Interplay of TFs with Chromatin

The internal structure of the nucleus is complex. It is packed with assorted molecules all trying to work together to execute cellular function. The interplay of nuclear components such as transcription factors and nucleosomes is likely more complex than previously anticipated. A recent paper by Lam, Steger, and O’Shea beings to highlight that complexity. But first, the a little back story ….

Analogy

A relatively recent read of Yu and Gerstein’s 2006 PNAS paper has got me thinking about analogies and metaphors in biological networks. As Yu points out, protein-protein interaction networks have frequently been compared to social communication networks … sharing characteristics such as small-world and scale-free properties. Yu presents a plausible analogy between transcriptional regulatory networks and organizational control structures (in other words, a form of bureaucracy). The difference, as Yu states is, “more oriented towards control than communication.”

I’ve been reading and thinking quite a bit lately about biological networks with respect to genetic interactions such as synthetic lethal (& synthetic sick), rescue, and dosage compensation. Oversimplifying, in all these cases the network is able to adjust to perturbation … sometimes in, as of yet, unpredictable fashion. The buzz words here are redundancy and robustness. A decent analogy already exist in this arena. Primarily associated with metabolic networks, the pipe analogy represents the pathways through the network as pipes which flow metabolites to reach some final destination. So a perturbation is effectively a disruption to a pipe. For robustness you depend on some other pipe in the system to pick up the load.

Nurse’s commentary

I thought I’d comment on Paul Nurse’s recent commentary in Nature, but Alex Palazzo over at The Daily Transcript beat me to the punch. He’s got a great piece on the topic.

Yeast Genetics and Molecular Biology 2008

The Yeast Genetics and Molecular Biology Meeting 2008 was held in Toronto. There is a tremendous amount of quality research going on within the yeast community. Given that I was also in Toronto to attend the ISMB meeting, which overlapped, I wasn’t able to attend several sessions. That said, my highlights from the 2008 Yeast Meeting:

• New method of protein-protein interaction detection called protein-fragment complementation (PCA) looks promising (Landry et al).
• The entire session on EvoDevo (Saturday morning) was excellent:
  • Kevin Verstrepen’s work on repeat analysis both within and between genes looks interesting and I look forward to this paper (Smukalla et. al. — under review).
  • Ivan Liachko gave a nice talk on their comparative functional analysis of the origin of replication in related yeast species. The picture emerging is a elegant story of evolutionary change.
  • There were a couple great talks from labs using chemostats to really go after the process of evolution. I particularly liked Maitreya Dunham’s talk on cerevisiae and bayanus hybrids.
• Tim Hughes and Cong Zhu gave back-to-back talks on their efforts to catalog the complete set of sequence preferences for all transcription factors in yeast. This is tough work, especially when the field can’t even agree on the starting point (what is the complete list of transcription factors in yeast?). However, once complete, their efforts will make an enormously useful dataset.
• Based on talks from the 454 and ABI Solid representatives, it’s only a matter of months before the $1000/genome is a reality in the yeast world. With 454’s long reads, they seem (currently) to be the right way to go after de novo genomes.
• Based on the myriad of posters and talks on assorted genes in yeast … pleiotrophy is the rule, not the exception. Some of the functions can be attributed to specific domains within the protein. Others are more a consequence of the way cellular networks interconnect. Finally, some functions only seem to arise when needed … in essence, a backup when something elsewhere goes wrong.

ISMB 2008

The 16th Annual International Conference on Intelligent Systems for Molecular Biology (ISMB 2008) was held in Toronto in late July this year. The Conference Proceedings are available from Bioinformatics (subscription required). Except during keynotes, there were as many as 7 parallel sessions going simultaneously … Proceedings talks (new work), Highlights talks (previously published work), special interest groups (SIGs), special sessions (mini SIGs), technology and industry sessions. Luckily, a group of attendees blogged the conference providing a live account and notes on numerous sessions.

The parallel SIG entitled “Post-ENCODE” contained numerous good talks, mostly on work which has largely already been published. The gem talk of the SIG was when James Taylor explored the open questions and lead a directed discussion on the implications of ENCODE for computational modeling.

Other highlights from ISMB 2008 include:

• Sinha’s talk on their efforts to build better models of regulatory modules at different evolutionary distances. His lab is clearly doing very impressive work.
• Royer’s talk on their use of power graphs to summarize the assorted large scale network results. This work was recently published in PLoS Comp. Biol and looks very promising.
• Brett Tyler gave a nice talk (in the special session entitled “Computational Challenges and Opportunities in Host-Pathogen Systems Biology”) on their very preliminary efforts to integrate genetic information with infection time-series expression analysis.
• The best session was the four talks in the Hall G Highlights session Wednesday Morning. In all four talks solid modeling techniques were utilized to tackle key problems: Holmes on Transducers as models of indel (and RNA) evolution; Yeang on his co-evolutionary model; Noble on nucleosome positioning; and Backofen on structural ncRNAs.

Finally, the Birds of a Feather session on Science blogging has made their notes from the session available from Google Docs. The same group of people leading the live blogging (FriendFeed) were behind this BFF session.