
THCA, UCS,
UCEC, UVM
32 cancer types; 11,158 patients; >1 billion data points
Data Organization and Analysis Modules
CPTAC Training, NIH 2018
Webportal
www.linkedomics.org
CPTAC Training, NIH 2018
www.linkedomics.org
Overview of “LinkedOmics” webportal
Query Panel has 5 steps
Step1: Select Cancer Type
Step2: Select Search dataset, for ex. Mutation
datatype
Step2b: Select Specific Population (optional)
Step3: Select Search attribute, for ex. TP53
Step4: Select Target dataset, for ex. mRNA
Expression (RNAseq) datatype
Step5: Select Statistical Method
Click 'SUBMIT' button
CPTAC Training, NIH 2018
Lets explores some examples
CPTAC Training, NIH 2018
In Prospective Uterine Corpus Endometrial
Carcinoma (UCEC), how clinical phenotype
serous associated with gene expression?
Example1
Search Dataset
Target Dataset
Search Attribute
Cancer cohort
CPTAC Training, NIH 2018
Select the cancer cohort “CPTAC UCEC”
CPTAC Training, NIH 2018
Select “Search attribute” and “Target Dataset”
CPTAC Training, NIH 2018
Select “Statistical test”
CPTAC Training, NIH 2018
CPTAC Training, NIH 2018
Serous phenotype associated with gene expression
View Results
Search history will be shown
New analysis to START
CPTAC Training, NIH 2018
Serous phenotype associated with gene expression
CPTAC Training, NIH 2018
CPTAC Training, NIH 2018
LinkInterpreter
Enrichment analysis
CPTAC Training, NIH 2018
CPTAC Training, NIH 2018
CPTAC Training, NIH 2018
Lets explores more cases
• Case example: Clinical Serous phenotype association with
Proteomics
Perform association analysis using LinkFinder
• Select the cancer cohort: CPTAC_UCEC
• Select search dataset : Clinical Data type
• Optional, Select population [do not select in this example]
• Select attribute/phenotype of interest: Serous
• Select target dataset with which possible pair-wise
association analyses will be calculated: HiSeq RNA Data Type
(gene level)
• Select statistical method: T-test
• Click SUBMIT QUERY
CPTAC Training, NIH 2018
Lets explores more cases
• Case example: JAK1 protein association with other proteins
Perform association analysis using LinkFinder
• Select the cancer cohort: CPTAC_UCEC
• Select search dataset : Proteome
• Optional, Select population [do not select in this example]
• Select attribute/phenotype of interest: JAK1
• Select target dataset with which possible pair-wise
association analyses will be calculated: Proteome
• Select statistical method: Pearson
• Click SUBMIT QUERY
• LinkInterpreter
• Select GSEA
• Select WikiPathway
• view Significant enrichment and Map
CPTAC Training, NIH 2018
Lets explores more cases
• Case example: AKT1 phosphpoprotein association with other
phosphoproteins expression
Perform association analysis using LinkFinder
• Select the cancer cohort: CPTAC_UCEC
• Select search dataset : Phosphoroteome
• Optional, Select population [do not select in this example]
• Select attribute/phenotype of interest: AKT1
• Select target dataset with which possible pair-wise
association analyses will be calculated: Phosphoroteome
• Select statistical method: Spearman
• Click SUBMIT QUERY
• LinkInterpreter
• Select GSEA
• Select TF pathway
• view Significant TFs
CPTAC Training, NIH 2018
Compare “Concordance” or “Discordance” among or across cancer omics platform
LinkCompare
CPTAC Training, NIH 2018
Click to Compare
Compare serous association in RNAseq and
Proteomics
CPTAC Training, NIH 2018
Results shown in Table with metaSignificance
value
CPTAC Training, NIH 2018
Result comparison and visualization
18 54
Proteome RNAseq Proteome RNAseq
CPTAC Training, NIH 2018
Significant genes in both platforms
CPTAC Training, NIH 2018
Thank You
for
Joining session

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CPTAC3_NIH_Workshop_05012018.pptx

  • 1. CPTAC Training, NIH 2018 LinkedOmics: A web-based platform for cancer multi-omics data analysis, integration and comparison 01/05/2018 Suhas Vasaikar suhas.vasaikar@bcm.edu Dr. Bing Zhang Group Baylor College of Medicine, Houston Texas CPTAC WORKSHOP
  • 2. CPTAC Training, NIH 2018 Multidimensionality of high-throughput data Experimental Study GEO data Public OMICS resource PDX Samples Is data accessible? Is public data available in the usable format ? With the use of available data, how to understand the relation between tumor-associated attributes in different platforms ? How to perform across platform analysis ? TCGA Cancer cohort Increase in dimensionality increases complexity
  • 3. CPTAC Training, NIH 2018 www Multi-Omics Analysis (Why and How?) Challenge is how to make genomic/proteomic data available to user and allow them to perform multi-omics / pan-cancer analysis without difficulty
  • 4. CPTAC Training, NIH 2018 Platforms /MS proteomics Clinical Methylation Mutation CNV mRNA RPPA Proteomics miRNA Mutation Copy number Gene expression DNA methylation microRNA RPPA/MS proteomics Clinical data Discover, compare, and interpret omics associations mRNA Copy number Protein Protein 1 Protein 2 Protein 3 …… …… …… …… …… …… …… …… Protein n mRNA Protein LinkedOmics Motivation TCGA Pathway
  • 5. CPTAC Training, NIH 2018 Omics data for 32 cancer cohorts downloaded from TCGA (version 2016_01_28). The platform includes data from methylation (gene level), copy number variation (focal and gene level), mutation (site and gene level), mRNA expression (gene level), miRNA expression (gene level), RPPA (analyte and gene level) and clinical data (phenotype) related to primary tumors from 11,158 patients. It also includes mass spectrometry-based proteomics data generated by the Clinical Proteomic Tumor Analysis Consortium (CPTAC) for TCGA breast, colorectal, and ovarian tumors. Data Source
  • 6. CPTAC Training, NIH 2018 LinkFinder Within- and cross-omics associations LinkCompare Multi-omics and pan-cancer analysis LinkInterpreter Pathway and network analysis LinkInterpreter Pathway and network analysis LinkFinder Within- and cross-omics associations LinkCompare Multi-omics and pan-cancer analysis TCGA/ CPTAC LAML, ACC, BLCA, LGG, BRCA, CESC, CHOL, COAD, COADREAD, ESCA, GBM, HNSC, KICH, KIRC, KIRP, LIHC, LUAD, LUSC, DLBC, MESO OV, PAAD, PCPG, PRAD, READ, SARC, SKCM STAD, TGCT, THYM, THCA, UCS, UCEC, UVM 32 cancer types; 11,158 patients; >1 billion data points Data Organization and Analysis Modules
  • 7. CPTAC Training, NIH 2018 Webportal www.linkedomics.org
  • 8. CPTAC Training, NIH 2018 www.linkedomics.org Overview of “LinkedOmics” webportal Query Panel has 5 steps Step1: Select Cancer Type Step2: Select Search dataset, for ex. Mutation datatype Step2b: Select Specific Population (optional) Step3: Select Search attribute, for ex. TP53 Step4: Select Target dataset, for ex. mRNA Expression (RNAseq) datatype Step5: Select Statistical Method Click 'SUBMIT' button
  • 9. CPTAC Training, NIH 2018 Lets explores some examples
  • 10. CPTAC Training, NIH 2018 In Prospective Uterine Corpus Endometrial Carcinoma (UCEC), how clinical phenotype serous associated with gene expression? Example1 Search Dataset Target Dataset Search Attribute Cancer cohort
  • 11. CPTAC Training, NIH 2018 Select the cancer cohort “CPTAC UCEC”
  • 12. CPTAC Training, NIH 2018 Select “Search attribute” and “Target Dataset”
  • 13. CPTAC Training, NIH 2018 Select “Statistical test”
  • 15. CPTAC Training, NIH 2018 Serous phenotype associated with gene expression View Results Search history will be shown New analysis to START
  • 16. CPTAC Training, NIH 2018 Serous phenotype associated with gene expression
  • 18. CPTAC Training, NIH 2018 LinkInterpreter Enrichment analysis
  • 21. CPTAC Training, NIH 2018 Lets explores more cases • Case example: Clinical Serous phenotype association with Proteomics Perform association analysis using LinkFinder • Select the cancer cohort: CPTAC_UCEC • Select search dataset : Clinical Data type • Optional, Select population [do not select in this example] • Select attribute/phenotype of interest: Serous • Select target dataset with which possible pair-wise association analyses will be calculated: HiSeq RNA Data Type (gene level) • Select statistical method: T-test • Click SUBMIT QUERY
  • 22. CPTAC Training, NIH 2018 Lets explores more cases • Case example: JAK1 protein association with other proteins Perform association analysis using LinkFinder • Select the cancer cohort: CPTAC_UCEC • Select search dataset : Proteome • Optional, Select population [do not select in this example] • Select attribute/phenotype of interest: JAK1 • Select target dataset with which possible pair-wise association analyses will be calculated: Proteome • Select statistical method: Pearson • Click SUBMIT QUERY • LinkInterpreter • Select GSEA • Select WikiPathway • view Significant enrichment and Map
  • 23. CPTAC Training, NIH 2018 Lets explores more cases • Case example: AKT1 phosphpoprotein association with other phosphoproteins expression Perform association analysis using LinkFinder • Select the cancer cohort: CPTAC_UCEC • Select search dataset : Phosphoroteome • Optional, Select population [do not select in this example] • Select attribute/phenotype of interest: AKT1 • Select target dataset with which possible pair-wise association analyses will be calculated: Phosphoroteome • Select statistical method: Spearman • Click SUBMIT QUERY • LinkInterpreter • Select GSEA • Select TF pathway • view Significant TFs
  • 24. CPTAC Training, NIH 2018 Compare “Concordance” or “Discordance” among or across cancer omics platform LinkCompare
  • 25. CPTAC Training, NIH 2018 Click to Compare Compare serous association in RNAseq and Proteomics
  • 26. CPTAC Training, NIH 2018 Results shown in Table with metaSignificance value
  • 27. CPTAC Training, NIH 2018 Result comparison and visualization 18 54 Proteome RNAseq Proteome RNAseq
  • 28. CPTAC Training, NIH 2018 Significant genes in both platforms
  • 29. CPTAC Training, NIH 2018 Thank You for Joining session