Connectivity Map Data and Tools

Hands On

Corey Flynn

cflynn@broadinstitute.org

Bioinformatics Scientist II

Connectivity Map,Golub Lab

Cancer Program

Rajiv Narayan

narayan@broadinstitute.org

Computational Biologist

Connectivity Map,Golub Lab

Cancer Program

follow these slides at

http://coreyflynn.github.io/SoapBox/CMAP_hands_on

LINCS and CMap Overview

LINCS Data Concept

  • perturbations scalable to genome
  • high information content read-outs (e.g. gene expression)
  • inexpensive
  • mechanism to query database

GOAL: A look-up table for functional annotation

  • Given a gene or protein
    • What other proteins have similar cellular effects?
    • What compounds impinge upon its activity?

GOAL: A look-up table for functional annotation

  • Given a small molecule compound
    • What is its mechanism of action?
    • What are all of its effects on cells?
    • Is it unique?

GOAL: A look-up table for functional annotation

  • Given a biological state
    • What protein activities relate to that state?
    • What compound activities relate to that state?

L1000 expression profiling

LINCS Expansion

Current LINCS CMap Dataset

Data Collection

Scan data

Cell lysates are scanned in 384 well plates in the L1000 assay

Bead deconvolution

1000 gene measurements are decovoluted from 500 bead colors

Normalization

Scale profiles based on expected levels of invariant gene sets and adjust to expected distribution

Inference

Use regression models to impute the rest of the transcriptome

Z-score

Compute Z-scores to determine differential expression

Differential Expression

Average between replicates weighted by agreement

Consensus Gene Signatures

Integrate across knockdown signatures targeting the same gene to generate consensus gene signatures

Data Matrix

Assemble signatures into a unified matrix

Data Resources

Sig Tools

Query Tool

Compare one signature to all other signatures in the database looking for connections

Summly Tool

Summarize the results of a query to focus on the most reliable connections

Introspect Tool

Look for consistency in related signatures

Sig Info

Get metadata for signatures

Sig Slice

Make subsets of the data matrix