1. Network integration and function prediction: Putting it all together Slides courtesy of Curtis Huttenhower 04-13-11 Harvard School of Public Health Department of Biostatistics

2. A computational definition of functional genomics 2 Genomic data Prior knowledge Data ↓ Function ↓ Function Gene ↓ Gene ↓ Function

3. A framework for functional genomics 3 High Similarity Low Similarity High Correlation Low Correlation G1 G2 + G4 G9 + … G3 G6 - G7 G8 - … G2 G5 ? 0.90.7…0.10.2…0.8 +-…--…+ 0.5…0.050.1…0.6 High Correlation Low Correlation Frequency Coloc.Not coloc. Frequency SimilarDissim. Frequency P(G2-G5|Data) = 0.85 100Ms gene pairs → ← 1Ks datasets + =

4. MEFIT: A Framework for Functional Genomics 4 Golub 1999 Butte 2000 Whitfield 2002 Hansen 1998 Functional Relationship Biological Context Functional area Tissue Disease …

5. Functional network prediction and analysis 5 Global interaction network Metabolism networkSignaling networkGut community network Currently includes data from 30,000 human experimental results, 15,000 expression conditions + 15,000 diverse others, analyzed for 200 biological functions and 150 diseases HEFalMp

6. HEFalMp: Predicting human gene function 6 HEFalMp

7. HEFalMp: Predicting human genetic interactions 7 HEFalMp

8. HEFalMp: Analyzing human genomic data 8 HEFalMp

9. HEFalMp: Understanding human disease 9 HEFalMp