ITCR Collaboration Supplement Rachel Karchin, Mike Ryan, Shirley Liu, Aviv Regev, Brian Haas, Mary Goldman, David Haussler, Jing Zhu UCSC Xena CRAVAT/MuPIT
TCGA, ChIP-seq Annotated Xena Cistrome RNA-Seq LINCS, Data Transcriptome Browser Analytics Data … Browser Xena Trinity Cistrome Cravat/ MuPIT CRAVAT Annotation & Mutations Visualization
TCGA, ChIP-seq Annotated Xena Cistrome RNA-Seq LINCS, Data Transcriptome Browser Analytics Data … Browser Xena Trinity Cistrome Scores TCGA 3D Visualization Data Mutations Annotations CRAVAT Driver Scores 3D Visualization Mutations Cravat/ MuPIT CRAVAT Annotation & Mutations Visualization
TCGA, ChIP-seq Annotated Xena Cistrome RNA-Seq LINCS, Data Transcriptome Browser Analytics Data … Browser Xena Trinity Cistrome Scores TCGA 3D Visualization Data Mutations Annotations CRAVAT Driver Scores 3D Visualization Mutations Cravat/ MuPIT CRAVAT Annotation & Mutations Visualization
CRAVAT/MuPIT http://cravat.us/ High-throughput services to annotate and prioritize variants and genes. Annotations Features Mappings Algorithms Parallel Processing Server
CRAVAT/MuPIT Funnel can be tailored to user needs
Example of funnel developed for familial pancreatic cancer (FPC) WGS study well-known FPC genes Genetic basis of FPC unknown for 80-90% of patients • Analysis of 70M SNVs identifies new genes not previously • implicated in FPC susceptibility
CRAVAT/MuPIT interactive variant view select from 31 TCGA cancers, mutations from UCSC Xena
CRAVAT/MuPIT interactive gene view
CRAVAT / MuPIT ITCR Integration Supplement • Discussions with other ITCR tools showed need for multiple ways of integrating with CRAVAT/MuPIT to maximize use of our services: – Fast method of getting score and annotations for a single genomic location. – Asynchronous processing of full batch of input mutations. – Galaxy support needed – Simple method for other web tools to show MuPIT visualizations of their mutation in annotated 3D structures. – Cross platform support needed – request from other web servers, Java, Python, etc.
Developed - CRAVAT Web Service Fast, Cross-platform single mutation lookup Precomputed VEST Scores (Mutation Pathogenicity) HTTP Request (genomic location) Program / Web Server JSON Reply with: Driver VEST Score Genes Mutation Impact Annotations Cancer Annotations Population Stats Dark CRAVAT / MuPIT Mapability Warnings Regions Web Server COSMIC 1000 ESP6500 ExAc DB SNP Genome
Developed - CRAVAT RESTful Service Method for automated submission of large sets of mutations SNVBox Precomputed Genomic Features HTTP Post Request (file of mutations) CRAVAT / VEST Algorithms Program / HTTP Status Check Pipeline Driver Genes Results File - CHASM and VEST Scores Annotations - Full set of annotations Dark CRAVAT / MuPIT Regions Web Server COSMIC 1000 ESP6500 ExAc DB SNP Genome
Developed MuPIT HTTP Link Integration Get MuPIT 3D Mutation Visualization with URL with genomic location or gene HTTP URL External Web Page HTML / Javascript Visualization Page MuPIT / PDB Database CRAVAT / MuPIT Web Serverr
Developed Galaxy Integration CRAVAT tool in Galaxy Toolshed – VEST Scores and Annotations for Mutations
TCGA, ChIP-seq Annotated Xena Cistrome RNA-Seq LINCS, Data Transcriptome Browser Analytics Data … Browser Xena Trinity Cistrome Scores TCGA 3D Visualization Data Mutations Annotations CRAVAT Driver Scores 3D Visualization Mutations Cravat/ MuPIT CRAVAT Annotation & Mutations Visualization
Trinity CTAT Mutation Pipeline Collaborations Overview
Trinity CTAT Mutation Pipeline Collaborations Overview Access to supercomputing resources from your laptop!
Trinity CTAT Mutation Pipeline Collaborations Overview Transparent integration to CRAVAT web services.
Trinity CTAT Mutation Pipeline Collaborations Overview Custom visualization is a product of multiple labs efforts.
Sample Visualization is a Collection of Collaborations
Sample Visualization is a Collection of Collaborations IGV
Sample Visualization is a Collection of Collaborations CRAVAT
Sample Visualization is a Collection of Collaborations NCGAS
Sample Visualization is a Collection of Collaborations
Exploring a Single Variant
Exploring a Single Variant IGV
Exploring a Single Variant CRAVAT
Exploring a Single Variant MuPIT
Exploring a Single Variant
MuPIT Provides Additional Context Visualize variants within protein structure.
TCGA, ChIP-seq Annotated Xena Cistrome RNA-Seq LINCS, Data Transcriptome Browser Analytics Data … Browser Xena Trinity Cistrome Scores TCGA 3D Visualization Data Mutations Annotations CRAVAT Driver Scores 3D Visualization Mutations Cravat/ MuPIT CRAVAT Annotation & Mutations Visualization
Cistrome Analysis Pipeline Functions • ChIP-chip / seq peak calling • Checking corr and overlap • Visualize signal across different elements • Conservation analysis • Lift over from one genome to another • Annotate target genes • Motif analysis • Heatmap and clustering of many factors • Gene expression microarray analysis • Examine factor function and collaborators • Compatible with Genome Space Liu et al, Genome Biol 2011; > 6000 users, 64TB of data 32
Cistrome Dataset Browser 33
RABIT Integration framework Key features : 1, Control tumor confounding factors (CNA, Methylation) 2, Test ENCODE cell line match with TCGA cancer types RABIT framework
XENA: visualization RABIT collaborate
RABIT -> Xena <- Cistrome RABIT SPI1 SPI1 target regulatory We host the RABIT results genes SPI1 impact on main UCSC public hub From RABIT along with all other Level 2+ TCGA data, such as gene expression. From TCGA Samples n-500 RABIT t-test value indicates the regulatory potential of a specific transcription factor (TF) in a tumor TF up-regulates its target genes TF does not regulate its target genes TF down-regulates its target genes Cistrome Identified SPI1 ChipSeq Target
RABIT -> Xena RABIT SPI1 regulatory Tumors where SPI1 impact down-regulates its target genes (low p-value = 0.00022 score) are associated with poor survival in TCGA Kidney Clear Cell Carcinoma Samples (KIRC). 1 [1] Jiang P, et. al.. Inference of transcriptional regulation in cancers. Proc Natl Acad Sci U S A. 2015 Jun 23; 112(25):7731-6.
Linc-RNA super enhancer curation from histone mark ChIP-seq
Linc-RNA promoter annotation and Trinity collaboration Waiting for linc-RNA analysis result from Trinity
TCGA, ChIP-seq Annotated Xena Cistrome RNA-Seq LINCS, Data Transcriptome Browser Analytics Data … Browser Xena Trinity Cistrome Scores TCGA 3D Visualization Data Mutations Annotations CRAVAT Driver Scores 3D Visualization Mutations Cravat/ MuPIT CRAVAT Annotation & Mutations Visualization
UCSC Xena System Xena Hub Hosts functional genomics data. API access. ICGC Easily deployable: MAC, Windows, TCGA Linux, Amazon cloud CCLE Xena Browser Web-based data access and visualization across multiple Xena hubs. Integrated with Galaxy UCSC Treehouse Childhood Xena Connect to many other bioinformatics Cancer tools, including mutation callers, clustering algorithms, etc. Your private data xena.ucsc.edu
Visualize data from two Xena Hubs on a web browser Every row is a sample, 467 samples From private Xena From main, public Xena Hub Hub on laptop
UCSC Xena Main Data Hub • ICGC (release 19) – 42 cohorts, plus ICGC Pan-Cancer data • TCGA (level 2+) – 34 cancer types, plus TCGA Pan-Cancer data • Pediatric Cancer – St. Jude PCGP, TARGET, Treehouse etc • Cell Line data
Supported data types ● Mutation: SNPs and small INDELs ● Gene, Exon, miRNA, Protein expression (-seq or Array-based) ● Copy Number ● DNA Methylation ● Phenotype/Clinical data: e.g. subtype, tumor type, age
Somatic Mutation Analysis CRAVAT -> Xena -> MuPIT
CRAVAT -> Xena -> MuPIT CDKN2A PIK3CA KDM6A ARID1A STAG2 RHOB TP53 TSC1 ELF3 RB1 Xena gene-level somatic mutation heatmap: Top 10 mutated genes (MutSig) in TCGA Bladder Cancer Cohort Samples (n=437) Samples (n=437) Gene harbors any non-silent mutation Gene does not harbor a non-silent mutation
CRAVAT -> Xena -> MuPIT CRAVAT RHOB RHOB variant mutation allele driverness Xena displays location frequency score CDKN2A RHOB mutations PIK3CA KDM6A ARID1A STAG2 RHOB TP53 TSC1 ELF3 RB1 on transcript. Transcript model along top. Mutations ordered by position on the transcript. CRAVAT driverness score added by user. Samples Samples VAF 100% q value 0 VAF 0% q value 0.5
CRAVAT -> Xena -> MuPIT CRAVAT RHOB RHOB variant mutation allele driverness location frequency score Single click transfers mutations in Xena to MuPIT 3D- view Samples VAF 100% q value 0 VAF 0% q value 0.5
Recommend
More recommend
