PCBC Bioinformatics Core & Committee PCBC Steering Committee Call Nathan Salomonis Cincinnati Children’s Larsson Omberg, Sage Bionetworks Nathan Salomonis Division of Biomedical Informatics, CCHMC

Bionformatics Working Group Bruce Aronow Nathan Salomonis Phillip Dexheimer Carolyn Lutzko Alex Pico Larsson Omberg Kenny Daily Antonis Hatzopoulos Winston Hide Shanan Sui Joseph Huo Elias Zambidis Michael Kyba Jennifer Larkin Lynn Schriml Michael Terrin Ling Tang * * * * * * * * * * * * * C4 SAGE BIONETWORKS VANDERBILT U. HARVARD U. JOHNS HOPKINS U. USCF STANFORD U. U. MINNESOTA NHLBI ADMINISTRATIVE CORE U. MARYLAND

PCBC Bioinformatics Committee & Core Create structured annotations for iPSC generation and derived products (metadata). Provide new tools and resources for access to analysis of C4 data. Provide education to the PCBC and beyond. Spearhead informatics efforts in the consortium.

Prior Progress on Primary Aims Developed Metadata standards for cell lines Developed an advanced online portal in Synapse for direct access to: –PCBC omics datasets –Integrated analysis results –Metadata –Protocols (experimental, software) –Other datasets Created specialized tools for PCBC data access: –ToppGene progenitor signatures (pathway analysis) –Cytoscape tool for Synapse data visualization –AltAnalyze for integrated omics analyses and progenitor cell-type prediction Collaboratively wrote papers for description of these resources and datasets.

Major Updates PCBC Omics Portal is Live (Stealth Release). Resubmitting manuscript 1 following Cell Stem Cell encouraging reviews. Multitude of new interfaces, automated worfklows, result sets in Synapse. Significant progress on differentiation manuscript analyses. New software to help experimentalists analyze their own omics data. Recent and future bioinformatics workshops.

Synapse: Online repository for PCBC data access, annotations, sharing and analysis Online repository for PCBC data access, annotations, sharing and analysis.

Key Features of Synapse Download PCBC Omics data from the web or programmatically (R/Python/Java). Easily post new datasets, images or presentation. “Time Machine” of Data Files and Analyses. Access Control – Private Work Areas. DOI Annotation for Direct Data Access from Publications. Wiki Content – Editing Help Desk

Target Audiences of PCBC Database in Synapse Investigators Explore Genes/Pathways Explore Processing Pipelines Genes/Pathways Search Engines Review Results of Previous Analyses Communicate Early Results Share Results Target Audiences of PCBC Database in Synapse

Target Audience Bioinformaticians Process Own Data Using Defined pipelines Download & Query Raw data Access directly from R/Python/JAVA Download Analysis Results Share analysis Target Audience

Navigate PCBC Data: Download, Query, perform Pathway Analysis

Target Audience Follow Data Pipelines with Own Experimental Results Private Work Areas

Target Audience Collaborate with Other Groups Collaborative Private Work Areas

Usage Over 300 users outside of the bioinformatics core. –111 registered PCBC users accessing the site. –200 folks outside of the PCBC

Usage

Brand New Features in Synapse PCBC Portal is open-access to anyone with a free Synapse account ( March 2015 – stealth release prior publication ). New and Improved heatmap viewer with integrated RNA- Seq, DNA-methylation and microRNA. Simple interactive metadata navigator for cell lines (to be updated with Wicell). Amazon hosted virtual computing environment with tools for sequence analysis of any data. Expanded bioinformatics best practices and protocol comparison (tutorial videos, algorithm comparisons, etc.). Improved attribution pages. New analysis methods and results associated with bioinformatics core papers being (re)submitted

PCBC Metadata Developed According to Global Vocabularies of Terms Creating Metadata Standards for Sharing Exchanging and Analyzing PCBC Data How is the PCBC Metadata Standard Organized ? - categories of metadata - describing cell line, host and classification methods -including investigator, cell of origin, method of reprogramming, -reprogramming gene combinations, donor gender, age, ethnicity and disease status Metadata Collection Standards - developed for the PCBC consortium - defined through an iterative process - relevant terms mapped to established community ontologies - metadata collected for each cell line submitted to C4

Metadata Associated Data mRNA-Seq –301 samples microRNA-Seq –252 samples DNA-methylation –131 samples

PCBC Metadata Developed According to Global Vocabularies of Terms Ontologies: Disease Ontology, NCBI Taxonomy vocabulary, Cell Ontology, Cell Line Ontology, HsapDv (human developmental stage ontology), NCI Thesaurus (race, ethnicity), PATO (gender), Human Phenotype Ontology Tools: PCBC Metadata Developed According to Global Vocabularies of Terms

PCBC Metadata Developed According to Global Vocabularies of Terms PCBC Metadata Annotations as Exchange Format (ISA-Tab) Allow Global Data Sharing/Reuse Document Provenance/History of Data Investigation-Study-Assay (isatab)

New Software for PCBC Researchers We are in the final stages of releasing tools to allow bioinformatics novice researchers to analyze their own bulk and single-cell RNA-Seq datasets (AltAnalyze version 2.10). New tools for cell-type prediction automated within this tool-kit. Used by over a dozen PCBC researchers at the Stanford Bioinformatics training course.

Manuscripts 1.Re-Submission of the first C4 Manuscript (Cell Reports): –Integrated Genomic Analysis of Diverse Induced Pluripotent Stem Cell Lines Identifies Novel Molecular Determinants of Pluripotency 2.Data Descriptor manuscript (Following manuscript 1 acceptance): –Comprehensive Characterization of Diverse Pluripotent Stem Cells from the Progenitor Cell Biology Consortium 3.Expected Submission in September –Multi-Lineage Characterization of Diverse Induced Pluripotent Stem Cells and their Derivatives (collaborative multicenter effort lead by Sage)