Keynote: Trey Ideker - New Challenges and... - ISMB/ECCB Stockholm 2009

Trey Ideker has an impressed career. He obtained his PhD in 2001, now at UCSD - Diego M. Riaño-Pachón

The curse of systems biology: you will be a jack of all trades, rather than a master of one. - Allyson Lister

How does one automatically model systems and pathways from a variety of data - Oliver Hofmann

Ideker et al.: Ann Rev Genomics Hum Genetics 2001 - his PhD work (Systems Biology: A new approach to decoding life. - Allyson Lister

Given basic knowledge of a pathway measure the global response to systematic perturbations, compare predictions and observations and determine the goodness of fit, revise and repeat - Oliver Hofmann

Ideker (Sciene 2001), GAL metabolic flow as an example - Oliver Hofmann

Use systematic interaction data (Protein-DNA, PPI, biochemical reactions) to zoom out from a well-understood small pathway to a more global view - Oliver Hofmann

The final figure of that Science manuscript, he feels, launched his career. - Allyson Lister

Change to the 'modern area'. Querying large biological networks for active modules, colouring graphs with expression states, enzyme activity, any kind of activity. Automatically extract subnetworks / modules from the global 'hairball' - Oliver Hofmann

Interaction Database Dump, aka "Hairballs", which aren't good for a whole lot. - Allyson Lister

Projection of siRNA phenotypes on a HIV protein interaction network (human-human and human-HIV) to identify active modules - Oliver Hofmann

For what @Oliver said directly above: (Konig et al. Cell 2008). - Allyson Lister

A working map for moving network biology to the clinic: does not have to be complete and can tolerate false positives. Innovation in how to assemble the map (what pieces / input) - Oliver Hofmann

Key problem: moving past the pretty pictures and interpreting them - Oliver Hofmann

The cell is actually a hairball - Diego M. Riaño-Pachón

What else can we do with these network maps, for example in human health and disease? - Lucas Brouwers

Path- and NetworkBLAST for cross-comparison of networks. Apply techniques that work well for genomes and apply them to networks - Oliver Hofmann

Looking for matched protein pairs (by sequence similarity) with conserved interactions between species - Oliver Hofmann

Human vs mouse TF-TF networks in brain (Tim Ravasi) - Allyson Lister

Using the FANTOM4 data - Oliver Hofmann

Subsets of tissues with perfect alignment of TF subnetworks - Oliver Hofmann

Sharan & Ideker. Nat Biotech 2006 - Diego M. Riaño-Pachón

What follows is a very nice slide on the timeline of both biological sequence comparison and biological network comparison. Can't write that! See @Diego above for citation for this - Allyson Lister

Trey thinks there are better things out there now than PathBLAST and networkBLAST. - Allyson Lister

Genetic interactions form a distinct type of network maps. Comparison across network types instead of across species - Oliver Hofmann

Here, there exists a genetic interaction between gene A and B if phenotype of mutant a is OK, mutant b is OK, and mutant ab is sick. (Tong et al. Science 2001) - Allyson Lister

Identify biological pathways / physical interactions that support genetic interactions - Oliver Hofmann

Kelley and Ideker Nat Biotech 2005 worked on systematic identification of parallel pathway relations. - Allyson Lister

Genetic interactions run 'between' clusters of physical interactions, not within them - Oliver Hofmann

(Kelley and Ideker, Nat Biotech 2005) - Oliver Hofmann

Results in a functional map of protein complexes linked by 'bundles' of genetic interactions between complexes - Oliver Hofmann

(Roguev, Science 2008) Genetic interaction maps are conserved between species (S cerevisiae, S pombe) - Oliver Hofmann

http://www.cytoscape.org - Diego M. Riaño-Pachón

Change of networks and methods again: ChIP-chip to integrate cause-and-effect networks with physical networks - Oliver Hofmann

TF-promoter binding, PPI and effect of perturbation on expression (regulation) - Oliver Hofmann

"If you have a problem with [Cytoscape], please, don't change software; just join us". - Chad Davis

(Yeang, Mak, Genome Biol 2005) - Oliver Hofmann

What if a lot of transcriptional binding is real but inconsequential to cellular function? - Allyson Lister

What if a binding event is real but inconsequential to the cell? - Diego M. Riaño-Pachón

Results of the method in Workman, Mak, Science 2006 - Oliver Hofmann

K/O TFs and look at expression data to help identify real and functional binding - Cass Johnston

This is a great keynote: it's like a review article in presentation form (plus more)! - Allyson Lister

Over 90% of ChIP-chip interactions not significant in the combined network - Oliver Hofmann

around 90% of the binding events (ChIP-chip) appear to be inconsequential to the cell - Diego M. Riaño-Pachón

the remaining 10% is very significant, more than expected by chance - Diego M. Riaño-Pachón

Physical location of TFs: subset exhibits bimodal chromosomal localization, enriched in the subtelomeric regions - Oliver Hofmann

Gal4 among them - Diego M. Riaño-Pachón

Regions are enriched for stress genes. Binding of factors to the region seems to be condition-specific - Oliver Hofmann

Factors being sequestered away from their target genes under certain conditions? - Oliver Hofmann

Network-based disease diagnosis and prognosis - Oliver Hofmann

Changes to a breast cancer metastasis classifier using additional features. (Imperfect) diagnostic sets of genes have been identified previously, ROC at around 0.65 - Oliver Hofmann

Lack of robustness across studies (overlap between three classifier sets not larger than random expected overlap) - Oliver Hofmann

Overlay with PPI data to identify informative subnetworks (Chuang, Mol Sys Biol 2007) - Oliver Hofmann

Taylor et al. 2009 Nat Biotech, better approach recommended by Trey - Diego M. Riaño-Pachón

blog post: http://themindwobbles.wordpress.com/2009... - Allyson Lister

Thank you for the notes. Allyson - Kuan-Ting Lin

@Kuan-Ting no problem at all! Me and the other bloggers enjoy making them! - Allyson Lister