Richard H. Scheuermann, Ph.D.November 5, 2012

Support for Systems Biology Datain IRD/ViPR - Proteomics

Projects with Host Factor Data

• Four systems biology groups funded by NIAID, including:– Systems Virology (Michael Katze group, Univ. Washington)

• Influenza H1N1 and H5N1 and SARS Coronavirus• statistical models, algorithms and software, raw and processed gene expression data, and

proteomics data– Systems Influenza (Alan Aderem group, Institute for Systems Biology/Seattle Biomed)

• Various influenza viruses• microarray, mass spectrometry, and lipidomics data

• ViPR Driving Biological Projects– Abraham Brass, Mass. General Hospital

• Dengue virus host factor database from RNAi screen – Lynn Enquist / Moriah Szpara, Princeton University

• Deep sequencing and neuronal microarrays for functional genomic analysis of Herpes Simplex Virus

– Richard Kuhn, Purdue University• Metabolomics data of Dengue virus infection of human cells and mosquitos

– Mike Diamond, Washington University• Identification of inhibitory interferon-stimulated genes against flaviviruses and noroviruses using

shRNA knockdown• Determine the mechanism of action of individual inhibitory ISGs

• “Omics” data management (MIBBI vs MIBBI-DB)– Project metadata (1 template)

• Title, PI, abstract, publications– Experiment metadata (~6 templates)

• Biosamples, treatments, reagents, protocols, subjects– Primary results data

• Raw expression values– Data processing metadata (1 template)

• Normalization and summarization methods– Processed data

• Data matrix of fold changes and p-values– Data interpretation metadata (1 template)

• Fold change and p-value cutoffs used– Interpreted results (Host factor biosets)

• Interesting gene, protein and metabolite lists

• Visualize biosets in context of biological pathways and networks• Statistical analysis of pathway/sub-network overrepresentation

Strategy for Handling “Omics” Data

Data Submission Workflows

Study metadata

Experiment metadata

Primary results

Analysis metadata

Processed data matrix

Free text metadataGEO/PRIDE/PNNL/SRA/MetaboLights

ViPR/IRD/PATRIC

Host factor bioset

pointer

submission

submission

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Systems Biology sites

Metadata Submission Template Examples

Host Factor Data

8 Studies To Date

Host Factor Bioset

Transcriptomics => Proteomics

• Metadata fields are largely re-usable, with some exceptions– Exp_sample_template (protein).xls

• Results data differences– Peptide-level and protein-level• IM005_Peptide_normalization_matrix.V2.xlsx• IM005_Protein Normalization matrix.xlsx

– Statistical measures• Results_matrix_ IM005_sig Protein_RM.xlsx

Metadata Field Changes

• GEO GSM ID => Primary Data Archive + Primary Data Archive ID

• Semi-structured Experiment Variable to Structured Experiment Variable– Free text (1 day) => value unit pairs in separate fields

(1/day; 10^4/plaque forming units)• Multiple processed data matrix files– Concatenated IDs separated by (; |)

• Reagents and protocols are different but should not require submission template changes

Normalized Data

• Archive at BRC (standard format?)– Peptide normalized data– Protein normalized data– Results matrix of significant proteins

• BRCs derive bioset lists from results matrix– Handling different significance measures• t-test flag, t-test p-value, g-test flag, g-test p-value,

log10 ratio

Host Factor Bioset

On Deck

• Metabolomics and lipidomics data• Integration of RNA expression, protein

abundance and metabolite abundance• Pathway/network visualization and analysis

Acknowledgement

• Lynn Law, U. Washington• Richard Green, U. Washington• Peter Askovich, Seattle Biomed• Brett Pickett, U.T. Southwestern/JCVI • Jyothi Noronha, U.T. Southwestern• Eva Sadat, U.T. Southwestern• Entire Systems Biology Data Dissemination Task

Force, especially Jeremy Zucker• NIAID (Alison Yao and Valentina DiFrancesco)

Future Development Plans

GOenrichment

Networkvisualization

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